Description of a new tick species, closely related to Amblyomma javanense (Supino, 1897), associated with Varanus bengalensis (Squamata: Varanidae) in Pakistan.

The genus Amblyomma contains the highest percentage of reptile-associated ticks, and comprises approximately nine subgenera. One of these subgenera is Adenopleura, which also encompasses Amblyomma javanense, and its type species Amblyomma compressum. This study describes a new Amblyomma species associated with Bengal monitor lizards (Varanus bengalensis) based on morphology and its mitogenome in Khyber Pakhtunkhwa, Pakistan. Reptiles belonging to different genera were examined for Amblyomma ticks and only the monitor lizard was infested with ticks in the District Bajaur. Collected Amblyomma cf. javanense ticks were analyzed and formally described as a new species. Overall, 57 A. cf. javanense ticks were collected on monitor lizards (4/27) with a 15% prevalence of infestation, 2.1 mean abundance, and 14.3 mean intensity. Ticks comprised males (n = 23, 40%), females (n = 14, 25%) and nymphs (n = 20, 35%), while no larvae were found. BLAST analysis of A. cf. javanense sequences showed the following maximum identities; 98.25% with undetermined Amblyomma species based on 12S rRNA, 96.07% with A. javanense based on 16S rRNA, 99.56% and 90.95% with an Amblyomma sp. and A. javanense, respectively, based on ITS2. Moreover, the mitochondrial genome of A. cf. javanense showed maximum identities of 80.75%, 80.48% and 79.42% with Amblyomma testudinarium, A. javanense, and Amblyomma sp., respectively. The phylogenetic analysis of A. cf. javanense revealed that its 12S rRNA and 16S rRNA are closely related to an Amblyomma sp. and A. javanense, respectively, from Sri Lanka, its ITS2 is closely related to A. javanense from China and an Amblyomma sp. from Sri Lanka, and its mitogenome is closely related to A. javanense and Amblyomma sp. from China. The pairwise distance analysis resulted in divergence of 0-1.71% (12S rRNA), 0-17.5% (16S rRNA), 0-9.1% (ITS2) and 0-20.5% (mitochondrial genome). We also contributed the full-length mitochondrial genome sequence of A. compressum and showed that this species does not share a most recent common ancestor with A. javanense. As the subgenus Adenopleura is paraphyletic, this study could help to understand the systematics and phylogeny of this taxon.

Bee pollen as a food and feed supplement and a therapeutic remedy: recent trends in nanotechnology.

Pollen grains are the male reproductive part of the flowering plants. It is collected by forager honey bees and mixed with their salivary secretions, enzymes, and nectar, which form fermented pollen or "bee bread" which is stored in cells of wax honeycombs. Bee pollen (BP) is a valuable apitherapeutic product and is considered a nutritional healthy food appreciated by natural medicine from ancient times. Recently, BP has been considered a beneficial food supplement and a value-added product that contains approximately 250 different bioactive components. It contains numerous beneficial elements such as Mg, Ca, Mn, K, and phenolic compounds. BP possesses strong antioxidant, anti-inflammatory, antimicrobial, antiviral, analgesic, immunostimulant, neuroprotective, anti-cancer, and hepatoprotective properties. It is used for different purposes for the welfare of mankind. Additionally, there is a growing interest in honey bee products harvesting and utilizing for many purposes as a natural remedy and nutritive function. In this review, the impacts of BP on different organisms in different ways by highlighting its apitherapeutic efficacy are described.

Phytic Acid-Promoted Deposition of Gold Nanoparticles with Grafted Cationic Polymer Brushes for the Construction of Synergistic Contact-Killing and Photothermal Bactericidal Coatings.

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.

Endophytic Fungi-Mediated Defense Signaling in Maize: Unraveling the Role of WRKY36 in Regulating Immunity against Spodoptera frugiperda.

