A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II.

Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber's rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

Case item creation and video case presentation as summative assessment tools for distance learning in the pandemic era.

BACKGROUND: There is an urgent need for more diverse methods for student evaluation, given the sudden shift to online learning necessitated by the coronavirus disease 2019 (COVID-19) pandemic. Innovative assessment tools will need to cover the required competencies and should be used to drive self-learning. Self-assessments and peer assessments may be added to the traditional classroom-based evaluations to identify individual insecurities or overconfidence. Identification of these factors is essential to medical education and is a focus of current research. METHODS: A modified operational assessment was introduced for the evaluation of third-year medical students. This intervention has facilitated sustained education and has promoted interactive student learning. Members of the entering class of 2017 participated in an integrated team and a competency-based online project that involved innovative item creation and case presentation methods. RESULTS: The new assessment process has been implemented successfully with positive feedback from all the participants; a usable product has been generated. CONCLUSIONS: We created new assessment tools in response to the COVID-19 pandemic that have been used successfully at our institution. These tools have provided a framework for integrated and interactive evaluations that can be used to facilitate the modification of traditional assessment methods.

Serum ACE2 and S19P gene polymorphism in Egyptian patients with COVID-19 infection: correlation with disease severity.

The expression of ACE2 is linked to disease severity in COVID-19 patients. The ACE2 receptor gene polymorphisms are considered determinants for SARS-CoV-2 infection and its outcome. In our study, serum ACE2 and its genetic variant S19P rs73635825 polymorphism were investigated in 114 SARS-CoV-2 patients. The results were compared with 120 control subjects. ELISA technique and allele discrimination assay were used for measuring serum ACE2 and genotype analysis of ACE2 rs73635825. Our results revealed that serum ACE2 was significantly lower in SARS-CoV-2 patients (p = 0.0001), particularly in cases with hypertension or diabetes mellitus. There was a significant difference in the genotype distributions of ACE2 rs73635825 A > G between COVID-19 patients and controls (p-value = 0.001). A higher frequency of the heterozygous AG genotype (65.8%) was reported in COVID-19 patients. The G allele was significantly more common in COVID-19 patients (p < 0.0001). The AG and GG genotypes were associated with COVID-19 severity as they were correlated with abnormal laboratory findings, GGO, CXR, and total severity scores with p < 0.05. Our results revealed that the ACE2 S19P gene variant is correlated with the incidence of infection and its severity, suggesting the usefulness of this work in identifying the susceptible population groups for better disease control.

Impact of dark septate endophytes on salt stress alleviation of tomato plants.

Fungal endophytes can improve plant tolerance to abiotic stress conditions. Dark septate endophytes (DSEs) belong to phylogenetically non-related groups of root colonizing fungi among the Ascomycota with high melanin-producing activities. They can be isolated from roots of more than 600 plant species in diverse ecosystems. Still the knowledge about their interaction with host plants and their contribution to stress alleviation is limited. The current work aimed to test the abilities of three DSEs (Periconia macrospinosa, Cadophora sp., Leptodontidium sp.) to alleviate moderate and high salt stress in tomato plants. By including an albino mutant, the role of melanin for the interaction with plants and salt stress alleviation could also be tested. P. macrospinosa and Cadophora sp. improved shoot and root growth 6 weeks after inoculation under moderate and high salt stress conditions. No matter how much salt stress was applied, macroelement (P, N, and C) contents were unaffected by DSE inoculation. The four tested DSE strains successfully colonized the roots of tomato, but the colonization level was clearly reduced in the albino mutant of Leptodontidium sp. Any difference in the effects on plant growth between the Leptodontidium sp. wild type strain and the albino mutant could, however, not be observed. These results show that particular DSEs are able to increase salt tolerance as they promote plant growth specifically under stress condition. Increased plant biomasses combined with stable nutrient contents resulted in higher P uptake in shoots of inoculated plants at moderate and high salt conditions and higher N uptake in the absence of salt stress in all inoculated plants, in P. macrospinosa-inoculated plants at moderate salt condition and in all inoculated plants except the albino mutants at high salt condition. In summary, melanin in DSEs seems to be important for the colonization process, but does not influence growth, nutrient uptake or salt tolerance of plants.

