Experimental Study to Investigate the Performance-Related Properties of Modified Asphalt Concrete Using Nanomaterials Al2O3, SiO2, and TiO2.

The dual nature of asphalt binder necessitates improvements to mitigate rutting and fatigue since it performs as an elastic material under the regime of rapid loading or cold temperatures and as a viscous fluid at elevated temperatures. The present investigation assesses the effectiveness of Nano Alumina (NA), Nano Silica (NS), and Nano Titanium Dioxide (NT) at weight percentages of 0, 2, 4, 6, and 8% in asphalt cement to enhance both asphalt binder and mixture performance. Binder evaluations include tests for consistency, thermal susceptibility, aging, and workability, while mixture assessments focus on Marshall properties, moisture susceptibility, resilient modulus, permanent deformation, and fatigue characteristics. NS notably improves binder viscosity by about 138% and reduces penetration by approximately 40.8% at 8% nanomaterial (NM) content, significantly boosting hardness and consistency. NS also enhances Marshall stability and decreases air voids, increasing the mix's durability. For moisture resistance, NS at 8% NM content elevates the Tensile Strength Ratio (TSR) to 91.0%, substantially surpassing the 80% standard. Similarly, NA and NT also show improved TSR values at 8% NM content, with 88.0% and 84.1%, respectively. Additionally, NS, NA, and NT reduce permanent deformation by 82%, 69%, and 64% at 10,000 cycles at 8% NM content, illustrating their effectiveness in mitigating pavement distress. Notably, while higher NM content generally results in better performance across most tests, the optimal NM content for fatigue resistance is 4% for NS and 6% for both NA and NT, reflecting their peak performance against various types of pavement distresses. These results highlight the significant advantages of nanoparticles in improving asphalt's mechanical properties, workability, stability, and durability. The study recommends further field validation to confirm these laboratory findings and ensure that enhancements translate into tangible improvements in real-world pavement performance and longevity.

Combination diuretic therapies in heart failure: Insights from GUIDE-IT.

Introduction: Diuretics are the mainstay of maintaining and restoring euvolemia in the management of heart failure. Loop diuretics are often preferred, however, combination diuretic therapy (CDT) with a thiazide diuretic is often used to overcome diuretic resistance and increase diuretic effect. We performed an analysis of the GUIDE-IT study to assess all-cause mortality and time to first hospitalizations in patients necessitating CDT. Methods: Patients from the GUIDE-IT dataset were stratified by their requirement for CDT with a thiazide to achieve euvolemia. A total of 894 patients were analyzed, 733 of which were treated with loop diuretics alone vs 161 used either chlorothiazide or metolazone in addition to loop diuretics. Kaplan-Meir curves were derived with log-rank p-values to evaluate for differences between the groups. Results: There was no significant difference in all-cause mortality regardless of CDT utilization status (mean survival of 612.704 days vs 603.326 days, p = 0.083). On subgroup analysis, there was no significant difference in all-cause mortality amongst those using loop diuretics compared to CDT in the BNP-guided therapy group, (mean survival time 576.385 days vs 620.585 days, p = 0.0523), nor the control group (614.1 days vs 588.9 days; p = 0.5728). Time to first hospitalization was reduced in all using CDT compared to loop diuretics alone (280.5 days vs 407.2 days, p < 0.0001). On subgroup analysis, both the BNP-guided group as well as the control group had reduced time to first hospitalization in the CDT group compared to those who did not require CDT (BNP group: 287.503 days vs 402.475 days, p ≤0.0001; control group 248.698 days vs 399.035 days, p = 0.0009). Conclusion: Use of CDT is associated with earlier time to hospitalization, though no association was identified with increased all-cause mortality. Further prospective studies are likely needed to determine the true risk and benefits of combination diuretic therapy.

Natural recovery of cardiac allograft diastolic function, a retrospective longitudinal report.