Seed priming with beneficial endophytic fungi is an emerging sustainable strategy for enhancing plant resistance against insect pests. This study examined the effects of Beauvaria bassiana Bb20091317 and Metarhizium rileyi MrCDTLJ1 fungal colonization on maize growth, defence signalling, benzoxazinoid levels and gene expression. The colonization did not adversely affect plant growth but reduced larval weights of Spodoptera frugiperda. Maize leaves treated with M. rileyi exhibited higher levels of jasmonic acid, jasmonoyl-Isoleucine, salicylic acid, and indole acetic acid compared to control. B. bassiana and M. rileyi accelerated phytohormone increase upon S. frugiperda herbivory. Gene expression analysis revealed modulation of benzoxazinoid biosynthesis genes. We further elucidated the immune regulatory role of the transcription factor zmWRKY36 using virus-induced gene silencing (VIGS) in maize. zmWRKY36 positively regulates maize immunity against S. frugiperda, likely by interacting with defense-related proteins. Transient overexpression of zmWRKY36 in tobacco-induced cell death, while silencing in maize reduced chitin-triggered reactive oxygen species burst, confirming its immune function. Overall, B. bassiana and M. rileyi successfully colonized maize, impacting larval growth, defense signalling, and zmWRKY36-mediated resistance. This sheds light on maize-endophyte-insect interactions for sustainable plant protection.

Use of air things radon detector in liquid samples (serum and urine).

This study involved the assessment of 222Rn concentrations in liquid samples (namely serum and urine) obtained from individuals who were smokers and non-smokers across five distinct age groups in the Najaf Governorate of Iraq. The measurements were conducted using a portable digital Air Things device commonly employed for detecting radon gas in residential environments. This device was placed in a container that is placed in liquid samples, which makes it work to capture the existing radon. The mean value of radon concentrations in serum and urine samples for smokers was 5.64 ± 2.80 Bq/m3 and 3.56 ± 2.31 Bq/m3, respectively. While, the mean value of radon concentrations in serum and urine samples for non-smokers was 2.32 ± 0.67 Bq/m3 and 1.61 ± 1.00 Bq/m3, respectively. By comparing the radon concentrations for serum and urine samples with age and smoking groups, the value of P-Value (p < 0.01) was increased significantly statistically. Also, it is found that a positive and good correlation for radon concentrations between serum and urine. Although the levels of radon were found to be under the globally accepted thresholds, the results of 222Rn in all samples of serum and urine in smokers were higher than in non-smokers. Thus, it may be concluded that cigarette smoking is used as a biomarker of the presence of radon gas.

Comparison of Heavy Metals in Urine Samples of Smoker and Non-smoker Persons.

In this study, the concentrations of heavy metals such as cadmium (Cd), chromium (Cr), and lead (Pb) in the two groups of cigarette smokers and non-smokers in five age range groups were measured. Heavy metal concentrations were collected in participants' urine samples and analyzed using atomic absorption spectrophotometry (AAS). The results showed that the concentrations of these metals in the urine of smokers were higher than in non-smoker subjects. The mean concentration of Cd, Cr, and Pb for smokers were 1.188 ± 0.931, 1.929 ± 0.940, and 0.069 ± 0.023, respectively, while the mean concentration of Cd, Cr, and Pb for non-smokers were 0.151 ± 0.165, 0.203 ± 0.218, and 0.037 ± 0.030, respectively. The results revealed statistically significant differences when comparing the samples of smokers to the control group in all heavy metals in the present study. Also, the results revealed statistically significant differences in Cd, Cr, and Pb when comparing the samples of smokers to age groups. The trend of metals in urine samples in two groups (smokers and non-smokers) is as follows: Cd > Cr > Pb. The concentration of Cd, Cr, and Pb in all samples of the present study was higher than the biological limit, according to ACGIH. Therefore, Cd, Cr, and Pb were the most critical metals accumulated in the urine of cigarette smokers.

The influence of zwitterionic and anionic phospholipids on protein aggregation.