Use of mobile learning applications as an innovative method for the teaching of biochemistry.

BACKGROUND: Traditional teaching methods of biochemistry provide effective tools for knowledge transmission, but are considered less engaging with students. Smartphone applications may provide suitable alternatives to compensate for the shortcomings of traditional teaching methods. PURPOSE: This study aimed to assess the effectiveness of smartphone applications as a complementary method for learning biochemistry. METHODOLOGY: A total of 32 students, from the College of Applied Medical Sciences, University of Bisha, Saudi Arabia, were recruited. Students used available mobile applications, and their performance was monitored through assignments, presentations, practical evaluations, and pre- and post-tests. A self-administered structured questionnaire was used to survey the students' perceptions. It was validated by students enrolled at the College of Applied Medical Science, interns, and medical educators. It was checked for item appropriateness and comprehensiveness using face and content validity. RESULTS: Around 75% of the students found the mobile applications useful in learning biochemistry, 50% believed that they were easy to use and 100% believed that the breadth of the knowledge presented by these applications was comprehensive. The pedagogical effect of the use of mobile applications in learning biochemistry showed statistically significant differences in student performances post-use and pre-use of mobile applications with P values of 0.000, 0.028, 0.023, and 0.000 for tests, assignments, practical evaluation, and presentations, respectively. CONCLUSION: Students have a positive perception of the use of mobile applications, as it has significantly improved their academic performance in biochemistry.

Formulation and evaluation of Piroxicam nanosponge for improved internal solubility and analgesic activity.

Cyclodextrin nanosponges are solid nanoparticles, designed by cross-linking of cyclodextrin polymer; it has been used widely as a good delivery system for water insoluble drugs. The aim of this study is to enhance the solubility of Piroxicam (PXM) using ß-Cyclodextrin based nanosponges formulations. PXM nanosponge (PXM-NS) formulations were prepared using ß-cyclodextrin and carbonyldiimidazole as a cross linker, three ratios of ß-cyclodextrin to crosslinker in addition to three drug to nanosponges ratios were tested. Piroxicam nanosponge formulations were characterized for its particle size, zeta potential, physical compatibility and in vitro release. Stability studies at three temperatures (4 °C, 25 °C and 40 °C) were done for optimal formula. Finally, the in vivo analgesic activity and pharmacokinetic parameters of the optimal formula were conducted. The optimized PXM-NS formula (PXM-NS10) showed particle size (362 ± 14.06 nm), polydispersity index (0.0518), zeta potential (17 ± 1.05 mV), and %EE (79.13 ± 4.33). The dissolution study showed a significant increase in the amount of PXM dissolved compared with the unformulated drug. Stability studies confirmed that nanosponge showed accepted stability for 90 days at 4 °C and 25 °C. In vivo analgesic studies verified that there was a significant enhancement in the analgesic response to PXM in mice, and 1.42 fold enhancement in the relative bioavailability of PXM-NS10 as compared to commercial tablets. Nanosponge prepared under optimal conditions is an encouraging formula for increasing the solubility and therefore the bioavailability of Piroxicam.

Nano-Emulsion Based Gel for Topical Delivery of an Anti-Inflammatory Drug: In vitro and in vivo Evaluation.

