Soliman Khatib

Alzheimer’s disease (AD) is a neurodegenerative disorder marked by progressive cognitive decline. Despite extensive research, its multifactorial nature continues to challenge the development of effective therapies. Current treatments, including anticholinergic agents and amyloid β–targeted drugs, alleviate symptoms but fail to halt disease progression and often produce side effects. Therefore, novel multi-target strategies are urgently needed. Cannabis ( Cannabis sativa L. ) has long been recognized for its medicinal properties, yet its potential in AD therapy has only recently gained attention. Previous studies have mainly focused on single cannabinoids or endocannabinoid system modulation. In this study, we investigated whole cannabis flower extracts, rich in diverse active compounds, for their ability to inhibit key AD-related enzymes: acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE1), using spectrophotometric assays. Fractionation of one extract further identified components with potent inhibitory activity against both BChE and BACE1. Additionally, the extracts were evaluated for their cell-protective potential in PC12 cells exposed to hydrogen peroxide (H₂O₂) and amyloid β (Aβ₁–₄₂), mimicking AD-like oxidative stress conditions. Cannabis extracts showed stronger inhibition of cholinergic enzymes compared to Galantamine, with efficacy depending on extract composition. Importantly, this study is among the first to reveal significant BACE1 inhibition by cannabis extracts. Moreover, the extracts enhanced PC12 cell viability under oxidative stress, indicating cell-protective effects. Overall, these findings suggest that multi-component cannabis extracts may interact with several AD-related molecular targets in vitro and may serve as promising leads for further mechanistic and preclinical investigation.

The maternal microbiome during oogenesis is a critical but underappreciated regulator of offspring physiology. Using Drosophila melanogaster as a model, we show that a single, transient antibiotic exposure during oogenesis, without direct offspring exposure, is sufficient to reprogram larval behaviour, gene expression, and metabolism. Adult flies exposed to either ciprofloxacin or vancomycin produced third-instar larvae with significantly reduced crawling speed and a significantly higher prevalence of abnormal locomotion. Transcriptomic profiling revealed widespread downregulation of genes governing energy metabolism, particularly the tricarboxylic acid cycle, as well as cuticle development and protein folding. Metabolomic profiling identified elevation of L-norvaline across both antibiotic groups, and acute parental supplementation with L-norvaline alone recapitulated the observed crawling deficits, directly implicating this metabolite in the phenotype. These findings demonstrate that even brief disruption of the microbiome during oogenesis triggers a cascade of intergenerational physiological changes, establishing this window as a key period of microbiome-dependent offspring programming.

Cost-effective procedures usually cannot achieve complete removal of priority contaminants present in water at very low concentrations (as pesticides or pharmaceuticals). Advanced oxidation processes (AOPs) represent promising technologies for removing priority contaminants from water at trace concentrations, yet practical implementation remains limited due to technical and economic constraints. This study presents an innovative flow-through photodegradation device designed to overcome current limitations while achieving efficient contaminant removal at industrial scale. The device integrates a UVC 254 nm lamp-equipped flow chamber with automated dosing pumps for hydrogen peroxide and/or solid catalyst suspensions, coupled with a 30 nm porous membrane filtration system for catalyst recirculation. This configuration optimizes light–catalyst–pollutant contact while enabling combined catalytic processes. Performance evaluation using acesulfame (ACE) and iohexol (IHX) as model contaminants demonstrated rapid and effective removal. IHX degradation with UVC and 75 μM H₂O₂ achieved complete removal with t₉₅% = 7.23 ± 1.21 min (pseudo-order 0.25, t₁/₂ = 3.27 ± 0.39 min), while ACE photolysis (with UVC only) required t₉₅% = 14.88 ± 2.02 min (pseudo-order 1.27, t₁/₂ = 2.35 ± 0.84 min). The introduction of t₉₅% as a performance metric provides practical insights for near-complete contaminant removal requirements. Real-world efficacy was confirmed using tertiary wastewater treatment plant effluents containing 14 μg/L IHX, achieving complete removal within 8 min. However, carbamazepine degradation proved slower (t₉₅% > 74 h), highlighting the need for combined catalytic approaches for recalcitrant compounds. Spiking experiments (1000 μg/L) revealed concentration-dependent kinetics and synergistic effects between co-present contaminants. Analysis identified degradation byproducts consistent with previous studies, including tri-deiodinated iohexol (474.17 Da) intermediates. This scalable system, constructed from commercially available components, demonstrates potential for cost-effective industrial implementation. The modular design allows adaptation to various contaminants through adjustable AOP combinations (UV/H₂O₂, photocatalysts, ozone), representing a practical advancement toward addressing the gap between laboratory-scale photocatalytic research and full-scale water treatment applications.

