Spectrofluorometric determination of futibatinib in human plasma and pharmaceutical formulations.

Futibatinib is a powerful inhibitor of fibroblast growth factor receptors that impedes its phosphorylation and subsequently leading to a reduction in in cell viability across various cell lines. Futibatinib was approved for initial use as an effective treatment for several diseases, including non-small cell lung cancer and breast cancer. Herein, a novel selective fluorescence probe was created for futibatinib quantification in various matrices, including pharmaceutical formulation and human plasma. The technique primarily depends on futibatinib's chemical conversion into a fluorescent product through a reaction with trimethylamine and bromoacetyl bromide. The created fluorescent probe exhibits maximum emission peak at 338 nm upon excitation at 248 nm. The method provided a low detection limit of 0.120 ng/mL and maintained a linear concentration-dependent relationship across the range of 1-200 ng/mL. High sensitivity, accuracy and precision were demonstrated for futibatinib quantification in pharmaceutical formulation and spiked plasma matrix by the method, which was validated in accordance with ICH requirements.

Farnesol prevents chlorpyrifos nephrotoxicity by modulating inflammatory mediators, Nrf2 and FXR and attenuating oxidative stress.

Chlorpyrifos (CPF) is a broad-spectrum insecticide widely employed in agricultural field for pest control. Exposure to CPF is associated with serious effects to the main organs, including kidneys. Significant evidence denotes that oxidative stress (OS) and inflammation are implicated in CPF toxicity. This study aimed to evaluate the potential of farnesol (FAR) to modulate inflammatory mediators and farnesoid-X-receptor (FXR) and Nrf2 in a rat model of CPF nephrotoxicity. CPF and FAR were orally supplemented for 28 days and blood and kidney samples were collected for investigations. CPF administration elevated blood creatinine and urea, kidney MDA and NO, and upregulated NF-κB p65, IL-1ß, TNF-α, iNOS, and caspase-3. In addition, CPF upregulated kidney Keap1, and decreased GSH, antioxidant enzymes, and Nrf2, FXR, HO-1 and NQO-1. FAR ameliorated creatinine and urea, prevented histopathological alterations, decreased MDA and NO, and enhanced antioxidants in CPF-administered rats. FAR modulated NF-κB p65, iNOS, TNF-α, IL-1ß, caspase-3, Keap1, HO-1, NQO-1, Nrf2 and FXR. In silico investigations revealed the binding affinity of FAR towards Keap1 and FXR, as well as NF-κB, caspase-3, iNOS, and HO-1. In conclusion, FAR prevents CPF-induced kidney injury by attenuating OS, inflammation, and apoptosis, effects associated with modulation of FXR, Nrf2/HO-1 signaling and antioxidants.

Theoretical investigations on modeling blood flow through vessel for understanding effectiveness of magnetic nanocarrier drug delivery systems.

For cancer therapy, the focus is now on targeting the chemotherapy drugs to cancer cells without damaging other normal cells. The new materials based on bio-compatible magnetic carriers would be useful for targeted cancer therapy, however understanding their effectiveness should be done. This paper presents a comprehensive analysis of a dataset containing variables x(m), y(m), and U(m/s), where U represents velocity of blood through vessel containing ferrofluid. The effect of external magnetic field on the fluid flow is investigated using a hybrid modeling. The primary aim of this research endeavor was to construct precise and dependable predictive models for velocity, utilizing the provided input variables. Several base models, including K-nearest neighbors (KNN), decision tree (DT), and multilayer perceptron (MLP), were trained and evaluated. Additionally, an ensemble model called AdaBoost was implemented to further enhance the predictive performance. The hyper-parameter optimization technique, specifically the BAT optimization algorithm, was employed to fine-tune the models. The results obtained from the experiments demonstrated the effectiveness of the proposed approach. The combination of the AdaBoost algorithm and the decision tree model yielded a highly impressive score of 0.99783 in terms of R2, indicating a strong predictive performance. Additionally, the model exhibited a low error rate, as evidenced by the root mean square error (RMSE) of 5.2893 × 10-3. Similarly, the AdaBoost-KNN model exhibited a high score of 0.98524 using R2 metric, with an RMSE of 1.3291 × 10-2. Furthermore, the AdaBoost-MLP model obtained a satisfactory R2 score of 0.99603, accompanied by an RMSE of 7.1369 × 10-3.