The progressive aggregation of misfolded proteins is the underlying molecular cause of numerous pathologies including Parkinson's disease and injection and transthyretin amyloidosis. A growing body of evidence indicates that protein deposits detected in organs and tissues of patients diagnosed with such pathologies contain fragments of lipid membranes. In vitro experiments also showed that lipid membranes could strongly change the aggregation rate of amyloidogenic proteins, as well as alter the secondary structure and toxicity of oligomers and fibrils formed in their presence. In this review, the effect of large unilamellar vesicles (LUVs) composed of zwitterionic and anionic phospholipids on the aggregation rate of insulin, lysozyme, transthyretin (TTR) and α- synuclein (α-syn) will be discussed. The manuscript will also critically review the most recent findings on the lipid-induced changes in the secondary structure of protein oligomers and fibrils, as well as reveal the extent to which lipids could alter the toxicity of protein aggregates formed in their presence.

Assessment of radiological risk associated with thoron gas at primary schools in Al-Najaf city, Iraq.

Children spend considerable time at home and school, so school is likely to be a second source of natural radionuclide exposure after home. This study evaluates the radiological risk associated with thoron gas in the air within the building of one hundred primary schools in Al-Najaf City, Iraq, using a CR-39 detector. The results of the average value of thoron concentration detector, the annual effective dose (AED), Excessive Lifetime Cancer Risk (ELCR) × 10-3, and Lung Cancer Case (LCC) × 10-9 measured in the building of the schools were 7.47 ± 2.85 Bq/m3, 0.03 ± 0.01 mSv/y, 0.11 ± 0.04, and 0.54 ± 0.20, respectively. All the results of indoor thoron were below the global average limit. The results of the radiological survey due to thoron concentrations for studied primary schools suggest that the radionuclides and their radiological hazard indexes in all studied schools in AL Najaf city, Iraq, do not impose a health hazard.

Assessment of Heavy Metals in Biscuit Samples Available in Iraqi Markets.

Baby foods contain these toxic heavy metals which occur naturally or from pollution in the environment. The purpose of this research is to investigate the concentration of heavy metals in the biscuit samples that are commonly used in Iraq as food babies. The concentrations of three metals viz zinc (Zn), lead (Pb), and cadmium (Cd) are measured using atomic absorption spectroscopy (Buck Scientific/USA, 210 VGA). Health risk parameters such as Estimated Daily Intake (EDI), Target Hazard Quotients (THQ), Hazard Index (HI), and Carcinogenic Risk (CR), are determined. The average values of the concentrations of Zn, Pb, and Cd in these samples of biscuits are 0.584 ± 0.099 mg/kg, 0.066 ± 0.008 mg/kg, and 0.205 ± 0.011 mg/kg, respectively, while the average values of HI and CR × 10-6 for all samples are 0.768 ± 0.040 and 1.94 ± 0.25, respectively. On the basis of comparing these elements, the study finds that the average value of Zn is dominating with the highest concentration, followed by Cd, and Pb. This is relied on the statistical examination that revealed a weak correlation and no significance (p > 0.05) in the amounts of these heavy metals in all samples. The concentrations of Cd, in seven samples, are relatively higher than their permissible limits according to FAO/WHO (0.2 mg/kg). Conversely, the concentrations of Zn and Pb are lower than their permissible limits which was 9.4 mg/kg and 0.3 mg/kg, respectively. The values of health risk parameters for Zn, Pb, and Cd for all samples do not surpass their permissible intake limits according to FAO/WHO, Therefore, it is concluded that the overall estimated healthy risk, due to the heavy metals, is safe since it is within the permissible limits; thus, there are no concerns for a baby who consume biscuit consistently daily.

Nanoscale structural characterization of transthyretin aggregates formed at different time points of protein aggregation using atomic force microscopy-infrared spectroscopy.

