Dual effect of polyaromatic hydrocarbons on sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity of a teleost fish (Oncorhynchus mykiss).

Polycyclic aromatic hydrocarbons (PAHs) are embryo- and cardiotoxic to fish that might be associated with improper intracellular Ca2+ management. Since sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) is a major regulator of intracellular Ca2+, the SERCA activity and the contractile properties of rainbow trout (Oncorhynchus mykiss) ventricle were measured in the presence of 3- and 4-cyclic PAHs. In unfractionated ventricular homogenates, acute exposure of SERCA to 0.1-1.0 µM phenanthrene (Phe), retene (Ret), fluoranthene (Flu), or pyrene (Pyr) resulted in concentration-dependent increase in SERCA activity, except for the Flu exposure, with maximal effects of 49.7-83 % at 1 µM. However, PAH mixture did not affect the contractile parameters of trout ventricular strips. Similarly, all PAHs, except Ret, increased the myotomal SERCA activity, but with lower effect (27.8-40.8 % at 1 µM). To investigate the putative chronic effects of PAHs on SERCA, the atp2a2a gene encoding trout cardiac SERCA was expressed in human embryonic kidney (HEK) cells. Culture of HEK cells in the presence of 0.3-1.0 µM Phe, Ret, Flu, and Pyr for 4 days suppressed SERCA expression in a concentration-dependent manner, with maximal inhibition of 49 %, 65 %, 39 % (P < 0.05), and 18 % (P > 0.05), respectively at 1 µM. Current findings indicate divergent effects of submicromolar PAH concentrations on SERCA: stimulation of SERCA activity in acute exposure and inhibition of SERCA expression in chronic exposure. The depressed expression of SERCA is likely to contribute to the embryo- and cardiotoxicity of PAHs by depressing muscle function and altering gene expression.

Deep learning enhances acute lymphoblastic leukemia diagnosis and classification using bone marrow images.

Acute lymphoblastic leukemia (ALL) poses a significant health challenge, particularly in pediatric cases, requiring precise and rapid diagnostic approaches. This comprehensive review explores the transformative capacity of deep learning (DL) in enhancing ALL diagnosis and classification, focusing on bone marrow image analysis. Examining ten studies conducted between 2013 and 2023 across various countries, including India, China, KSA, and Mexico, the synthesis underscores the adaptability and proficiency of DL methodologies in detecting leukemia. Innovative DL models, notably Convolutional Neural Networks (CNNs) with Cat-Boosting, XG-Boosting, and Transfer Learning techniques, demonstrate notable approaches. Some models achieve outstanding accuracy, with one CNN reaching 100% in cancer cell classification. The incorporation of novel algorithms like Cat-Swarm Optimization and specialized CNN architectures contributes to superior classification accuracy. Performance metrics highlight these achievements, with models consistently outperforming traditional diagnostic methods. For instance, a CNN with Cat-Boosting attains 100% accuracy, while others hover around 99%, showcasing DL models' robustness in ALL diagnosis. Despite acknowledged challenges, such as the need for larger and more diverse datasets, these findings underscore DL's transformative potential in reshaping leukemia diagnostics. The high numerical accuracies accentuate a promising trajectory toward more efficient and accurate ALL diagnosis in clinical settings, prompting ongoing research to address challenges and refine DL models for optimal clinical integration.

Revolutionizing chronic lymphocytic leukemia diagnosis: A deep dive into the diverse applications of machine learning.

Chronic lymphocytic leukemia (CLL) is a B cell neoplasm characterized by the accumulation of aberrant monoclonal B lymphocytes. CLL is the predominant type of leukemia in Western countries, accounting for 25% of cases. Although many patients remain asymptomatic, a subset may exhibit typical lymphoma symptoms, acquired immunodeficiency disorders, or autoimmune complications. Diagnosis involves blood tests showing increased lymphocytes and further examination using peripheral blood smear and flow cytometry to confirm the disease. With the significant advancements in machine learning (ML) and artificial intelligence (AI) in recent years, numerous models and algorithms have been proposed to support the diagnosis and classification of CLL. In this review, we discuss the benefits and drawbacks of recent applications of ML algorithms in the diagnosis and evaluation of patients diagnosed with CLL.