Cardiac allografts suffer diastolic dysfunction early post-heart transplantation (HTx) due to ischemic injury, however the natural course of diastology recovery post HTx remains unknown (Tallaj et al., 2007 [1]). We retrospectively reviewed 60 adult HTx patients between 2015 and 2021 at a single site. Invasive hemodynamics and echocardiograms were obtained at 2 weeks and 1, 3, 6, and 12 months post-HTx. RA strain by 2D feature tracking was compared to intracardiac pressure measurements. In all patients, we observed normalization of RV and RA filling pressures by post-operative week 12 and recovery of diastolic dysfunction by month 6. There was an inverse correlation between RV end-diastolic pressure and RA contractile (r = -0.192, p < 0.05) and reservoir (r = -0.128, p < 0.05) functions in the allograft. As the post-transplant care paradigm shifts away from invasive procedures, right atrial indices should be included in imaging-based allograft surveillance studies.

Tailoring meat products for the elderly: A comprehensive review.

The population of the elderly is projected to grow significantly in most of the developed countries in the near future. This should earn this demographic the title of 'Consumer of the future'. Meat has high quality proteins and essential vitamins which are important for all demographics but more so for the elderly due to their susceptibility to sarcopenia. This review explored the landscape of meat research and product development that meets the distinctive requirements of the elderly, drawing from published refereed articles, industry reports, and unpublished grey literature. The review emphasised the importance of understanding the evolving dietary and sensory requirements associated with ageing and how they intersect with meat consumption. One notable aspect observed is the diversity within the elderly population, which underscores the necessity for tailored approaches in meat product development to cater to the varying preferences and nutritional needs of different individuals. This review also highlights the ongoing efforts in developing meat-based products that span a spectrum of consistencies, ranging from solid to liquid forms, to accommodate the diverse needs of elderly consumers. Despite these advancements, the review found a discrepancy between the pace of meat product development for the elderly and the rapid advancements in kitchen-level technologies and suggests that further research is needed to bridge this gap and align product innovation with emerging technological trends.

Anti-dandruff effects of butterfly pea flowers (Clitoria ternatea)-based shampoo: A pretest-posttest control study.

Butterfly pea flower (Clitoria ternatea) may serve as an alternative anti-dandruff treatment; however, its effects on Malassezia spp. remain unexplored. The aim of this study was to explore the effects of C. ternatea as an herbal-based anti-dandruff treatment on Malassezia spp. DNA expression, plakoglobin levels, IL-8 levels, sebum levels, dandruff severity scores, adverse effects, and patient satisfaction. An experimental study with a pretest-posttest control design was conducted at the Outpatient Clinic of Dermatology and Venereology, Arifin Achmad Hospital, Pekanbaru, Indonesia, from November 2023 to January 2024. The flower of C. ternatea was used to formulate the shampoo. The study involved 70 female patients aged 18-25 with dandruff, who were divided into two groups: (a) experimental group using 20% C. ternatea shampoo and (b) control group using 2% ketoconazole shampoo. The present study found that 2% ketoconazole shampoo significantly reduced Malassezia spp. DNA expression compared to 20% C. ternatea shampooo (Clitoria ternatea: ΔCq=1.76±3.18; ketoconazole: ΔCq=3.77±2.90; p=0.008). No significant difference was observed in plakoglobin levels (C. ternatea: ΔCq=1.98±3.63; ketoconazole: ΔCq=2.50±2.36; p=0.427) or IL-8 levels (C. ternatea: ΔCq=3.46±4.00; ketoconazole: ΔCq=4.16 ± 3.62; p=0.459). C. ternatea significantly reduced sebum levels more than ketoconazole (C. ternatea: 1.16±0.98%; ketoconazole: 0.22±0.38%; p<0.001). Dandruff scores and patient satisfaction were similar for both shampoos (p=0.115 and p=0.336, respectively). Adverse effects were more common in the 2% ketoconazole shampoo group, affecting 21.2% of the patients. In conclusion, 2% ketoconazole shampoo is more effective in reducing Malassezia spp. DNA expression, while 20% C. ternatea shampoo offers better sebum control. Both shampoos are similarly effective in ameliorating dandruff severity and are well-tolerated, with fewer adverse effects reported for C. ternatea.

Multiscale mapping of transcriptomic signatures for cardiotoxic drugs.