Transthyretin (TTR) amyloidosis is a progressive disease characterized by an abrupt aggregation of misfolded protein in multiple organs and tissues TTR is a tetrameric protein expressed in the liver and choroid plexus. Protein misfolding triggers monomerization of TTR tetramers. Next, monomers assemble forming oligomers and fibrils. Although the secondary structure of TTR fibrils is well understood, there is very little if anything is known about the structural organization of TTR oligomers. To end this, we used nano-infrared spectroscopy, also known as atomic force microscopy infrared (AFM-IR) spectroscopy. This emerging technique can be used to determine the secondary structure of individual amyloid oligomers and fibrils. Using AFM-IR, we examined the secondary structure of TTR oligomers formed at the early (3-6 h), middle (9-12 h), and late (28 h) of protein aggregation. We found that aggregating, TTR formed oligomers (Type 1) that were dominated by α-helix (40%) and ß-sheet (~30%) together with unordered protein (30%). Our results showed that fibril formation was triggered by another type of TTR oligomers (Type 2) that appeared at 9 h. These new oligomers were primarily composed of parallel ß-sheet (55%), with a small amount of antiparallel ß-sheet, α-helix, and unordered protein. We also found that Type 1 oligomers were not toxic to cells, whereas TTR fibrils formed at the late stages of protein aggregation were highly cytotoxic. These results show the complexity of protein aggregation and highlight the drastic difference in the protein oligomers that can be formed during such processes.

Cholesterol and Sphingomyelin Uniquely Alter the Rate of Transthyretin Aggregation and Decrease the Toxicity of Amyloid Fibrils.

Transthyretin (TTR) is a small tetrameric protein that aggregates, forming highly toxic oligomers and fibrils. In the blood and cerebrospinal fluid, TTR can interact with various biomolecules, phospho- and sphingolipids, and cholesterol on the red blood cell plasma membrane. However, the role of these molecules in TTR aggregation remains unclear. In this study, we investigated the extent to which phosphatidylcholine (PC), sphingomyelin (SM), and cholesterol (Cho), important components of plasma membranes, could alter the rate of TTR aggregation. We found that PC and SM inhibited TTR aggregation whereas Cho strongly accelerated it. The presence of these lipids during the stage of protein aggregation uniquely altered the morphology and secondary structure of the TTR fibrils, which changed the toxicity of these protein aggregates. These results suggest that interactions of TTR with red blood cells, whose membranes are rich with these lipids, can trigger irreversible aggregation of TTR and cause transthyretin amyloidosis.

Predictors requiring special attention to prevent clavicle fracture nonunion: a systematic review of literature.

Background: Clavicle fracture (CF) is the tenth most prevalent fracture, accounting for an annual incidence of 37/10,000. This systematic review highlights the factors contributing to the nonunion union of the clavicular fracture. Method: A systematic search was conducted using three web-based databases up to August 12, 2022, for conducting qualitative analysis. Articles were screened for relevance, and only studies that met inclusion criteria based on PECOS; P (patients): participants diagnosed with clavicular fracture; E (exposure): nonunion, C (control): not applicable; O (outcomes): factors contributing to nonunion or delayed union; S (studies): trials and observational studies. The Newcastle-Ottawa Scale was used to assess the quality of the cohort studies. The Cochrane risk of bias tool was used to assess the bias in randomized control trials. Results: Ten studies were selected after the final literature search. Two thousand seven hundred and sixty-six adult participants who were radiologically and clinically diagnosed with nonunion clavicular fracture were included to pool the qualitative results. Fall was the most dominant cause of clavicular fracture, followed by road traffic collisions. Open reduction was widely used to treat nonunion correction. The qualitative results suggested a prominent correlation of nonunion with advancing age, female gender, high energy trauma, high Disabilities of the Arm, Shoulder, and Hand Score, smoking, fracture displacement, clavicular shortening, the callus on radiography, and fracture movement. The mid-shaft fracture was the most dominant type of fracture in the included studies; highly associated with nonunion in comparison to medial or lateral CF. The previous history of operation was an independent factor contributing to nonunion. Conclusion: The results of this systematic review suggested the predictors contributing to nonunion in the CF. Demographic factors such as advancing age with female gender are at higher risk of developing clavicular nonunion. Smoking was the most dominantly highlighted environmental factor contributing to nonunion. Diaphyseal or midshaft fracture was the most common site for nonunion. Therefore, we suggested that patients with the predictors mentioned above require special attention to prevent nonunion of the CFs. More studies should be conducted on this subject to assess the factors that pose a risk associated with the nonunion of the bone for better clinical management and outcomes of the fracture.

Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils.

Transthyretin (TTR) is a small, ß-sheet-rich tetrameric protein that transports thyroid hormone thyroxine and retinol. Phospholipids, including phosphatidic acid (PA), can uniquely alter the stability of amyloidogenic proteins. However, the role of PA in TTR aggregation remains unclear. In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results shed light on the role of PA in the stability of TTR and transthyretin amyloidosis.

Secondary structure and toxicity of transthyretin fibrils can be altered by unsaturated fatty acids.

Transthyretin amyloidosis is a severe pathology characterized by the progressive accumulation of transthyretin (TTR) in various organs and tissues. This highly conserved through vertebrate evolution protein transports thyroid hormone thyroxine. In our bodies, TTR can interact with a large number of molecules, including ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) that are broadly used as food supplies. In this study, we investigated the effect of ω-3 and ω-6 PUFAs, as well as their fully saturated analog, on TTR aggregation. Our results showed that both ω-3 and ω-6 PUFAs strongly decreased the rate of TTR aggregation. We also found that in the presence of PUFAs, TTR formed morphologically different fibrils compared to the lipid-free environment. Nano-Infrared imaging revealed that these fibrils had drastically different secondary structures compared to the secondary structure of TTR aggregates formed in the PUFAs-free environment. Furthermore, TTR fibrils formed in the presence of ω-3 and ω-6 PUFAs exerted significantly lower cell toxicity compared to the fibrils formed in the absence of fatty acids.

Role of Saturation and Length of Fatty Acids of Phosphatidylserine in the Aggregation of Transthyretin.

The progressive accumulation of transthyretin (TTR), a small protein that transports thyroxine, in various organs and tissues is observed upon transthyretin amyloidosis, a severe pathology that affects the central, peripheral, and autonomic nervous systems. Once expressed in the liver and choroid plexus, TTR is secreted into the bloodstream and cerebrospinal fluid. In addition to thyroxine, TTR interacts with a large number of molecules, including retinol-binding protein and lipids. In this study, we examined the extent to which phosphatidylserine (PS), a phospholipid that is responsible for the recognition of apoptotic cells by macrophages, could alter the stability of TTR. Using thioflavin T assay, we investigated the rates of TTR aggregation in the presence of PS with different lengths and saturation of fatty acids (FAs). We found that all analyzed lipids decelerated the rate of TTR aggregation. We also used a set of biophysical methods to investigate the extent to which the presence of PS altered the morphology and secondary structure of TTR aggregates. Our results showed that the length and saturation of fatty acids in PS uniquely altered the morphology and secondary structure of TTR fibrils. As a result, TTR fibrils that were formed in the presence of PS with different lengths and saturation of FAs exerted significantly lower cell toxicity compared with the TTR aggregates grown in the lipid-free environment. These findings help to reveal the role of PS in transthyretin amyloidosis and determine the role of the length and saturation of FAs in PS on the morphology and secondary structure of TTR fibrils.

Silicon Induces Heat and Salinity Tolerance in Wheat by Increasing Antioxidant Activities, Photosynthetic Activity, Nutrient Homeostasis, and Osmo-Protectant Synthesis.