Comparative impact of replacing fish meal with azolla on growth, water quality, and physiology of red tilapia fingerlings at varying salinities.

A 210-day experiment to assess the efficacy of substituting azolla plant powder at levels of 0, 20, 40, and 60% for fish meal on red tilapia fingerlings (RTF, initial weight of 18.23 ± 0.12 g) performance under salinity levels of 5, 18, and 28ppt. Among the various conditions, RTF-fed 20% azolla at 28 and 5ppt salinity showcased the highest specific growth rate (SGR), whereas the lowest SGR was observed in fish-fed 60% azolla at 5ppt salinity. Upon azolla incorporation, noteworthy elevations in phytoplankton, zooplankton, dissolved oxygen (DO), pH, NH3, and NO3 were noted and conversely, azolla introduction led to decreased NH4 and NO2 concentrations in all salinity levels. Further, a significant (p < 0.05) interaction between azolla levels and water salinity (S×A) significantly impacted the hematological parameters of RTF. The highest levels of superoxide dismutase (SOD), catalase (CAT), and total protein (TP) were found in RTF-fed 20% azolla at 28ppt salinity, while the lowest CAT and TP levels occurred in RTF-fed 60% azolla at 5ppt salinity. The highest aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were recorded in the RTF group fed 60% azolla at 5ppt salinity, with the lowest values seen in the group given 20% azolla at 28ppt salinity. RTF fed a 20% azolla diet at 18ppt salinity exhibited the highest lysozyme value, in contrast to the lowest value observed in the RTF group fed the control diet at 18ppt salinity. In conclusion, this study recommends the utilization of azolla at inclusion levels ranging from 20 to 40%, as it has the potential to notably enhance the immune system and elevate the survival rate of RTF.

Tailoring of Bilosomal Nanogel for Augmenting the Off-Label Use of Sildenafil Citrate in Pediatric Pulmonary Hypertension.

Pediatric pulmonary hypertension is a serious syndrome with significant morbidity and mortality. Sildenafil is widely used off-label in pediatric patients with pulmonary arterial hypertension. In this study, bile salt-stabilized nanovesicles (bilosomes) were screened for their efficacy to enhance the transdermal delivery of the phosphodiesterase type 5 inhibitor, sildenafil citrate, in an attempt to augment its therapeutic efficacy in pediatric pulmonary hypertension. A response surface methodology was implemented for fabricating and optimizing a bilosomal formulation of sildenafil (SDF-BS). The optimized SDF-BS formulation was characterized in terms of its entrapment efficiency (EE), zeta potential, vesicle size, and in vitro release profile. The optimized formula was then loaded onto hydroxypropyl methyl cellulose (HPMC) hydrogel and assessed for skin permeation, in vivo pharmacokinetics, and pharmacodynamic studies. The optimized SDF-BS showed the following characteristic features; EE of 88.7 ± 1.1%, vesicle size of 185.0 + 9.2 nm, zeta potential of -20.4 ± 1.1 mV, and efficiently sustained SDF release for 12 h. Skin permeation study revealed a remarkable improvement in SDF penetration from bilosomal gel compared to plain SDF gel. In addition, pharmacokinetic results revealed that encapsulating SDF within bilosomal vesicles significantly enhanced its systemic bioavailability (∼3 folds), compared to SDF oral suspension. In addition, pharmacodynamic investigation revealed that, compared to plain SDF gel or oral drug suspension, SDF-BS gel applied topically triggered a significant elevation (p < 0.05) in cGMP serum levels, underscoring the superior therapeutic efficacy of SDF-BS gel. Conclusively, bilosomes can be viewed as a promising nanocarrier for transdermal delivery of SDF that would grant higher therapeutic efficiency while alleviating the limitations encountered with SDF oral administration.

Correction: Optimal sizing and power losses reduction of photovoltaic systems using PSO and LCL filters.

[This corrects the article DOI: 10.1371/journal.pone.0301516.].

Cumin (Cuminum cyminum L.) seeds accelerates wound healing in rats: Possible molecular mechanisms.