Cost-effective procedures usually can't achieve complete removal of priority contaminants present in water at very low concentrations (as pesticides or pharmaceuticals). Advanced oxidation processes (AOPs) represent promising technologies for removing priority contaminants from water at trace concentrations, yet practical implementation remains limited due to technical and economic constraints. This study presents an innovative flow-through photocatalytic device designed to overcome current limitations while achieving efficient contaminant removal at industrial scale. The device is integrates a UVC 254nm lamp-equipped flow chamber with automated dosing pumps for hydrogen peroxide and/or solid catalyst suspensions, coupled with a 30 nm pores membrane filtration system for catalyst recirculation. This configuration optimizes light-catalyst-pollutant contact while enabling combined catalytic processes. Performance evaluation using acesulfame (ACE) and iohexol (IHX) as model contaminants demonstrated rapid and effective removal. IHX degradation with UVC and 75 μM H₂O₂ achieved complete removal with t₉₅% = 7.23±1.21 minutes (pseudo-order 0.25, t₁/₂ = 3.27±0.39 min), while ACE photolysis (with UVC only) required t₉₅% = 14.88±2.02 minutes (pseudo-order 1.27, t₁/₂ = 2.35±0.84 min). The introduction of t₉₅% as a performance metric provides practical insights for near-complete contaminant removal requirements. Real-world efficacy was confirmed using tertiary wastewater treatment plant effluents containing 14 μg/L IHX, achieving complete removal within 8 minutes. However, carbamazepine degradation proved slower (t₉₅% > 74 hours), highlighting the need for combined catalytic approaches for recalcitrant compounds. Spiking experiments (1000 μg/L) revealed concentration-dependent kinetics and synergistic effects between co-present contaminants. Analysis identified degradation byproducts consistent with previous studies, including tri-deiodinated iohexol (474.17 Da) intermediates. This scalable system, constructed from commercially available components, demonstrates potential for cost-effective industrial implementation. The modular design allows adaptation to various contaminants through adjustable AOP combinations (UV/H₂O₂, photocatalysts, ozone), representing a practical advancement toward addressing the gap between laboratory-scale photocatalytic research and full-scale water treatment applications.

Olive Mill Solid Waste (OMSW) presents an environmental challenge due to its toxicity and difficulties in its recycling. Prior studies suggest its potential as a substrate ingredient for cultivating edible mushrooms. Here, we investigate how varying OMSW concentrations in the substrate affect the synthesis pathways of α-glucan and β-glucan polysaccharides, alongside transcriptional and metabolic changes in Pleurotus eryngii. We also assessed the mushroom’s protein and nitrogen content. Our results highlight the critical role of substrate composition, demonstrating that the OMSW concentration significantly influences mushroom growth, yield, protein content, gene expression, and metabolite profiles. These findings establish OMSW not only as a viable recycling resource but also as a modulator of health-promoting compound synthesis in P. eryngii.

Epilepsy is a widespread neurological disorder that remains a critical global public health challenge. While numerous antiepileptic drugs (AEDs) are available, many patients either fail to achieve adequate seizure control or experience significant side effects. One promising alternative is pure cannabidiol (CBD), but using a whole cannabis extract may be equally effective and preferred for some patients. In the current study, we employed the pentylenetetrazole (PTZ)-induced hyperactivity model in zebrafish to compare the effects of CBD with various cannabis extracts. We evaluated three cannabis strains, each subjected to three different extraction methods, and benchmarked the results against the commercially available AED valproic acid (VPA). Our findings revealed that 5.7 µg/mL of CBD and 10 µg/mL of different extracts significantly reduced movement compared to PTZ and VPA. In addition, effective extracts produced effects similar to pure CBD despite containing much lower molecule levels. These results reinforced and expanded previous evidence supporting the clinical potential of both CBD and whole cannabis extracts for seizure control while suggesting a possible entourage effect. Further research is necessary to determine which patients may benefit more from pure CBD versus those who might prefer whole cannabis extracts.