Application of lime peel oil composite nanoemulsion to prevent toxigenic fungi in nuts.

Food byproduct oils may have antimicrobial impacts when used in coating and preservation. Nuts are known to suffer from toxigenic fungi and their related mycotoxins. The present study utilized lime oil emulsion to minimize fungal infection and reduce aflatoxin B1 (AFB1). Besides, it evaluated lime oil's impact on nuts' protection against oxidation and deterioration during storage. Lime oil was extracted using hydrodistillation, and gas chromatography (GC-MS) evaluated volatile constituents. Oil was loaded into a composite emulsion of whey protein, Arabic gum, gelatin, and carboxymethyl cellulose. The antimicrobial and antifungal properties of the nut-coating emulsion were evaluated. A simulated Aspergillus flavus infection experiment evaluated composite resistance for fungal infection and AFB1 production. Oxidation and acidity changes in nuts oil composition were evaluated by proximate analysis, fatty acid composition, and induction period. The oil majority was recorded for terpenes and monoterpenes, including limonene (44.69 ± 2.11%). The emulsion was characterized by zeta potential (-21.16 ± 1.28 mV), stability (99.61 ± 0.02%), and polydispersity index (0.41 ± 0.05). Antimicrobial properties recorded a high antibacterial inhibition zone (up to 28.37 ± 0.11 mm) and anti-mycotoxigenic fungi (up to 37.61 ± 0.24 mm). For the simulated experiment, fungal growth reduction ranged between 78.02% for filmed-peanut and 84.5% for filmed-almond, while AFB1 was not detected in filmed hazelnut and almond. During the one-year storage of samples, there was a slight change in nut oil composition and oxidation progress in filmed nuts, while there was a significant change in non-filmed nuts. The result recommended lime-composite as an edible nut coating that prevents aflatoxigenic contamination, oxidation changes, and improved shelf life.

Extraction and characterization of bioactive secondary metabolites from lactic acid bacteria and evaluating their antifungal and antiaflatoxigenic activity.

Aflatoxins are toxic carcinogens and mutagens formed by some moulds, specifically Aspergillus spp. Therefore, this study aimed to extract and identify bioactive secondary metabolites from Lactobacillus species, to evaluate their efficacy in reducing fungal growth and aflatoxin production and to investigate their toxicity. The bioactive secondary metabolites of Lactobacillus species showed variable degrees of antifungal activity, whereas L. rhamnosus ethyl acetate extract No. 5 exhibited the highest antifungal activity and, thus, was selected for further identification studies. Data revealed that L. rhamnosus ethyl acetate extract No. 5 produced various organic acids, volatile organic compounds and polyphenols, displayed antifungal activity against A. flavus, and triggered morphological changes in fungal conidiophores and conidiospores. L. rhamnosus ethyl acetate extract No. 5 at a 9 mg/mL concentration reduced AFB1 production by 99.98%. When the effect of L. rhamnosus ethyl acetate extract No. 5 on brine shrimp mortality was studied, the extract attained a 100% mortality at a concentration of 400 µg/mL, with an IC50 of 230 µg/mL. Meanwhile, a mouse bioassay was performed to assess the toxicity of L. rhamnosus ethyl acetate extract No. 5, whereas there were no harmful effects or symptoms in mice injected with L. rhamnosus ethyl acetate extract at concentrations of 1, 3, 5, 7, and 9 mg/kg body weight.

Integrating AI and ML in Myelodysplastic Syndrome Diagnosis: State-of-the-Art and Future Prospects.

Myelodysplastic syndrome (MDS) is composed of diverse hematological malignancies caused by dysfunctional stem cells, leading to abnormal hematopoiesis and cytopenia. Approximately 30% of MDS cases progress to acute myeloid leukemia (AML), a more aggressive disease. Early detection is crucial to intervene before MDS progresses to AML. The current diagnostic process for MDS involves analyzing peripheral blood smear (PBS), bone marrow sample (BMS), and flow cytometry (FC) data, along with clinical patient information, which is labor-intensive and time-consuming. Recent advancements in machine learning offer an opportunity for faster, automated, and accurate diagnosis of MDS. In this review, we aim to provide an overview of the current applications of AI in the diagnosis of MDS and highlight their advantages, disadvantages, and performance metrics.