Introduction: Arthritic disorder is a common disease in elderly patients and the most common cause of joint dysfunction. This study aims to design Piroxicam-loaded nanoemulsion (PXM-NE) formulations to enhance the analgesic and anti-inflammatory activity of the drug for topical use. Methods: The nanoemulsion preparations were designed based on a high-pressure homogenization technique and were characterized for particle size (PS), poly dispersity index (Pi), zeta potential (ZP), drug content, and the selected formula was investigated for its topical analgesic activity and pharmacokinetic parameters. Results: The characterizations showed that the PS was 310.20±19.84 nm, Pi was 0.15±0.02, and ZP was -15.74±1.6 mV for the selected formula. A morphology study showed that the PXM-NE droplets were spherical with a uniform size distribution. The in vitro release study showed a biphasic release pattern with a rapid release within the first 2 hours followed by a sustained release pattern. The analgesic activity for optimal formula was 1.66 times higher than the commercial gel with a double duration of analgesic activity. The Cmax was 45.73±9.95 and 28.48±6.44 ng/mL for the gel form of the selected formula and the commercial gel respectively. The relevant bioavailability of the selected formula was 2.41 higher than the commercial gel. Conclusion: The results showed good physicochemical properties, higher bioavailability, and a longer analgesic effect of PXM from nanoemulsion gel, as compared to the commercial product.

LncRNA HULC and miR-122 Expression Pattern in HCC-Related HCV Egyptian Patients.

Hepatocellular carcinoma (HCC) is a highly prevalent malignancy. It is a common type of cancer in Egypt due to chronic virus C infection (HCV). Currently, the frequently used lab test is serum α-fetoprotein. However, its diagnostic value is challenging due to its low sensitivity and specificity. Genetic biomarkers have recently provided new insights for cancer diagnostics. Herein, we quantified Lnc HULC and miR-122 gene expression to test their potential in diagnosis. Both biomarkers were tested in the sera of 60 HCC patients and 60 with chronic HCV using real-time RT-PCR. miR-122 was highly expressed in HCV patients with a significant difference from the HCC group (p = 0.004), which points towards its role in prognosis value as a predictor of HCC in patients with chronic HCV. HULC was more highly expressed in HCC patients than in the HCV group (p = 0.018), indicating its potential use in screening and the early diagnosis of HCC. The receiver operating characteristic (ROC) curve analysis showed their reliable sensitivity and specificity. Our results reveal that miR-122 can act as a prognostic tool for patients with chronic HCV. Furthermore, it is an early predictor of HCC. LncRNA HULC can be used as an early diagnostic tool for HCC.

Improving Sesame (Sesamum indicum L.) Seed Yield through Selection under Infection of Fusarium oxysporum f. sp. sesami.

Sesame (Sesamum indicum L.), the Queen of oilseeds, is infected with different pathogens, restricting its yield. Fusarium oxysporum f. sp. sesami is the most destructive disease of sesame worldwide, causing economic losses. This work aimed to develop new high-yielding strains, resistant and/or tolerant to Fusarium. Two cycles of pedigree selection were achieved under infection of Fusarium oxysporum f. sp. sesami. Two populations in the F2 (600 plants each) were used. The selection criteria were five single traits and another three restricted by yield. The restricted selection was better in preserving variability than the single trait selection. The observed genetic gain in percentage from the mid-parent in the F4-generation was significant for the eight selection criteria. Single trait selection proved to be an effective method for improving the selection criterion, but it caused deleterious effects on the other correlated traits in most cases. The seed yield increased by 30.67% and 20.31% from the better parent in the first and second populations, respectively. The infection% was significantly reduced by 24.04% in the first, and 9.3% in the second, population. The selection index improved seed yield, and its attributes can be recommended.

Synthesized nano particles of glimepiride via spray freezing into cryogenic liquid: characterization, antidiabetic activity, and bioavailability.