Drug-induced gene expression profiles can identify potential mechanisms of toxicity. We focus on obtaining signatures for cardiotoxicity of FDA-approved tyrosine kinase inhibitors (TKIs) in human induced-pluripotent-stem-cell-derived cardiomyocytes, using bulk transcriptomic profiles. We use singular value decomposition to identify drug-selective patterns across cell lines obtained from multiple healthy human subjects. Cellular pathways affected by cardiotoxic TKIs include energy metabolism, contractile, and extracellular matrix dynamics. Projecting these pathways to published single cell expression profiles indicates that TKI responses can be evoked in both cardiomyocytes and fibroblasts. Integration of transcriptomic outlier analysis with whole genomic sequencing of our six cell lines enables us to correctly reidentify a genomic variant causally linked to anthracycline-induced cardiotoxicity and predict genomic variants potentially associated with TKI-induced cardiotoxicity. We conclude that mRNA expression profiles when integrated with publicly available genomic, pathway, and single cell transcriptomic datasets, provide multiscale signatures for cardiotoxicity that could be used for drug development and patient stratification.

Changes in Thyroglobulin Antibody Levels in Differentiated Thyroid Cancer Patients After Thyroidectomy: A Retrospective Study in Basrah, Iraq.

INTRODUCTION: Differentiated thyroid cancer (DTC), the most common endocrine malignancy is subdivided into papillary (the most common) and follicular type. Generally, DTC has a good prognosis with standard treatments such as surgery and, in some cases, radioactive iodine (RAI). Post-treatment follow-up includes thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) measurement and imaging to assess treatment success and detect recurrence. However, TgAb can interfere with Tg measurements, making it essential to measure TgAb at different times (months).  Aim of the study: The aim of this study was to evaluate the changes in TgAb level in DTC patients after thyroidectomy and its association with recurrence. METHODS: This was a retrospective cohort study done at the Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC), Basrah, Iraq, for individuals diagnosed with DTC between 2008 and 2023. The data collected were analyzed using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States). The categories were classified according to the TgAb level as: (i) elevated (>115 IU/ml) and (ii) normal (<115 IU/ml), where TgAb levels measured at 0-6 months, 6-12 months, 24-36 months, 36-48 months, and beyond 48 months. RESULTS: The mean age at diagnosis of the study population (n=108) was 40.15 years with a female-to-male ratio of 4:1. Among these individuals, 52.8% (n=57) were found to be obese. Total thyroidectomy was performed on 84.3% (n=91). Papillary thyroid cancer was diagnosed in 69.5% (n=75). TgAb levels were influenced by body mass index (BMI); higher BMI (>30kg/m2) was associated with less consistent TgAb normalization, particularly beyond 48 months (P = 0.04). The study found no significant differences in TgAb normalization based on gender, age, BMI, type of surgery, type of cancer, American Thyroid Association (ATA) risk of recurrence, or radioactive iodine (RAI) treatment. CONCLUSION:  Factors including gender, age, type of surgery, type of cancer, ATA risk of recurrence, and RAI treatment did not significantly affect TgAb normalization in DTC individuals over the study period. However, higher BMI is associated with less consistent TgAb normalization in the long term.

Newly synthesized chitosan nanoparticles loaded with caffeine/moringa leaf extracts Halt Her2, BRCA1, and BRCA2 expressions.

Breast cancer is among the highest morbidity and mortality rates in women around the world. In the present investigation we aimed to synthesis novel nanosystem combining two naturally important anticancer agents with different mechanism of action namely Moringa oleifera and caffeine. Firstly, chemical analysis of Moringa oleifera extract and caffeine was done by gas chromatography-mass spectroscopy (GC-MS) in order to assess the main chemical compounds present and correlate between them and the possible anticancer effect. The novel nanosystem was characterized through dynamic light scattering techniques which revealed the stability and homogeneity of the prepared M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles, while FTIR and transmission electron microscope (TEM) proved the shape and the successful incorporation of M. oleifera leaves extract/Caffeine onto the nanochitosan carrier. Our initial step was to assess the anticancer effect in vitro in cancer cell line MCF-7 which proved the significant enhanced effect of M. oleifera leaves extract/Caffeine nanosystem compared to M. oleifera leaves extract or caffeine loaded nanoparticles. Further studies were conducted in vivo namely tumor biomarkers, tumor volume, bioluminescence imaging, molecular and histopathological investigations. The present study proved the potent anticancer effect of the synthesized M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles. Mo/Caf/CsNPs exhibited a large number of apoptotic cells within the tumor mass while the adipose tissue regeneration was higher compared to the positive control. The prepared nanoparticles downregulated the expression of Her2, BRCA1 and BRCA2 while mTOR expression was upregulated. The aforementioned data demonstrated the successful synergistic impact of Moringa and caffeine in decreasing the carcinoma grade.