One pot synthesis of two potent Ag(I) complexes with quinoxaline ligand, X-ray structure, Hirshfeld analysis, antimicrobial, and antitumor investigations.

In one pot, the self-assembly of AgNO3 and 2-chloroquinoxaline (2Cl-quinox) in water-ethanol mixture afforded two novel crystalline Ag(I) complexes. The major product is the polymeric complex [Ag(2Cl-quinox)(NO3)]n; (1), while the minor product (2) comprises two molecules which are the monomeric [Ag(2Cl-quinox)2(NO3)]; (2a) and polymeric [Ag(2Cl-quinox)(NO3)]n; (2b) complexes. The single crystal X-ray structure revealed that 1 and 2b are made up of two-dimensional infinite sheets. In contrast, 2a is a monomeric complex which has a highly distorted tetrahedral geometry around Ag(I) center. In all cases, the 2Cl-quinox molecule acts as a terminal monodentate ligand. Complexes 1 and 2b have similar molecular structures and also have almost similar crystal packing. Using Hirshfeld surface analysis, the O…H hydrogen bonds and π-π stacking interactions contributed significantly to the molecular packing. Both complexes have broad-spectrum action towards multi drug-resistance bacteria. The most effective function of 2 is against Proteus morganii, with a MIC value of 8 µg/mL. Complex 2 (IC50 = 5.93 ± 0.52 µg/mL) has remarkably greater cytotoxic effect against lung carcinoma (A-549) than cis-platin (IC50 = 7.5 ± 0.69 µg/mL) and AgNO3 (IC50 = 14.7 ± 0.53 µg/mL). The higher Ag-content in 2 could be the main reason for its higher cytotoxicity than 1.

Prevention of Aflatoxin Occurrence Using Nuts-Edible Coating of Ginger Oil Nanoemulsions and Investigate the Molecular Docking Strategy.

The modern utilization of essential oils such as ginger oil (GO) as an anti-aflatoxin represents a potential target for food preservation and safety; however, the mechanism of action is still unclear. Nanoemulsions, through an edible coating, can enhance the oil's bioactivity, increase its hydrophilicity, and extend the final product's shelf-life. In the present study, two edible films for the GO nanoemulsion were prepared by ultrasonication using carboxymethyl cellulose (FB1-GO) and sodium alginate (FB2-GO). The droplet size of FB2-GO was finer (126.54 nm) compared to FB1-GO (289.77 nm). Meanwhile, both had high stability proved by z-potential; +31.54 mV (FB1-GO) and +46.25 mV (FB2-GO) with low PDI values (<0.4). Using gas chromatography-mass spectrometry, the hydrodistilled GO showed 25 compounds, representing 99.17% of the total oil, with α-zingiberene (29.8%), geranial (10.87%), ß-bisabolene (8.19%), and ar-curcumene (5.96%) as the predominant. A dramatic increase in α-zingiberene, α-bisabolene and ar-curcumene was due to the homogenization conditions in both FB1-GO and FB2-GO compared to the GO. The FB1-GO exhibited superior antibacterial activity against the examined strains of bacterial pathogens, while FB2-GO was more effective as an antifungal agent on the tested Aspergillus fungi strains. In a simulated liquid media, FB2-GO inhibited the total growth of fungi by 84.87−92.51% and showed the highest reduction in the aflatoxin amount produced. The in silico study presented that, among the GO volatile constituents, sesquiterpenes had the highest binding free energies against the enzymes responsible for aflatoxin production compared to monoterpenes. α-Bisabolene showed the highest affinity toward polyketide synthase (−7.5 Kcal/mol), while ar-curcumene was the most potent against cytochrome P450 monooxygenase (−8.3 Kcal/mol). The above findings clarify the reasons for aflatoxin reduction in simulated media during incubation with FB1-GO and FB2-GO.