Modern agriculture is facing the challenges of salinity and heat stresses, which pose a serious threat to crop productivity and global food security. Thus, it is necessary to develop the appropriate measures to minimize the impacts of these serious stresses on field crops. Silicon (Si) is the second most abundant element on earth and has been recognized as an important substance to mitigate the adverse effects of abiotic stresses. Thus, the present study determined the role of Si in mitigating adverse impacts of salinity stress (SS) and heat stress (HS) on wheat crop. This study examined response of different wheat genotypes, namely Akbar-2019, Subhani-2021, and Faisalabad-2008, under different treatments: control, SS (8 dSm-1), HS, SS + HS, control + Si, SS + Si, HS+ Si, and SS + HS+ Si. This study's findings reveal that HS and SS caused a significant decrease in the growth and yield of wheat by increasing electrolyte leakage (EL), malondialdehyde (MDA), and hydrogen peroxide (H2O2) production; sodium (Na+) and chloride (Cl-) accumulation; and decreasing relative water content (RWC), chlorophyll and carotenoid content, total soluble proteins (TSP), and free amino acids (FAA), as well as nutrient uptake (potassium, K; calcium, Ca; and magnesium, Mg). However, Si application offsets the negative effects of both salinity and HS and improved the growth and yield of wheat by increasing chlorophyll and carotenoid contents, RWC, antioxidant activity, TSP, FAA accumulation, and nutrient uptake (Ca, K, and Mg); decreasing EL, electrolyte leakage, MDA, and H2O2; and restricting the uptake of Na+ and Cl-. Thus, the application of Si could be an important approach to improve wheat growth and yield under normal and combined saline and HS conditions by improving plant physiological functioning, antioxidant activities, nutrient homeostasis, and osmolyte accumulation.

Surface engineered mesoporous silica carriers for the controlled delivery of anticancer drug 5-fluorouracil: Computational approach for the drug-carrier interactions using density functional theory.

Introduction: Drug delivery systems are the topmost priority to increase drug safety and efficacy. In this study, hybrid porous silicates SBA-15 and its derivatives SBA@N and SBA@3N were synthesized and loaded with an anticancer drug, 5-fluorouracil. The drug release was studied in a simulated physiological environment. Method: These materials were characterized for their textural and physio-chemical properties by scanning electron microscopy (SEM), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), small-angle X-ray diffraction (SAX), and nitrogen adsorption/desorption techniques. The surface electrostatics of the materials was measured by zeta potential. Results: The drug loading efficiency of the prepared hybrid materials was about 10%. In vitro drug release profiles were obtained in simulated fluids. Slow drug release kinetics was observed for SBA@3N, which released 7.5% of the entrapped drug in simulated intestinal fluid (SIF, pH 7.2) and 33% in simulated body fluid (SBF, pH 7.2) for 72 h. The material SBA@N presented an initial burst release of 13% in simulated intestinal fluid and 32.6% in simulated gastric fluid (SGF, pH 1.2), while about 70% of the drug was released within the next 72 h. Density functional theory (DFT) calculations have also supported the slow drug release from the SBA@3N material. The release mechanism of the drug from the prepared carriers was studied by first-order, second-order, Korsmeyer-Peppas, Hixson-Crowell, and Higuchi kinetic models. The drug release from these carriers follows Fickian diffusion and zero-order kinetics in SGF and SBF, whereas first-order, non-Fickian diffusion, and case-II transport were observed in SIF. Discussion: Based on these findings, the proposed synthesized hybrid materials may be suggested as a potential drug delivery system for anti-cancer drugs such as 5-fluorouracil.

Chemically synthesised flavone and coumarin based isoxazole derivatives as broad spectrum inhibitors of serine ß-lactamases and metallo-ß-lactamases: a computational, biophysical and biochemical study.