The aim of this work was to formulate glimepiride (class II drug) which is characterized by low solubility and high permeability as nanostructured particles using a cryogenic technique with an aid of water-soluble polymer to improve its aqueous solubility and hence its bioavailability. 27 formula of glimepiride nano size particles were prepared by a spray freezing into cryogenic liquid (SCFL) using poly vinyl pyrrolidone K-30 (PVP K-30); that three drug polymer ratio (1:1, 1:2, and 1:3), with three different volumes of feeding solution (50, 100, 150 mL), at three flow rates (10, 20, and 30 mL/min). The prepared formulations were evaluated for production yield, particle size, zeta potential, drug content, release rate, in vivo hypoglycemic activity, and bioavailability. All prepared formulations showed high production yield and drug content ranged between 91.1 ± 3.4% and 94.3 ± 1.8% and 95.1 ± 2.8% and 97.1 ± 2.5%, respectively. The mean particles size was ranged between 280 ± 62 nm and 520 ± 30 nm. The results of in vitro release study revealed significant enhancement in the solubility of prepared formulations compared with the pure drug. It was found that optimal formula showed a significant reduction in blood glucose levels in diabetic rats, and 1.79-fold enhancements in oral bioavailability compared with market tablets. Nanoparticle prepared by SCFL method is an encouraging formula for improving the solubility and the bioavailability of glimepiride.

Design and optimization of ganciclovir solid dispersion for improving its bioavailability.

Development of new approaches for oral delivery of an existing antiviral drug aimed to enhance its permeability and hence bioavailability. Ganciclovir (GC) is an antiviral drug that belongs to class III in biopharmaceutical classification. The encapsulation of poorly absorbed drugs within nanosized particles offers several characteristics to drug due to their acquired surface properties. In the following study, the solvent evaporation technique was used to incorporate GC, within elegant nanosize particles using cyclodextrin and shellac polymers for enhancing its permeability and release pattern. Formulation variables were optimized using 23 full factorial design. The prepared formulations were assessed for yield, particle size, content, and micromeritics behavior. The optimized formula (F6) was identified through differential scanning calorimetry and Fourier transform infrared. In vitro release and stability were also assessed. Pharmacokinetic parameters of optimized nano GC solid dispersion particles (NGCSD-F6) were finally evaluated. The optimized formula (F6) showed a mean particle size of 288.5 ± 20.7 nm, a zeta potential of about 23.87 ± 2.27, and drug content 95.77 ± 2.1%. The in vitro drug release pattern of F6 showed an initial burst release followed by a sustained release over the next 12 h. The optimized formula showed accepted stability upon storage at room and refrigerator temperatures for 6 months with good flowing properties (Carr's index = 18.28 ± 0.44). In vivo pharmacokinetic study in rabbits revealed 2.2 fold increases in the bioavailability of GC compared with commercial convention tablets. The study affords evidence for the success of the solid dispersion technique under specified conditions in improvement of bioavailability of GC.

Development, in vitro Evaluation, and in vivo Study of Adhesive Buccal Films for the Treatment of Diabetic Pediatrics via Trans Mucosal Delivery of Gliclazide.

Objective: Development and evaluation of bucco-adhesive films of Gliclazide for pediatric use. Methods: Sixteen films were formulated using a different combination of Gelatin, Hydroxy propyl methyl cellulose (HPMC), polyvinyl alcohol, Hydroxy propyl cellulose (HPC), chitosan, polyethylene glycol, sodium alginate, and carbopol. Compatibility study for drug and polymers was conducted using differential scanning calorimetry method and Fourier transform infrared spectroscopy. All films were examined for drug content, weight variation, thickness, swelling index, muco-adhesion and folding endurance. In vitro drug release has been completed for two hours. Stability studies were conducted at 4°C, 25°C, and 40°C for selected films. The optimized formulation based on in vitro data was selected for a bioavailability study in rabbits. Results: The selected film formula (carbopol 2%, HPMC 2%) did not demonstrate interactions between the drug and polymers, while it showed accepted content, muco-adhesion, and mechanical properties. The in vitro release study showed rapid and complete release of drug from films. Stability studies confirmed accepted stability of the selected film at 4°C and 25°C, but the film get hard with few particles at 40°C. The bioavailability studies conducted showed that there was 2.1 fold increase in the AUC0-24 of selected film compared with oral tablets. Conclusion: Bucco adhesive films of Gliclazide is a promising dosage form for the treatment of diabetes in children.