Green synthesis of novel stable biogenic gold nanoparticles for breast cancer therapeutics via the induction of extrinsic and intrinsic pathways.

Biosynthesis of gold nanoparticles (AuNPs) using algal polysaccharides is a simple, low-cost, and an eco-friendly approach. In the current study, different concentrations of Arthospira platensis exopolysaccharides (EPS) were used to synthetize AuNPs via the reduction of gold ions. The biologically synthesized AuNPs (AuNPs1, AuNPs2, AuNPs3) were prepared in 3 different forms through the utilization of three different ratios of EPS-reducing agents. AuNPs analysis confirmed the spherical shape of the EPS-coated AuNPs. Furthermore, AuNPs prepared by EPS and L-ascorbic acid (AuNPs3) showed more stability than the AuNPs colloidal solution that was prepared using only L-ascorbic acid. Analysis of the antimicrobial effects of AuNPs showed that E. coli was the most sensitive bacterial species for AuNPs3 and AuNPs1 with inhibition percentages of 88.92 and 83.13%, respectively. Also, safety assay results revealed that AuNPs3 was the safest biogenic AuNPs for the tested noncancerous cell line. The anticancer assays of the biogenic AuNPs1, AuNPs2, and AuNPs3 against MCF-7 cell line indicated that this cell line was the most sensitive cell line to all treatments and it showed inhibition percentages of 66.2%, 57.3%, and 70.2% to the three tested AuNPs, respectively. The AuNPs also showed abilities to arrest MCF-7 cells in the S phase (77.34%) and increased the cellular population in the sub G0 phase. Gene expression analysis showed that AuNPs3 down regulated Bcl2, Ikapα, and Survivn genes in MCF-7 treated-cells. Also, transmission electron microscopy (TEM) analysis of MCf-7 cells revealed that AuNPs 3 and AuNPs2 were localized in cell vacuoles, cytoplasm, and perinuclear region.

Duodenal transection following a seat belt injury: A case report.

INTRODUCTION AND IMPORTANCE: The rare presentation of duodenal injuries has led to a lack of guidelines for managing and diagnosing such cases. In most duodenal injuries, intramural hematoma and perforation are seen; however, complete resection of the duodenum is rare, which is seen in our case. CASE PRESENTATION: We report a rare case of a 6-year-old boy who suffered from a complete isolated duodenal transection at the pylorus and a 90% transection at D3 and D4 following a seat-belt injury. The surgeon performed a primary anastomosis for the first part of the duodenum with pyloric exclusion. Then, primary repair with controlled fistula for the second transection at D3 and D4 and a gastrojejunostomy were performed. After further management, the patient was discharged with no further complaints. CLINICAL DISCUSSION: Due to the retroperitoneal location of the duodenum, it is challenging to diagnose a duodenal injury. CT scan with contrast is considered the best diagnostic tool in the case of a duodenal injury. Treatment of duodenal injuries depends on the type of injury and the present level of damage. It is imperative to differentiate between a duodenal hematoma, a duodenal perforation, or a duodenal transection as the management for each complication differs. CONCLUSION: No official guidelines have been set in the case of management or diagnosis of duodenal transection. Based on our experience with this patient and similar literature, guidelines for managing and diagnosing duodenal transection should be set, and further studies on the matter are warranted.

Total phenolics, flavonoids, and antioxidant activity of agricultural wastes, and their ability to remove some pesticide residues.