Anti-proliferation evaluation of new derivatives of indole-6-carboxylate ester as receptor tyrosine kinase inhibitors.

Aim: The main goal was to create two new groups of indole derivatives, hydrazine-1-carbothioamide (4a and 4b) and oxadiazole (5, and 6a-e) that target EGFR (4a, 4b, 5) or VEGFR-2 (6a-e). Materials & methods: The new derivatives were characterized using various spectroscopic techniques. Docking studies were used to investigate the binding patterns to EGFR/VEGFR-2, and the anti-proliferative properties were tested in vitro. Results: Compounds 4a (targeting EGFR) and 6c (targeting VEGFR-2) were the most effective cytotoxic agents, arresting cancer cells in the G2/M phase and inducing the extrinsic apoptosis pathway. Conclusion: The results of this study show that compounds 4a and 6c are promising cytotoxic compounds that inhibit the tyrosine kinase activity of EGFR and VEGFR-2, respectively.

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Left ventricular assist device implantation outcomes in patients with subcutaneous implantable cardioverter-defibrillators: A case series.

Background: Left ventricular assist devices (LVADs) may induce electromagnetic interference (EMI) affecting implanted cardiac devices, including more novel subcutaneous implantable cardiac defibrillators (S-ICDs). Methods: In this case series, the authors retrospectively reviewed courses of 6 patients with S-ICDs who underwent LVAD implantation at a single center. Results: Of the 6 patients reviewed, 4 experienced inappropriate ICD shocks, of which 3 resulted from EMI. Five of the 6 patients ultimately had S-ICD therapies disabled. Conclusions: Due to EMI resulting in inappropriate shocks and improved tolerability of malignant arrhythmias, deactivation or removal of S-ICDs should be considered in patients undergoing LVAD implantation.

The Role of Screening, Risk Factors, and Early Intervention in Preventing Diabetes in the Obese Population: A Systematic Review.

With its rising global prevalence, diabetes has become one of the most significant and challenging health problems afflicting the world's population today. The increasing burden of diabetes and its associated complications calls for immediate action for prevention which primarily includes addressing the risk factors. The most significant risk factor for the onset of diabetes is obesity. Obesity and diabetes rates have been rising simultaneously, posing a threat to patient mortality and driving up community healthcare costs. A weight loss of five percent or more of total body weight has been shown to improve the quality of life, reduce the need for pharmacological therapy for diabetes, and enhance glycemic control. This level of weight loss can have significant health benefits, particularly for individuals with diabetes or at risk for developing diabetes. We aim to conduct this systematic review to assess diverse risk factors contributing to the incidence of diabetes among the obese population and determine various preventive strategies and recommendations in practice for the prevention of diabetes in this cohort. As a result, we included original studies that recruited the obese and diabetic populations and defined preventive measures for early intervention. Additionally, we included studies published in the last 10 years (2014-2024) only for the latest evidence. Studies including obese populations with cardiovascular diseases and neurological disorders were excluded. The Newcastle-Ottoman Castle assessment tool was utilized to assess the quality of the studies. We included nine studies that recruited 60,645 patients and were published between 2015 and 2022. Findings suggest that obesity alone is a significant contributor to the occurrence or onset of diabetes. At the same time, the presence of other risk factors, including hypertension, dyslipidemia, elevated triglycerides, or HDL and LDL levels, may further increase the risk of diabetes and its associated complications among the obese population. Preventive strategies emphasize early intervention through increasing awareness and educating communities about risk factors and lifestyle interventions, including the limitations of fast food diets for the prevention of diabetes and weight control. Since obesity is considered to be an independent risk factor for the development of diabetes, addressing and managing it is of critical importance clinically. Targeted early interventions, including screening for risk factors, health promotion, and education activities, can aid in the adaptation of healthier lifestyles, which can reduce the burden of these diseases significantly.