Wound healing is a complex, intricate, and dynamic process that requires effective therapeutic management. The current study evaluates the wound healing potentials of methanolic extract of Cuminum cyminum L. seeds (CCS) in rats. Sprague Dawley (24) rats were distributed into four cages, wounds produced on the back of the neck, and received two daily topical treatments for 14 days: A, rats received normal saline; B, wounded rats treated with intrasite gel; C and D, rats received 0.2 mL of 250 and 500 mg/kg of CCS, respectively. After that, wound area and closure percentage were evaluated, and wound tissues were dissected for histopathological, immunohistochemical, and biochemical examinations. Acute toxicity trials of methanolic extract of CCS showed the absence of any physiological changes or mortality in rats. CCS application caused a significant reduction in wound size and a statistically elevated percentage of wound contraction than those of vehicle rats. CCS treatment caused significant up-regulation of collagen fiber, fibroblasts, and fewer inflammatory cells (inflammation) in granulation tissues. TGF-ß1 (angiogenetic factor) was significantly more expressed in CCS-treated rats in comparison to normal saline-treated rats; therefore, more fibroblasts transformed into myofibroblasts (angiogenesis). CCS-treated rats showed remarkable antioxidant potentials (higher SOD and CAT enzymes) and decreased MDA (lipid peroxidation) levels in their wound tissue homogenates. Hydroxyproline amino acid (collagen) was significantly up-regulated by CCS treatment, which is commonly related to faster wound closure area. The outcomes suggest CCS as a viable new source of pharmaceuticals for wound treatment.

CETARS/CAR Practice Guideline on Imaging the Pregnant Trauma Patient.

Imaging of pregnant patients who sustained trauma often causes fear and confusion among patients, their families, and health care professionals regarding the potential for detrimental effects from radiation exposure to the fetus. Unnecessary delays or potentially harmful avoidance of the justified imaging studies may result from this understandable anxiety. This guideline was developed by the Canadian Emergency, Trauma and Acute Care Radiology Society (CETARS) and the Canadian Association of Radiologists (CAR) Working Group on Imaging the Pregnant Trauma Patient, informed by a literature review as well as multidisciplinary expert panel opinions and discussions. The working group included academic subspecialty radiologists, a trauma team leader, an emergency physician, and an obstetriciangynaecologist/maternal fetal medicine specialist, who were brought together to provide updated, evidence-based recommendations for the imaging of pregnant trauma patients, including patient safety aspects (eg, radiation and contrast concerns) and counselling, initial imaging in maternal trauma, specific considerations for the use of fluoroscopy, angiography, and magnetic resonance imaging. The guideline strives to achieve clarity and prevent added anxiety in an already stressful situation of injury to a pregnant patient, who should not be imaged differently.

Evaluation of data representation techniques for vibration based road surface condition classification.

The accurate classification of road surface conditions plays a vital role in ensuring road safety and effective maintenance. Vibration-based techniques have shown promise in this domain, leveraging the unique vibration signatures generated by vehicles to identify different road conditions. In this study, we focus on utilizing vehicle-mounted vibration sensors to collect road surface vibrations and comparing various data representation techniques for classifying road surface conditions into four classes: normal road surface, potholes, bad road surface, and speedbumps. Our experimental results reveal that the combination of multiple data representation techniques results in higher performance, with an average accuracy of 93.4%. This suggests that the integration of deep neural networks and signal processing techniques can produce a high-level representation better suited for challenging multivariate time series classification issues.

Study of the Adsorption and Separation Behavior of Scandium and Zirconium by Trialkyl Phosphine Oxide-Modified Resins in Sulfuric and Hydrochloric Acid Media.

Zirconium is recognized as one of the main impurities of the rare earth element scandium during purification. It presents significant challenges due to its similar chemical properties, making separating it difficult. This study used trialkyl phosphine oxide (TRPO) as a functional ligand, and the effects of carrier type and acidity on adsorption performance were first investigated. Among these, the novel extraction resin SiO2-P as a carrier for TRPO demonstrated more prominent separation performance in 0.2 M H2SO4 and 5 M HCl solutions. The kinetic and isotherm data were consistent with the pseudo-secondary kinetics and Langmuir model, respectively, and the adsorption process could be regarded as homogeneous monolayer adsorption subject to the dual effects of chemisorption and internal diffusion. In addition, thermodynamic analysis showed that the adsorption process of zirconium under the experimental conditions was a spontaneous endothermic process. Combined with the results of SEM-EDS, FT-IR, and XPS analyses, scandium and zirconium were successfully adsorbed by the resin and uniformly distributed on its surface, and the greater affinity of the P=O groups on the resin for zirconium was the critical factor contributing to the separation of scandium and zirconium. Finally, scandium and zirconium in sulfuric acid and hydrochloric acid media were extracted and separated by column experiments, and the purity of scandium could reach 99.8% and 99.99%, respectively.