Organophosphorus pesticides (OPPs) cause great risk to human health as they are used globally. Therefore, the purpose of this research was to determine the total phenolics, flavonoids, and antioxidant activity of agricultural waste, as well as to control the pesticide residues (diazinon, and parathion) at a laboratory scale level using dried-milled fruit wastes. The pesticide residues parathion and diazinon were used at concentrations of 0.094, and 1.90 mg/mL respectively. The fruit wastes used in this study were orange and banana peels, as well as date stones, and they were used in two concentrations (3 and 9 g/30 mL deionized water). The total phenolic and flavonoid contents and the antioxidant activity were measured in fruit wastes. Also, the Fourier transmitted infrared (FTIR) spectra of fruit wastes were established to figure out the nature of the functional groups found before and after pesticide residues removal. The ability of fruit wastes to remove pesticides residues was determined using Gas Chromatography/Mass spectrometry (GC/MS). Data showed that date stones contained a higher amount of total phenolic content than orange and banana peels. However, orange peels contained a higher amount of total flavonoid contents than those of date stones and banana peels. As for antioxidant activity, banana peels recorded the higher antioxidant activity, followed by orange peels and date stones respectively. Results revealed that there was no relation between total phenolic content, total flavonoid content, and antioxidant activity. Results also indicated that date stones at a concentration of 9 g successfully reduced diazinon (81.18%), followed by banana (63.86%) and orange peels (43.42%) respectively, whereas parathion was reduced by banana peels at a concentration of 9 g (50.34%), followed by orange peels (45.28%), and date stones (39.52%) respectively. This study demonstrated that agricultural wastes were effective in the adsorption of diazinon from water, and their use is considered safe for the environment.

Spent Coffee Grounds Valorization as Bioactive Phenolic Source Acquired Antifungal, Anti-Mycotoxigenic, and Anti-Cytotoxic Activities.

Spent coffee grounds (SCGs), which constitute 75% of original coffee beans, represent an integral part of sustainability. Contamination by toxigenic fungi and their mycotoxins is a hazard that threatens food production. This investigation aimed to examine SCGs extract as antimycotic and anti-ochratoxigenic material. The SCGs were extracted in an eco-friendly way using isopropanol. Bioactive molecules of the extract were determined using the UPLC apparatus. The cytotoxicity on liver cancer cells (Hep-G2) showed moderate activity with selectivity compared with human healthy oral epithelial (OEC) cell lines but still lower than the positive control (Cisplatin). The antibacterial properties were examined against pathogenic strains, and the antifungal was examined against toxigenic fungi using two diffusion assays. Extract potency was investigated by two simulated models, a liquid medium and a food model. The results of the extract showed 15 phenolic acids and 8 flavonoids. Rosmarinic and syringic acids were the most abundant phenolic acids, while apigenin-7-glucoside, naringin, epicatechin, and catechin were the predominant flavonoids in the SCGs extract. The results reflected the degradation efficiency of the extract against the growth of Aspergillus strains. The SCGs recorded detoxification in liquid media for aflatoxins (AFs) and ochratoxin A (OCA). The incubation time of the extract within dough spiked with OCA was affected up to 2 h, where cooking was not affected. Therefore, SCGs in food products could be applied to reduce the mycotoxin contamination of raw materials to the acceptable regulated limits.

Synthesis, X-ray Structure, Hirshfeld, DFT and Biological Studies on a Quinazolinone-Nitrate Complex.

The reaction of 4-hydroxyquinazoline (4HQZ) with aqueous solution of nitric acid afforded the corresponding quinazolinone-nitrate (4HQZN) complex in very good yield. The crystal structure of 4HQZN was determined and its structural and supramolecular structural aspects were analyzed. 4HQZN crystallized in the space group P21/c and monoclinic crystal system with one [4HQZ-H]+[NO3]- formula and Z = 4. Its supramolecular structure could be described as a 2D infinite layers in which the 4HQZN molecules are connected via N-H…O and C-H…O hydrogen bridges. Using DFT calculations, the relative stability of five suggested isomers of 4HQZN were predicted. It was found that the medium effects have strong impact not only on the isomers' stability but also on the structure of the 4HQZN. It was found that the structure of 4HQZN in DMSO and methanol matched well with the reported X-ray structure which shed the light on the importance of the intermolecular interactions on the isomers' stability. The structure of 4HQZN could be described as a proton transfer complex in which the nitrate anion acting as an e-donor whiles the protonated 4HQZ is an e-acceptor. In contrast, the structure of the isolated 4HQZN in gas phase and in cyclohexane could be described as a 4HQZ…HNO3 hydrogen bonded complex. Biological screening of the antioxidant, anticancer and antimicrobial activities of 4HQZ and 4HQZN was presented and compared. It was found that, 4HQZN has higher antioxidant activity (IC50 = 36.59 ± 1.23 µg/mL) than 4HQZ. Both of 4HQZ and 4HQZN showed cell growth inhibition against breast (MCF-7) and lung (A-549) carcinoma cell lines with different extents. The 4HQZ has better activity with IC50 of 178.08 ± 6.24 µg/mL and 119.84 ± 4.98 µg/mL, respectively. The corresponding values for 4HQZN are 249.87 ± 9.71 µg/mL and 237.02 ± 8.64 µg/mL, respectively. Also, the antibacterial and antifungal activities of 4HQZN are higher than 4HQZ against all studied microbes. The most promising result is for 4HQZN against A. fumigatus (MIC = 312.5 µg/mL).