Typical Hemolytic Uremic Syndrome Secondary to Influenza A in a Pediatric Patient With Complex Comorbidities: A Rare Encounter.

Hemolytic uremic syndrome (HUS) is a severe condition characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). It can be atypical, due to complement dysregulation, or typical, primarily linked to bacterial infections, with viral-induced HUS being extremely rare. We report the case of a six-year-old male who presented with eight days of upper respiratory tract infection symptoms. Initial treatment for tonsillitis was ineffective. He was admitted to the Pediatric Intensive Care Unit (PICU) with severe dehydration, high-grade fever, and AKI, and was initially suspected of having multi-system inflammatory syndrome in children (MIS-C). Further investigation confirmed typical HUS, likely secondary to Influenza A. The child required peritoneal dialysis and other supportive treatments until recovery. This case underscores the need to consider viral-induced HUS in pediatric patients with severe infections and complex medical presentations. An interdisciplinary approach and timely interventions were crucial for his recovery. This rare presentation of HUS associated with Influenza A highlights the importance of clinical awareness and the need for further research to improve care strategies for similar cases.

Trajectories of Sacubitril/Valsartan Adherence Among Medicare Beneficiaries With Heart Failure.

Background: Sacubitril/valsartan, an angiotensin receptor/neprilysin inhibitor (ARNi), improves heart failure (HF) outcomes, yet real-world adherence patterns are not well understood. Objectives: The purpose of this study was to analyze longitudinal patterns of adherence to ARNis in patients with HF and to identify factors associated with adherence patterns. Methods: Using Medicare beneficiaries from 2015 to 2018, we included patients diagnosed with HF who initiated an ARNi. A group-based trajectory model was constructed to identify adherence patterns during follow-up. We used multivariable logistic regression to investigate factors associated with membership in each adherence trajectory group. Results: Among 9,475 eligible beneficiaries (age 77 ± 7 years, 34% female), we identified 5 distinct ARNi adherence trajectories, characterized as: immediate discontinuers, who discontinued treatment within the first 3 months (12%); early discontinuers, who discontinued treatment in months 4 to 7 (10%); late discontinuers, who discontinued treatment in months 7 to 10 (12%); intermittently adherent patients (12%); and consistently adherent patients (54%). The first 4 groups were collectively categorized as nonconsistent adherents. Living in a socioeconomically disadvantaged area, ie, a county with the top 20% of Area Deprivation Index (adjusted OR [aOR]: 1.12 [95% CI: 1.00-1.24]) and Black race (aOR: 1.36, [95% CI: 1.18-1.56]) were associated with a higher likelihood of being nonconsistently adherent. Receiving prescriptions from a cardiologist (aOR: 0.64 [95% CI: 0.57-0.73]) was associated with a lower likelihood of suboptimal ARNi adherence. Conclusions: Half of ARNi users were not consistently adherent to the drug in the first year after treatment initiation. There exist significant racial and socioeconomic inequities in longitudinal adherence to ARNi.

Temporary mechanical support in the peripartum patient as a bridge to postpartum recovery: A report of three cases.

Cardiogenic shock (CS) is a severe complication of peripartum cardiomyopathy (PPCM). Patients with deteriorating CS often require temporary mechanical circulatory support. In PPCM, this can be used as a bridge to postpartum recovery or bridge to decision. The outcomes are unclear, especially if prolonged utilization is required. We present a case series of three patients with PPCM in deteriorating CS who were successfully supported with a ventricular assist device or veno-arterial extracorporeal membrane oxygenation as a bridge to postpartum recovery.

Mammary Paget's Disease as a Sign of Local Recurrence Two Decades Following Breast Conservation and Adjuvant Therapy for Early Stage Breast Cancer.