The ß-lactam antibiotics are the most effective medicines for treating bacterial infections. Resistance to them, particularly through the production of ß-lactamases, which can hydrolyse all kinds of ß-lactams, poses a threat to their continued use. The synthesised flavone and coumarin based isoxazole derivatives have the potential to be used as broad-spectrum inhibitors of the mechanistically different serine-(SBL) and metallo-ß-lactamases (MBL). The synthesised compounds were discovered as potent ß-lactamase inhibitors using molecular docking and in silico pharmacokinetic analysis. We studied the binding of chemically synthesised inhibitors to clinically significant ß-lactamases of class A, B, and C using biophysical and biochemical approaches, and computational analyses. These molecules follow Lipinski's rule of five and have acceptable solubility, permeability, and oral bioavailability. These molecules were found to be non-toxic and non-carcinogenic. MIC results suggest that these molecules restore the antibiotic efficacy against class A, B, and C ß-lactamases. Kinetics data showed that these molecules reduce the catalytic efficiency of clinically relevant class A, B, and C ß-lactamases. Fluorescence study showed significant interaction between these flavone-/coumarin-based isoxazole derivatives and class A/B/ C ß-lactamases. This study showed promising effect of these new generation compounds as broad spectrum ß-lactamase inhibitors of both SBLs and MBLs.Communicated by Ramaswamy H. Sarma.

Preoperative and postoperative urinary NGAL levels in children with bladder exstrophy.

BACKGROUND: Urinary NGAL (neutrophil gelatinase-associated lipocalin) levels have been shown to predict renal damage in various medical conditions. The present study was conducted to study the role of urinary NGAL levels in children with bladder exstrophy-epispadias complex post single-stage total reconstruction (SSTR) as markers of early renal function reduction. METHODS: Urine samples were collected from children with bladder exstrophy before SSTR (Group A, n = 11), 5 years post SSTR (Group B, n = 40) and controls (Group C, n = 41) and stored at - 20 °C. NGAL levels were estimated using double antibody sandwich ELISA. RESULTS: Mean NGAL levels in Groups A, B and C were 1.39, 34.24 and 2.58 ng/ml, respectively. Mean NGAL levels among Group B subjects with glomerular filtration rate (GFR) ≥ 80 ml/min/1.73 m2 body surface area (BSA) was 29.8 ng/ml, while it was 31.74 ng/ml in those with GFR < 80 ml/min. Urine samples were also evaluated 6 months post SSTR. Mean NGAL at 6 months was 6.76 ng/ml, while at 12 months it was 30.3 ng/ml, remaining > 30 ng/ml at 18 and 24 months. Dimercaptosuccinic acid (DMSA) scans did not show any scarring, and GFR on diethylenetriamine pentaacetate (DTPA) scans remained stable. CONCLUSIONS: Increasing levels of urinary NGAL following bladder-exstrophy and epispadias complex repair suggest that NGAL detects the earliest signs of renal damage even before any deterioration is observed in DMSA and/or DTPA-GFR scans. Further studies with an adequate sample size and periodic measurement of NGAL need to be performed before any definitive conclusion can be drawn.

Potential Health Risks of Zn, Fe, and Pb in Medical Skin Creams and Cosmetic Products Derived from Plants in Iraq.

Medical skin creams (SC) and cosmetic products (CP) specially derived from plants have natural chemicals as ingredients which are a major source of heavy metal releases. Therefore, the presence of harmful heavy metals in these materials is a matter of concern. This study has been carried out to assess the concentrations of heavy metals such as zinc (Zn), iron (Fe), and lead (Pb) in skin creams and cosmetic products that are available in Iraqi pharmacies using atomic absorption spectroscopy. Thirty-three samples from different Iraqi pharmacies of beauty creams, including 13 samples of skin creams and ten samples of cosmetic products. Health risk parameters such as chronic daily intake (CDI), total non-cancer risk (H.I.), and total cumulative cancer risk (TCCR) have been calculated. Based on the results, it is found that the average value of Zn, Fe, and Pb concentrations for SC samples in unit mg/kg were 65.33 ± 14.56, 100.52 ± 21.05, and 2.62 ± 0.64, respectively. At the same time, the average value of Zn, Fe, and Pb concentrations for CP samples in unit mg/kg were 2.30 ± 0.48, 24.18 ± 6.87, and 4.79 ± 1.18, respectively. The results of health risk exposure for SC samples were higher than those for CP samples. But, the values of health risk parameters were within acceptable limits according to Environmental Protection Agency (EPA). Consequently, there is no potential health risk for using medical skin creams and cosmetic products in the present study by Iraqi people.