Characterization of Orange Peel Extract and Its Potential Protective Effect against Aluminum Chloride-Induced Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Hence, developing an effective treatment or protective agent is crucial for public health. The present study aims to characterize orange peel extract (OPE) through in vitro and in silico studies. Furthermore, it examines the protective effect of OPE against experimentally-induced Alzheimer's disease in rats. The total phenolic and flavonoid content of OPE was 255.86 ± 1.77 and 52.06 ± 1.74 (mg/100 g), respectively. Gallic acid, the common polyphenol in OPE detected by HPLC was 3388.60 µg/100 g. OPE antioxidant IC50 was 67.90 ± 1.05, 60.48 ± 0.91, and 63.70 ± 0.30 by DPPH, ABTS and Hydroxyl radical scavenging activity methods, respectively. In vitro anti-acetylcholinesterase (AChE) IC50 was 0.87 ± 0.025 mg/mL for OPE and 2.45 ± 0.001 mg/mL for gallic acid. Molecular docking analysis for human AChE (4EY7) with donepezil, gallic acid, and acetylcholine showed binding energy ΔG values of -9.47, -3.72, and -5.69 Kcal/mol, respectively. Aluminum chloride injection (70 mg/Kg/day for 6 weeks) induced Alzheimer's-like disease in male rats. OPE (100 and 200 mg/kg/d) and gallic acid (50 mg/kg/d) were administered orally to experimental animals for 6 weeks in addition to aluminum chloride injection (as protective). OPE was found to protect against aluminum chloride-induced neuronal damage by decreasing both gene expression and activity of acetylcholinesterase (AChE) and a decrease in amyloid beta (Aß42) protein level, thiobarbituric acid-reactive substances (TBARS), and nitric oxide (NO), and increased reduced glutathione (GSH) level and activity of the antioxidant enzymes in the brain tissues. Additionally, gene expressions for amyloid precursor protein (APP) and beta secretase enzyme (BACE1) were downregulated, whereas those for presinilin-2 (PSEN2) and beta cell lymphoma-2 (BCL2) were upregulated. Furthermore, the reverse of mitochondrial alternation and restored brain ultrastructure might underlie neuronal dysfunction in AD. In conclusion, our exploration of the neuroprotective effect of OPE in vivo reveals that OPE may be helpful in ameliorating brain oxidative stress, hence protecting from Alzheimer's disease progression.

Validation of New ELISA Technique for Detection of Aflatoxin B1 Contamination in Food Products versus HPLC and VICAM.

Toxin-contaminated foods and beverages are a major source of illness, may cause death, and have a significant negative economic impact worldwide. Aflatoxin B1 (AFB1) is a potent toxin that may induce cancer after chronic low-level exposure. This study developed a quantitative recombinant AflR gene antiserum ELISA technique for aflatoxin B1 detection in contaminated food products. Aflatoxin B1 residuals from 36 food samples were analyzed with HPLC and VICAM. DNA was extracted from aflatoxin-contaminated samples and the AflR gene amplified using PCR. PCR products were purified and ligated into the pGEM-T vector. Recombinant plasmids were sequenced and transformed into competent E. coli (BL21). Molecular size and B-cell epitope prediction for the recombinant protein were assessed. The purified protein was used to induce the production of IgG antibodies in rabbits. Serum IgG was purified and labeled with alkaline phosphatase. Finally, indirect-ELISA was used to test the effectiveness of polyclonal antibodies for detection of aflatoxin B1 in food samples.