Reports of mammary Paget's disease (MPD) as a manifestation of breast cancer recurrence are rare. MPD presents a particular challenge when emerging more than two decades after a breast cancer treated with evidence-based therapy. There is a broad spectrum of non-malignant causes for dermatitis of the nipple during the initial presentation that may delay cancer work-up. This case highlights the MPD work-up and management in the context of a personal history of breast cancer. This unique clinical presentation emphasizes the importance of vigilant cancer surveillance for timely intervention, especially for a presumed cured cancer.

Demonstrating a Quartz Crystal Microbalance with Dissipation (QCMD) to Enhance the Monitoring and Mechanistic Understanding of Iron Carbonate Crystalline Films.

This paper reports the real time monitoring of siderite deposition, on both Au- and Fe-coated surfaces, using the changes in frequency and dissipation of quartz crystal microbalance with dissipation (QCMD). In an iron chloride solution saturated with carbon dioxide, buffered with sodium bicarbonate to pH 6.8, roughly spherical particles of siderite formed within 15 min, which subsequently deposited on the QCMD crystal surface. Imaging of the surface showed a layer formed from particles ca. < 0.5 µm in diameter. Larger particles are clearly deposited on top of the lower layer; these larger particles are >1 µm in diameter. Monitoring of the frequency clearly differentiates the formation of the lower layer from the larger crystals deposited on top at later times. The elastic moduli calculated from QCMD data showed a progressive dissipation increase; the modeling of the solid-liquid interface using a flat approximation resulted in a poor estimation of elastic and storage moduli. Rather, the impedance modeled as a viscoelastic layer in contact with a semi-infinite liquid, where a random bumpy surface with a Gaussian correlator is used, is much more accurate in determining the elastic and storage moduli as losses from the uneven interface are considered. A further step considers that the film is in fact a composite consisting of hard spherical particles of siderite with water in the vacant spaces. This is treated by considering the individual contributions of the phases to the losses measured, thereby further improving the accuracy of the description of the film and the QCMD data. Collectively, this work presents a new framework for the use of QCMD, paired with traditional approaches, to enhance the understanding of crystal deposition and film formation as well as quantify the often evolving mechanical properties.

Evaluation of Spirooxindole-3,3'-pyrrolines-incorporating Isoquinoline Motif as Antitumor, Anti-Inflammatory, Antibacterial, Antifungal, and Antioxidant Agents.

BACKGROUND: A series of novel 2-(isoquinolin-1-yl)-spiro[oxindole-3,3'-pyrrolines] were synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, 3- phenylimidazo[5,1-a]isoquinoline and N-alkylisatins in chloroform at ∼60 °C for 24 h. AIMS: This study aimed at the synthesis of novel spirooxindole-3,3'-pyrrolines derivatives and in vitro evaluation of cytotoxicity affinities in cross-correlations with their antiinflammation and radical scavenging capacities. OBJECTIVE: The objective of this study was to use a one-pot, three-component reaction to synthesize a novel set of spirooxindole-3,3'-pyrrolines derivatives. METHOD: A novel set of spirooxindole-3,3'-pyrrolines (8a-i) was synthesized by a one-pot threecomponent reaction involving dimethyl acetylenedicarboxylate, 3-phenylimidazo[5,1-a]isoquinoline and N-alkylisatins in chloroform at ∼60 °C for 24 h. These new compounds were characterized by 1HNMR, 13C-NMR, and HRMS spectral data and screened for their antitumor, anti-inflammatory, antibacterial, antifungal, and antioxidant activities. RESULTS: The new synthetic spirooxindole-3,3'-pyrrolines (8a-i)-tested compounds displayed significant anti-inflammatory properties and were noncytotoxic on PDL fibroblasts. However, they lacked antioxidative-DPPH radical scavenging capabilities. Notably, Doxorubicin and cisplatin demonstrated antiproliferative effects on various cancer monolayers. Moreover, compounds 8b, 8d, 8f, 8h, and 8i exhibited pronounced viability reduction properties in colorectal and pancreatic cancer monolayers, as well as across skin, lung, prostate, and cervical adenocarcinomas, with higher cytotoxicity in mammary cancer cells MCF7 and T47D. None of the tested compounds had significant antibacterial activity against S. aureus or E. coli. However, compounds 8c, 8d, and 8f exhibited notable antifungal properties, indicating potential for further investigation. CONCLUSION: Eight new synthetic spiro[indoline-3,3-pyrroles] were prepared, characterized, and evaluated for their anti-inflammatory and cytotoxic properties. The compounds showed significant anti-inflammatory effects and promising cytotoxicity against various cancer monolayers, especially in colorectal and pancreatic cancers. Some compounds also exhibited antifungal properties. However, they did not exhibit significant antibacterial activity.