Nephroprotective Effect of Costus (Saussurea costus) Ethanolic Extract on Oxaliplatin®-induced Nephrotoxicity in Adult Male Wistar Rats.

<b>Background and Objective:</b> Oxaliplatin^® is an antineoplastic platinum-based compound; nephrotoxicity is one of its most serious side effects. This study aimed to explore the nephroprotective potential of Costus Ethanolic Extract (CEE) against Oxaliplatin^®-induced nephrotoxicity. <b>Materials and Methods:</b> Adult male Wistar rats, weighting 140-160 g, were randomly divided into four groups: (1) Normal rats, (2) Rats ingested with CEE (67.08 mg kg¹ day¹), (3) Rats injected (ip) with Oxaliplatin^® (10 mg kg¹ week¹) and (4) rats treated with CEE in combination Oxaliplatin^® injection. <b>Results:</b> After six weeks of treatments, the results revealed that CEE ingestion along with Oxaliplatin^® injection markedly minimized the Oxaliplatin^®-induced renal deterioration; this was evidenced by the significant reduction in serum urea, creatinine, uric acid, Tumor Necrosis Factor Alpha (TNF-α), Interleukin 1Beta (IL¹ß) and Sodium ion (Na⁺) levels as well as kidney Malondialdehyde (MDA), Nitric Oxide (NO) and DNA fragmentation values. Controversially, a marked rise in serum Calcium, Potassium Ion (K⁺) and Cluster of Differentiation 4 (CD4) levels besides renal Glutathione (GSH), Catalase (CAT) and Superoxide Dismutase (SOD) values. Similarly, the histopathological findings confirmed the biochemical ones as the CEE restored the Oxaliplatin^®-induced histological degenerations. <b>Conclusion:</b> In conclusion, CEE exhibited nephron-protection efficiency against Oxaliplatin^®-induced nephrotoxicity; this promising effect may be achieved through the antioxidant and radical scavenging activities of its constituents.

Vitamin D receptor (VDR) gene polymorphism in Egyptian vitiligo patients.

BACKGROUND: Vitiligo is an autoimmune dermatological disorder, precipitated by genetic and nongenetic factors leading to destruction of epidermal melanocytes. In Egypt, it has a prevalence rate of 1.2%. Vitamin D has stimulatory and protective effects on melanocytes and acts through its nuclear vitamin D receptor (VDR) on target cells. The consequences of polymorphisms in VDR have been previously studied for mapping their link with various disorders of autoimmune etiology. AIM OF THIS WORK: To study Apa-I and Taq-I VDR single-nucleotide polymorphisms (SNPs) and the risk to develop vitiligo. METHODS: Extracted genomic DNA from the venous blood of 60 patients and controls was amplified and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for analysis of VDR gene polymorphisms. Serum 25-hydroxyvitamin D3 (25-OH-D3) level was measured using ELISA technique. RESULTS: The most common VDR genotypes were AA and TT among both groups with no significant difference. Analysis of the frequency of combinations of genotypes revealed AATT as the most common among patients (36.7%) while in the control group, AATt is the most common (33.3%) but no significant difference was noted on comparison of both groups. The genotype allele tt appeared to be more expressed in patients with marginal significance value (P 0.053). Serum 25-OH-D3 showed a relatively decreased level among patients and controls with no statistically significant difference. CONCLUSION: Although VDR SNPs are not correlated with vitiligo, the elevated frequency of tt genotype among vitiligo patients may suggest the risk to develop the disease.

Nanoparticles of Lovastatin: Design, Optimization and in vivo Evaluation.