Cardiac Toxicity of Cadmium Involves Complex Interactions Among Multiple Ion Currents in Rainbow Trout (Oncorhynchus mykiss) Ventricular Myocytes.

Cadmium (Cd2+ ) is cardiotoxic to fish, but its effect on the electrical excitability of cardiac myocytes is largely unknown. To this end, we used the whole-cell patch-clamp method to investigate the effects of Cd2+ on ventricular action potentials (APs) and major ion currents in rainbow trout (Oncorhynchus mykiss) ventricular myocytes. Trout were acclimated to +4 °C, and APs were measured at the acclimated temperature and elevated temperature (+18 °C). Cd2+ (10, 20, and 100 µM) altered the shape of the ventricular AP in a complex manner. The early plateau fell to less positive membrane voltages, and the total duration of AP prolonged. These effects were obvious at both +4 °C and +18 °C. The depression of the early plateau is due to the strong Cd2+ -induced inhibition of the L-type calcium (Ca2+ ) current (ICaL ), whereas the prolongation of the AP is an indirect consequence of the ICaL inhibition: at low voltages of the early plateau, the delayed rectifier potassium (K+ ) current (IKr ) remains small, delaying repolarization of AP. Cd2+ reduced the density and slowed the kinetics of the Na+ current (INa ) but left the inward rectifier K+ current (IK1 ) intact. These altered cellular and molecular functions can explain several Cd2+ -induced changes in impulse conduction of the fish heart, for example, slowed propagation of the AP in atrial and ventricular myocardia (inhibition of INa ), delayed relaxation of the ventricle (prolongation of ventricular AP duration), bradycardia, and atrioventricular block (inhibition of ICaL ). These findings indicate that the cardiotoxicity of Cd2+ in fish involves multiple ion currents that are directly and indirectly altered by Cd2+ . Through these mechanisms, Cd2+ may trigger cardiac arrhythmias and impair myocardial contraction. Elevated temperature (+18 °C) slightly increases Cd2+ toxicity in trout ventricular myocytes. Environ Toxicol Chem 2021;40:2874-2885. © 2021 SETAC.

Satisfaction Survey of Women After Cosmetic Genital Procedures: A Cross-Sectional Study From Saudi Arabia.

BACKGROUND: Female cosmetic genital surgery (FCGS) aims for better aesthetic genital appearance and improved functional aspects to enhance women's self-esteem and satisfaction. OBJECTIVES: This study aims to assess the satisfaction of women who have undergone FCGS and its impact on their sexual, psychological, and aesthetic aspects. METHODS: An observational cross-sectional study was conducted in private clinics in Riyadh, Kingdom of Saudi Arabia, between March and June 2019, in women who underwent FCGS. Phone interviews were conducted in the Arabic language. The survey comprised 4 sections: demographics, motives for FCGS, quality-of-life questionnaires about genital appearance satisfaction, and sexual function. RESULTS: Out of the 196 women undergoing FCGS during the study period, 11.7% refused to participate, and 37.2% did not answer phone calls; 51% of the women participated in the study. The women's age ranged between 23 and 55 years; 64% underwent vaginoplasty, and 73% underwent other cosmetic procedures. Ninety-two percent of the women did not have any complications after these procedures. CONCLUSIONS: In this group of women, FCGS was safe and effective, and the majority of participants reported overall satisfaction and improvement of sexual function, genital appearance, and self-esteem.

Bioactive Components of Pomegranate Oil and Their Influence on Mycotoxin Secretion.