Semi-simultaneous hand-assisted laparoscopic (HAL) bilateral nephrectomy and kidney transplantation from the same incision in ADPKD, first case report in Saudi Arabia.

This case report discusses the management of a 46-year-old male patient with autosomal dominant polycystic kidney disease and a high body mass index, who underwent a semi-simultaneous procedure involving hand-assisted laparoscopic bilateral nephrectomy to alleviate severe abdominal symptoms and prepare for a kidney transplantation, all using the same incision. This is the first reported occurrence of such a procedure in Saudi Arabia. Post-operatively, the patient made a successful recovery with excellent kidney function and no complications.

Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia.

Bimatoprost (BIM) is a prostaglandin F2α analogs originally approved for the treatment of glaucoma and ocular hypertension. Recent studies have highlighted its potential to boost hair growth. The objective of this investigation is to challenge the potential of spanlastics (SLs) as a surfactant-based vesicular system for promoting the cutaneous delivery of BIM for the management of alopecia. BIM-loaded spanlastics (BIM-SLs), composed of Span as the main vesicle component and Tween as the edge activator, were fabricated by ethanol injection method. The formulated BIM-SLs were optimized by 23 full factorial design. The optimized formula (F1) was characterized for entrapment efficiency, surface charge, vesicle size, and drug release after 12 h (Q12h). The optimized formula (F1) exhibited high drug entrapment efficiency (83.1 ± 2.1%), appropriate zeta potential (-19.9 ± 2.1 mV), Q12h of 71.3 ± 5.3%, and a vesicle size of 364.2 ± 15.8 nm, which favored their cutaneous accumulation. In addition, ex-vivo skin deposition studies revealed that entrapping BIM within spanlastic-based nanogel (BIM-SLG) augmented the dermal deposition of BIM, compared to naïve BIM gel. Furthermore, in vivo studies verified the efficacy of spanlastic vesicles to boost the cutaneous accumulation of BIM compared to naive BIM gel; the AUC0-12h of BIM-SLG was 888.05 ± 72.31 µg/mL.h, which was twice as high as that of naïve BIM gel (AUC0-12h 382.86 ± 41.12 µg/mL.h). Intriguingly, BIM-SLG outperforms both naïve BIM gel and commercial minoxidil formulations in stimulating hair regrowth in an androgenetic alopecia mouse model. Collectively, spanlastic vesicles might be a potential platform for promoting the dermal delivery of BIM in managing alopecia.

Knowledge and attitude toward transcranial magnetic stimulation among rehabilitation specialists in Saudi Arabia.

Research has demonstrated the benefits of transcranial magnetic stimulation (TMS) in rehabilitation. TMS has been widely used in clinical and research settings for individuals with and without neurological dysfunctions. Therefore, understanding the knowledge and attitudes of rehabilitation specialists regarding TMS is crucial for its application. To our knowledge, no such studies have previously been conducted in the rehabilitation field. Therefore, this study is the first to assess rehabilitation specialists' knowledge of and attitudes toward TMS. An observational cross-sectional study using a self-administered online survey was conducted among 102 rehabilitation specialists to assess their knowledge and attitudes regarding TMS application in rehabilitation sciences. Descriptive and inferential statistics were used to describe the knowledge and attitudes of rehabilitation specialists toward TMS and examine the impact of different factors such as gender, education level, acceptability, and practice on these outcomes. Rehabilitation specialists who participated in this study showed a limited level of general knowledge of TMS in rehabilitation (7.81 ± 6.20, 37.19%). However, a significant association between educational levels and knowledge was found. Higher knowledge scores were observed for specialists with post-graduate degrees compared to those with only a bachelor's degree. Moreover, knowledge level, experience, and availability of TMS equipment in the workplace led to a positive attitude toward TMS among rehabilitation specialists. A low knowledge level among rehabilitation specialists was attributed to their level of education. Nevertheless, specialists showed an overall positive attitude toward TMS. Therefore, customized medical education is necessary to incorporate TMS theory and applications into neuroscience and rehabilitation courses for rehabilitation specialists as it holds significant promise as a therapeutic tool.