INTRODUCTION: The aim of the study was to optimize the processing factors of precipitation-ultrasonication technique to prepare nano-sized particles of Lovastatin (LA) for enhancing its solubility, dissolution rate and in vivo bioavailability. METHODS: LA nanoparticles (LANs) were prepared using precipitation-ultrasonication technique under different processing factors. LANs were characterized in terms of particle size, zeta potential and in vitro release. Stability studies at 4°C, 25°C and 40°C were conducted for optimum formulation. In addition, the in vivo bioavailability of the optimum formula was studied in comparison to a marketed product in white master rats. RESULTS: The optimized LAN formula (LAN15) had particle size (190±15), polydispersity index (0.626±0.11) and a zeta potential (-25±1.9 mV). The dissolution study of the nanosuspensions showed significant enhancement compared with pure drug. After 50 min, only 20.12±1.85% of LA was dissolved while 99.1±1.09% of LA was released from LAN15. Stability studies verified that nanosuspensions at 4°C and 25°C showed higher stability with no particle growth compared to the samples studied at 40°C. In vivo studies conducted in rats verified that there was 1.45-fold enhancement of Cmax of LAN15 as compared to marketed tablets. CONCLUSION: Nanoparticle prepared by ultrasonication-assisted precipitation method is a promising formula for enhancing the solubility and hence the bioavailability of Lovastatin.

Salt Stress Tolerance of Dark Septate Endophytes Is Independent of Melanin Accumulation.

Dark septate endophytes (DSEs) represent a diverse group of root-endophytic fungi that have been isolated from plant roots in many different natural and anthropogenic ecosystems. Melanin is widespread in eukaryotic organisms and possesses various functions such as protecting human skin from UV radiation, affecting the virulence of pathogens, and playing a role in development and physiology of insects. Melanin is a distinctive feature of the cell walls of DSEs and has been thought to protect these fungi from abiotic stress. Melanin in DSEs is assumed to be synthesized via the 1,8-dihydroxynaphthalene (DHN) pathway. Its function in alleviation of salt stress is not yet known. The aims of this study were: (i) investigating the growth responses of three DSEs (Periconia macrospinosa, Cadophora sp., and Leptodontidium sp.) to salt stress, (ii) analyzing melanin production under salt stress and, (iii) testing the role of melanin in salt stress tolerance of DSEs. The study shows that the three DSE species can tolerate high salt concentrations. Melanin content increased in the hyphae of all DSEs at 100 mM salt, but decreased at 500 mM. This was not reflected in the RNA accumulation of the gene encoding scytalone dehydratase which is involved in melanin biosynthesis. The application of tricyclazole, a DHN-melanin biosynthesis inhibitor, did not affect either salt stress tolerance or the accumulation of sodium in the hyphae. In addition, melanin biosynthesis mutants of Leptodontidium sp. did not show decreased growth performance compared to the wild-type, especially not at high salt concentrations. This indicates that DSEs can live under salt stress and withstand these conditions regardless of melanin accumulation.

Mini-Tablets versus Nanoparticles for Controlling the Release of Amoxicillin: In vitro/In vivo Study.

INTRODUCTION: Controlling the drug release from the dosage form at a definite rate is the main challenge for a successful oral controlled-release drug delivery system. In this study, mini-tablets (MTs) and lipid/polymer nanoparticles (LPNs) of lipid polymer and chitosan in different ratios were designed to encapsulate and control the release time of Amoxicillin (AMX). METHODS: Physical characteristics and in vitro release profiles of both MT and LPN formulations were studied. Antimicrobial activity and oral pharmacokinetics of the optimum MT and LPN formulations in comparison to market tablet were studied in rats. RESULTS: All designed formulations of AMX as MTs and LPNs showed accepted characteristics. MT-6 (Compritol/Chitosan 1:1) showed the greatest retardation among all prepared minitablet preparations, releasing about 79.5% of AMX over 8 h. In contrast, LPN-11 (AMX: Cr 1:3/Chitosan 1 mg/mL) had the slowest drug release, revealing the sustained release of 80.9% within 8 h. The MIC of both optimized tablet formula (MT-6) and LPNs formula (LPN-11) was around two-fold lower than the control against H. pylori. The Cmax of MT-6 and LPN11 were non significantly different compared with the marketed AMX product. While the bioavailability experiment proved that the relative bioavailability of the AMX was 1.85 and 1.8 after the oral use of LPN11 and MT-6, respectively, compared to the market tablet. CONCLUSION: The results verified that both controlled-release mini-tablets and lipid/polymer nanoparticles can be used for sustaining the release and hence improve the bioavailability of amoxicillin.