Introduction: Mushrooms contain besides proteins a diverse pallet of specialized metabolites bioactive in either beneficial or harmful manner. Therefore, mushrooms have been exploited by humans for centuries for dietary or medical purposes. For example, the edible and medicinal mushrooms Hericium erinaceus and Pleurotus eryngii are grown commercially around the world. In nature, H. erinaceus grows on old or dead tree trunks, and P. eryngii grows on Apiaceae plant roots, whereas in cultivation, they grow on substrates mainly consisting of dry wood chips, straw, and cereals. To make their farming more sustainable, supplements such as olive mill solid waste (OMSW) have been added to support mushroom development. However, so far, the impact of substrate additives on the edible mushroom metabolic content has not been assessed. Methods: Here, we examined the effect of different proportions of OMSW added to the substrate on the metabolic profiles of the fruiting body (FB) and mycelium of H. erinaceus and P. eryngii mushrooms. The study includes four groups for each mushroom species, mushrooms are grown on 0% OMSW, 33%, 60%, and 80% OMSW, with three biological repeats in each group. We used computational metabolomics strategies including GNPS molecular networking, MS2Query, and the FERMO dashboard, to organize, annotate, and prioritize metabolite features from the untargeted Q-Exactive Plus HR-LC-MS/MS metabolomics data. Following chromatography-based fractionation, the metabolite annotation of four metabolite features was further validated or fine-tuned using ¹H-NMR, to resolve structural isomers. Results and discussion: Our computational metabolomics strategies showed several annotated metabolite features to be affected by OSMW concentration. In general, the methanolic extracts of H. erinaceus FB and mycelium were more highly enriched with specialized metabolites than those of P. eryngii. Interestingly, OMSW increased several hericenone analogues in the H. erinaceus FB, as well as several erinacerin metabolites from the mycelium. In addition, high concentrations of OMSW decreased the enniatin metabolite abundance. In conclusion, we demonstrate how a change in substrate composition affects the mushroom’s specialized metabolome and can induce and alter mushroom metabolite content and diversity. These results highlight the importance of including computational metabolomic strategies to investigate new sustainable growth options for edible mushrooms and other natural foods.

Atherosclerosis is a major cause of morbidity and mortality worldwide; in Israel, ischemic heart disease is the second leading cause of death for both genders aged 45 and above. Atherosclerosis involves stiffening of the arteries due to the accumulation of lipids and oxidized lipids on the blood vessel walls, triggering the development of artery plaque. Coronary artery disease (CAD) is the most common manifestation of atherosclerosis. The prevalence of CAD in the general population remains high, despite efforts to improve the identification of risk factors and preventive treatments. The discovery of new biomarkers is vital to improving the diagnosis of CAD and its risk factors. We aimed to identify novel biomarkers that could provide an early diagnosis of coronary artery atherosclerotic plaques, their type, and the percentage of stenosis. We used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAD detection. The study consisted of 109 patients who underwent cardiac computed tomography angiography at the Cardiology Department of Ziv Medical Center. Fifty‐four patients were diagnosed with coronary atherosclerotic plaques (CAD group), and 55 without plaques used control. Untargeted metabolomics using LC–MS/MS revealed 2560 metabolites in the patients' serum: 106 showed statistically significant upregulation in the serum of the CAD group compared with the healthy control group ( p < 0.05). These metabolites belonged to the following chemical families: acyl‐carnitines, cyclodipeptides, lysophosphatidylcholine, and primary bile acids. In contrast, 98 metabolites displayed statistically significant downregulation in the serum of the CAD group compared with the control group, belonging to the following chemical families: GABA amino acids and derivatives (inhibitory neurotransmitters), lipids, and secondary bile acids. Our comprehensive untargeted serum metabolomic analysis revealed biomarkers that can be used for the diagnosis of patients with CAD. Further cohort studies with a larger number of participants are needed to validate the detected biomarkers.

Epilepsy is a widespread neurological disorder that remains a critical global public health challenge. While numerous antiepileptic drugs (AEDs) are available, many patients either fail to achieve adequate seizure control or experience significant side effects. One promising alternative is pure cannabidiol (CBD), but using a whole cannabis extract may be equally effective and preferred for some patients. In the current study, we employed the pentylenetetrazole (PTZ)-induced hyperactivity model in zebrafish to compare the effects of CBD with various cannabis extracts. We evaluated three cannabis strains, each subjected to three different extraction methods, and benchmarked the results against the commercially available AED valproic acid (VPA). Our findings revealed that 5.7 µg/ml of CBD and 0.01 mg/ml of different extracts significantly reduced movement compared to PTZ and VPA. In addition, effective extracts produced similar effects to pure CBD despite containing much lower molecule levels. These results reinforced and expanded previous evidence supporting the clinical potential of both CBD and whole cannabis extracts for seizure control while suggesting a possible entourage effect. Further research is necessary to determine which patients may benefit more from pure CBD versus those who might prefer the whole cannabis extracts.