Development and Optimization of Proniosomal Formulation of Irbesartan Using a Box-Behnken Design to Enhance Oral Bioavailability: Physicochemical Characterization and In Vivo Assessment.

This research work aimed to develop and evaluate proniosomes for the oral delivery of the lipophilic drug Irbesartan (IRB) to improve its solubility and bioavailability. Proniosomes of Irbesartan were formulated using a lipid, surfactant, and carrier by a slurry method. Based on the prepared preliminary trial batches and their evaluation, the formulation was optimized by employing a Box-Behnken design (BBD) in which concentrations of span 60 (X1), cholesterol (X2), and mannitol (X3) were used as three independent variables and the vesicular size (VS) (Y1), % entrapment efficiency (% EE) (Y2), and % cumulative drug release (% CDR) (Y3) were used as dependent variables. The optimized batch B1 was obtained from the BBD experiment after validation of checkpoint analysis, and their characterization was done for VS, % EE, % CDR, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. The optimized batch showed a VS of 199 ± 5.4 nm, a % EE of 99.25 ± 2.24%, and a % CDR of 97.36 ± 1.13% at 24 h. Scanning electron microscopy (SEM) study showed a smooth surface of batch B1. DSC and XRD studies indicated the amorphous nature of the proniosomal formulation. The proniosomal formulation showed increased solubility (2.65 ± 0.2 mg/mL) in phosphate buffer, pH 6.8, as compared to water (0.059 ± 0.02 mg/mL). The pharmacokinetic study in rats confirmed the increased bioavailability of the drug in optimized proniosomal formulation compared with its pure drug suspension. Cmax, Tmax, and AUC0-t of the drug also increased by 2-fold compared to those of drug suspension. Thus, in conclusion, the proniosomal formulation proved to be an efficient carrier for improved oral delivery of Irbesartan by improving the solubility and bioavailability of the drug.

Design and synthesis of new quinazolinone derivatives: investigation of antimicrobial and biofilm inhibition effects.

New quinazolin-4-ones 9-32 were synthesized in an attempt to overcome the life-threatening antibiotic resistance phenomenon. The antimicrobial screening revealed that compounds 9, 15, 16, 18, 19, 20 and 29 are the most broad spectrum antimicrobial agents in this study with safe profile on human cell lines. Additionally, compounds 19 and 20 inhibited biofilm formation in Pseudomonas aeruginosa, which is regulated by quorum sensing system, at sub-minimum inhibitory concentrations (sub-MICs) with IC50 values 3.55 and 6.86 µM, respectively. By assessing other pseudomonal virulence factors suppression, it was found that compound 20 decreased cell surface hydrophobicity compromising bacterial cells adhesion, while both compounds 19 and 20 curtailed the exopolysaccharide production which constitutes the major component of the matrix binding biofilm components together. Also, at sub-MICs Pseudomonas cells twitching motility was impeded by compounds 19 and 20, a trait which augments the cells pathogenicity and invasion potential. Molecular docking study was performed to further evaluate the binding mode of candidates 19 and 20 as inhibitors of P. aeruginosa quorum sensing transcriptional regulator PqsR. The achieved results demonstrate that both compounds bear promising potential for discovering new anti-biofilm and quorum quenching agents against Pseudomonas aeruginosa without triggering resistance mechanisms as the normal bacterial life cycle is not disturbed.

Antibiotics efficacy in clinical and microbiological cure of uncomplicated urinary tract infection: a systematic review and network meta-analysis.

PURPOSE: Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. RESULTS: We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). CONCLUSION: The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.

Employing Piper longum extract for eco-friendly fabrication of PtPd alloy nanoclusters: advancing electrolytic performance of formic acid and methanol oxidation.