Unravelling the Role of Melanin in Cd and Zn Tolerance and Accumulation of Three Dark Septate Endophytic Species.

Dark septate endophytes (DSEs) are often trace element (TE)-tolerant fungi and are abundant in TE-polluted environments. The production of melanin, a black polymer found in cell walls, was hypothesized by several authors to play a role in the TE tolerance of DSEs. To test this hypothesis, we established a series of experiments using albino strains and melanin inhibitors and examined the responses to Cd and Zn. Six DSEs belonging to genera Cadophora sp., Leptodontidium sp. and Phialophora mustea, were evaluated. The strains mainly produced 1,8-dihydroxynaphthalene (DHN) melanin whereas 3,4-dihydroxyphenylalanin melanin was also synthetized. Cd and Zn decreased melanin synthesis in most of the strains. A reduction in melanin concentration in hyphae through the use of tricyclazole, an inhibitor of DHN-melanin synthesis, did not reduce the tolerance of the strains to Cd and Zn. Similarly, albino mutants of Leptodontidium sp. were not more sensitive to Cd and Zn than the WT strain. Moreover, tricyclazole-treated colonies accumulated less Cd but more Zn compared to untreated colonies. The Cd and Zn contents of Leptodontidium albino strains were variable and similar to that of the WT. The results suggest that melanin production is not an important functional trait that contributes to Cd and Zn tolerance, but might contribute to Cd accumulation.

Ferulic acid influences Nrf2 activation to restore testicular tissue from cadmium-induced oxidative challenge, inflammation, and apoptosis in rats.

Here, we examined the protective effect of ferulic acid (FA) on cadmium chloride (CdCl2 )-mediated reproductive toxicity in male rats. Animals were divided into four groups: control, FA (20 mg/kg), CdCl2 (6.5 mg/kg), and FA + CdCl2 . CdCl2 treatment evoked a significant increase in testis cadmium concentration in addition to obvious increase in testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Moreover, CdCl2 -induced oxidative damage through exhausting the cellular defenses (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione) and downregulating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression accompanied by increases of malondialdehyde and nitric oxide contents. Testicular inflammation was evident indicated by increased levels of interleukin-1ß and tumor necrosis factor-α in CdCl2 -treated rats. CdCl2 exposure also decreased the expression of the proliferating cell nuclear antigen and augmented apoptotic events associated with prominent histopathological alterations. However, FA coadministration mitigated the impaired hormonal level, apoptotic and inflammatory injuries elicited by CdCl2, and maintained the oxidant/antioxidant balance in testicular tissue via Nrf2 activation. PRACTICAL APPLICATIONS: Cadmium is an environmental toxicant and known to cause adverse effects including reproductive toxicity. However, antioxidant application has been found to protect against heavy metals-mediated toxic effects. Here, we examined the potential protective efficacy of ferulic acid against cadmium-mediated testicular impairments through estimating the amount of cadmium in the testis, hormonal profile, oxidative status, inflammatory response, apoptotic and proliferating markers in addition to the histopathological alterations. The obtained findings revealed that ferulic acid supplementation was able to abolish the testicular damages coupled with cadmium exposure. The protective efficiency of ferulic acid may correlated with its strong antioxidant, anti-inflammatory, and antiapoptotic activities; suggesting that ferulic acid may be used to ameliorate cadmium-induced testicular deficits.