Effects of Laccase and Transglutaminase on the Physicochemical and Functional Properties of Hybrid Lupin and Whey Protein Powder.

Plant-based protein is considered a sustainable protein source and has increased in demand recently. However, products containing plant-based proteins require further modification to achieve the desired functionalities akin to those present in animal protein products. This study aimed to investigate the effects of enzymes as cross-linking reagents on the physicochemical and functional properties of hybrid plant- and animal-based proteins in which lupin and whey proteins were chosen as representatives, respectively. They were hybridised through enzymatic cross-linking using two laccases (laccase R, derived from Rhus vernicifera and laccase T, derived from Trametes versicolor) and transglutaminase (TG). The cross-linking experiments were conducted by mixing aqueous solutions of lupin flour and whey protein concentrate powder in a ratio of 1:1 of protein content under the conditions of pH 7, 40 °C for 20 h and in the presence of laccase T, laccase R, or TG. The cross-linked mixtures were freeze-dried, and the powders obtained were assessed for their cross-linking pattern, colour, charge distribution (ζ-potential), particle size, thermal stability, morphology, solubility, foaming and emulsifying properties, and total amino acid content. The findings showed that cross-linking with laccase R significantly improved the protein solubility, emulsion stability and foaming ability of the mixture, whereas these functionalities were lower in the TG-treated mixture due to extensive cross-linking. Furthermore, the mixture treated with laccase T turned brownish in colour and showed a decrease in total amino acid content which could be due to the enzyme's oxidative cross-linking mechanism. Also, the occurrence of cross-linking in the lupin and whey mixture was indicated by changes in other investigated parameters such as particle size, ζ-potential, etc., as compared to the control samples. The obtained results suggested that enzymatic cross-linking, depending on the type of enzyme used, could impact the physicochemical and functional properties of hybrid plant- and animal-based proteins, potentially influencing their applications in food.

"Sigma-1 receptor modulation by clemastine highlights its repurposing as neuroprotective agent against seizures and cognitive deficits in PTZ-kindled rats".

Epilepsy is a neurological disorder characterized by recurrent spontaneous seizures alongside other neurological comorbidities. Cognitive impairment is the most frequent comorbidity secondary to progressive neurologic changes in epilepsy. Sigma 1 receptors (σ1 receptors) are involved in the neuroprotection and pathophysiology of both conditions and targeting these receptors may have the potential to modulate both seizures and comorbidities. The current research demonstrated the effect of clemastine (10 mg/kg, P.O.), a non-selective σ1 receptor agonist, on pentylenetetrazol (PTZ) (35 mg/kg, i.p., every 48 h for 14 doses)-kindling rats by acting on σ1 receptors through its anti-inflammatory/antioxidant capacity. Clemastine and phenytoin (30 mg/kg, P.O.) or their combination were given once daily. Clemastine treatment showed a significant effect on neurochemical, behavioural, and histopathological analyses through modulation of σ1 receptors. It protected the kindling animals from seizures and attenuated their cognitive impairment in the Morris water maze test by reversing the PTZ hippocampal neuroinflammation/oxidative stress state through a significant increase in inositol-requiring enzyme 1 (IRE1), x-box binding protein 1 (XBP1), along with a reduction of total reactive oxygen species (TROS) and amyloid beta protein (Aß). The involvement of σ1 receptors in the protective effects of clemastine was confirmed by their abrogation when utilizing NE-100, a selective σ1 receptor antagonist. In light of our findings, modulating σ1 receptors emerges as a compelling therapeutic strategy for epilepsy and its associated cognitive impairments. The significant neuroprotective effects observed with clemastine underscore the potential of σ1 receptor-targeted treatments to address both the primary symptoms and comorbidities of neurological disorders.