Pomegranate, similar to other fruits, has juice-extraction by-products. Pomegranate seed oil (PGO) is a non-traditional oil with health benefits, rich in bioactive components. This study was aimed to assess PGO phytochemicals and their influence as bioactive components to reduce mycotoxin secretion. The encapsulation was applied in micro and nanoforms to protect the quality and enhance the efficacy of the oil. The PGO was extracted using ultrasound-assisted methods. Carotenoids, tocochromanols, sterols, phenolic, flavonoid, antioxidant, and antimicrobial activity were determined. The fatty acid profile was analyzed by the GC-MS, while mycotoxin was determined utilizing the HPLC apparatus. The toxicity and protective action of oil were examined using the hepatocytes' cell line. The resultant oil acts as oleoresin that is rich in bioactive molecules. Phenolics and antioxidant potency recorded higher values compared to traditional vegetable oils, whereas polyunsaturated fatty acids were 87.51%. The major fatty acid was conjugated punicic acid (81.29%), which has high biological effects. Application of the PGO on fungal media reduced aflatoxins secretion up to 63%, and zearalenone up to 78.5%. These results confirm the bio-functionality of oil to regulate the fungal secondary metabolites process. The PGO is a unique prospective non-traditional oil and has several functionalities in food, which achieve nutritional, antioxidant, and anti-mycotoxigenic activities.

MicroRNA signature in patients with hepatocellular carcinoma associated with type 2 diabetes.

BACKGROUND: Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus (T2DM) and reported to be a risk factor for developing hepatocellular carcinoma (HCC). A reliable screening biomarker of liver cirrhosis (LC) and HCC among T2DM patients is important to reduce the morbidity and mortality of this disease. MicroRNA (miRNA) is considered a key player in HCC and T2DM, and it might be a hidden culprit in diabetes-associated HCC, making it a promising reliable prognostic tool. AIM: To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic patients. METHODS: Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing; then, RT-qPCR was used to validate significantly altered miRNAs between the two groups. Candidate miRNAs were tested in serum samples of 200 T2DM patients, 270 LC patients, 200 HCC patients, and 225 healthy control subjects. Additionally, receiver operating characteristic (ROC) analysis, with area under the curve (AUC), was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients (LC + T2DM). RESULTS: Expression of the sequenced miRNAs in serum was different in HCC vs LC-positive T2DM patients. Two miRNAs (miR-34a, miR-221) were significantly up-regulated and five miRNAs (miR-16, miR-23-3p, miR-122-5p, miR-198, miR-199a-3p) were significantly down-regulated in HCC compared to LC patients. Analysis of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients, as it could identify HCC with high diagnostic accuracy in diabetic LC patients (AUC = 0.993) and in diabetic nonmalignant patients (AUC = 0.961). CONCLUSION: This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic patients. The study recommends further research to shed light on a possible role of c-Met in T2DM-associated HCC via the miRNA regulatory pathway.

Protective efficacy using Cape- golden berry against pre-carcinogenic aflatoxins induced in rats.

Aflatoxins are harmful compounds that induced carcinogenic impacts on tissues. It could generate oxidative stress causing cells damage. Bioactive substances from natural plants could avoid mycotoxins' bad impacts. Cape-goldenberry (CGB), a source of active substances, was vacuum-dried at 30 °C then milled. Fresh and dried CGB-powder properties were estimated. Animal experiment was designed using six rat-groups to evaluate CBG effect to reduce harmful effect of aflatoxins. Rats treated groups were orally administrated by aflatoxins (AFs) with or without CGB in diets. Blood parameters, liver and kidney functions, serum lipids, and liver histological changes were estimated. The CGB powder showed several time doubles of phenolics, flavonoids, and antioxidants than fresh fruits. Diet supplementation by CGB of AFs-treated rats showed enhancement in final weight, food efficiency, and weight gain compared to AFs treatment only. Also, liver and kidney functions, liver enzymes, iron level, tumors indicator, and serum lipids of AFs- rats. Moreover, total protein, albumin, and globulin reduction by AFs have been improved by CGB presence in diets. Histopathological studies for AFs-rats liver showed dilated blood sinusoids with aggregation of inflammatory, Kupffer cell hyperplasia, degenerated hepatocytes, and apoptotic cells. However, in AFs-rat groups fed CGB in diets, liver hepatocytes appeared to be almost normal similar to the control. Results pointed out that CGB recorded a corrective action for aflatoxin B1 and G1 toxicity. This was recorded for the blood and serum parameters, and liver enzymes. This CGB action avoiding AFs-toxicity was more clearly declared in the liver tissues.