Advancement in bioinspired alloy nanomaterials has a crucial impact on fuel cell applications. Here, we report the synthesis of PtPd alloy nanoclusters via the hydrothermal method using Piper longum extract, representing a novel and environmentally friendly approach. Physicochemical characteristics of the synthesized nanoclusters were investigated using various instrumentation techniques, including X-ray photoelectron spectroscopy, X-ray diffraction, and High-Resolution Transmission electron microscopy. The electrocatalytic activity of the biogenic PtPd nanoclusters towards the oxidation of formic acid and methanol was evaluated chronoamperometry and cyclic voltammetry studies. The surface area of the electrocatalyst was determined to be 36.6 m2g-1 by Electrochemical Surface Area (ECSA) analysis. The biologically inspired PtPd alloy nanoclusters exhibited significantly higher electrocatalytic activity compared to commercial Pt/C, with specific current responses of 0.24 mA cm - 2 and 0.17 mA cm - 2 at synthesis temperatures of 180 °C and 200 °C, respectively, representing approximately four times higher oxidation current after 120 min. This innovative synthesis approach offers a promising pathway for the development of PtPd alloy nanoclusters with enhanced electrocatalytic activity, thereby advancing fuel cell technology towards a sustainable energy solution.

Evaluation of cytocompatibility and cell proliferation of electrospun chitosan/polyvinyl alcohol/montmorillonite clay scaffold with l929 cell lines in skin regeneration activity and in silico molecular docking studies.

The present investigation describes the development of a novel Chitosan/Polyvinyl Alcohol/Montmorillonite Clay (CS/PVA/MMT) scaffold by adopting an electrospinning method, and their biocompatibility was evaluated in vitro with L929 fibroblast cell line to ascertain its use in wound healing applications. The fabricated scaffold was characterized using analytical techniques. FT-IR measurement exhibited the existence of relevant functional groups and XRD implies scaffolds' amorphous nature. The scaffold's morphology and pore diameter were assessed using TEM and SEM. The pore diameter of the as-prepared scaffold was approximately 125 nm. The antimicrobial assay of the scaffold was evaluated against selected pathogens which demonstrated higher antimicrobial efficacy. The scavenging activity tested using the DPPH assay showed remarkable scavenging capability. The wound healing properties were tested through the Cytotoxicity assay conducted on the L929 assay which proved the scaffold to be a suitable material for cell proliferation. Also, a Molecular docking investigation was carried out for CS/PVA/MMT ligand using human neutrophil elastase (HNE) 1H1B protein as a receptor in the CB-Dock server. Studies conducted in silico revealed strong interaction and high binding energy ratings of CS/PVA/MMT ligand with key residues of human neutrophil elastase (HNE) 1H1B proteins that help in tissue regeneration activity.

Stevioside mitigates lead toxicity in thinlip mullet juveniles: Impacts on growth, metabolism, and immune function.

This study investigates the impact of varying concentrations of stevioside in the presence of lead (Pb) exposure on multiple aspects of thinlip mullet (Liza ramada) juveniles. Over 60 days, a total of 540 juvenile L. ramada with an initial weight of 3.5 ± 0.13 g were evenly distributed into six groups, each consisting of three replicates. The experimental diet consisted of varying levels of stevioside (150, 250, 350, and 450 mg/kg diet), with a consistent concentration of lead (Pb) set at 100 µg/kg diet. Stevioside demonstrated a positive influence on growth parameters, with the 450 mg/kg +Pb treatment showing the highest values. Biochemical parameters remained stable, but lead-exposed fish without stevioside displayed signs of potential liver damage and metabolic issues. Stevioside supplementation, especially at higher doses (≥250 mg/kg), reversed these negative effects, restoring biochemical markers to healthy control levels. Lead exposure significantly suppressed antioxidant enzyme activities, but co-administration of stevioside exhibited a dose-dependent protective effect, with 250, 350, and 450 mg/kg groups showing activities comparable to the healthy control. Lead-exposed fish without stevioside demonstrated attenuation of the immune response, but stevioside supplementation reversed these effects, particularly at ≥250 mg/kg. Stev (≥250 mg/kg) reduced IL-1ß and hepcidin expression, contrasting dose-dependent upregulation in lower dosages and lead-only group. Histological examinations of the intestine and liver supported these findings. In conclusion, stevioside, especially at 450 mg, positively impacted growth, biochemical parameters, antioxidant activity, immune response, and gene expression in L. ramada exposed to lead, suggesting its potential to mitigate lead toxicity in aquaculture. Additional research is warranted to investigate the long-term impacts of stevioside supplementation and its prospective implementation in aquaculture.