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19 pages, 6011 KB  
Article
Tetrahydrocurcumin Attenuates NaIO3-Induced Retinal Oxidative Injury via Suppression of NOX2-Derived ROS-Mediated Apoptosis
by Tzu-Chun Chen, Thuy-Lan-Thi Vo, Shang-Chun Tsou, Hui-Min David Wang, Inga Wang, Chen-Ju Chuang, Hui-Wen Lin and Yuan-Yen Chang
Antioxidants 2026, 15(6), 765; https://doi.org/10.3390/antiox15060765 (registering DOI) - 18 Jun 2026
Viewed by 173
Abstract
Oxidative stress is a major contributor to the development of age-related macular degeneration (AMD), and excessive oxidative stress can induce retinal pigment epithelium (RPE) dysfunction, apoptosis, and retinal degeneration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is a major enzymatic source of [...] Read more.
Oxidative stress is a major contributor to the development of age-related macular degeneration (AMD), and excessive oxidative stress can induce retinal pigment epithelium (RPE) dysfunction, apoptosis, and retinal degeneration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is a major enzymatic source of reactive oxygen species (ROS); however, its mechanistic role in sodium iodate (NaIO3)-induced oxidative injury remains unclear. Tetrahydrocurcumin (THC), the major metabolite of curcumin, exhibits potent antioxidant and cytoprotective activities, but its protective effects against AMD-associated retinal degeneration have not been fully elucidated. In the present study, we investigated whether THC protects against NaIO3-induced ROS-mediated apoptosis in RPE cells through regulation of NOX2 signaling. In vitro, THC significantly attenuated NaIO3-induced cytotoxicity and prevented apoptosis by suppressing hydrogen peroxide (H2O2) production and intracellular ROS accumulation in ARPE-19 cells. THC also preserved mitochondrial membrane potential by inhibiting the Src/p47phox/NOX2 signaling pathway and subsequently attenuated mitochondria-mediated apoptotic signaling. Furthermore, THC markedly reduced the expression of apoptotic proteins, including Bax, cleaved caspase-3, and cleaved PARP, concomitantly with suppression of Ras/Raf/MEK/ERK signaling. Mechanistically, treatment with the selective NOX2 inhibitor GSK2795039 significantly attenuated NaIO3-induced ROS accumulation and mitochondrial depolarization, while co-treatment with THC further enhanced these protective effects. In vivo, THC ameliorated NaIO3-induced retinal structural abnormalities by preserving the outer nuclear layer (ONL), reducing caspase-3 expression, and improving pupillary light responses in mice. Collectively, these findings demonstrate that THC protects against NaIO3-induced retinal degeneration through suppressing NOX2-dependent oxidative stress and downstream Ras/Raf/MEK/ERK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for AMD and other oxidative stress-related retinal disorders. Full article
(This article belongs to the Special Issue Antioxidants and Retinal Diseases—2nd Edition)
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28 pages, 607 KB  
Article
Comparative Analysis of the Chemical Composition of Hemp and Linseed Varieties as Key Industrial Commodities
by Tomáš Taubner, Michaela Englmaierová, Marie Bjelková, Věra Skřivanová, Klára Bejčková, Tomáš Vít and Kateřina Růnová
Foods 2026, 15(12), 2145; https://doi.org/10.3390/foods15122145 - 14 Jun 2026
Viewed by 236
Abstract
Hemp and linseed are nutritionally valuable commodities that exhibit considerable varietal differences in composition. Nutrient composition was evaluated in 12 hemp and 11 linseed varieties, including commercially cultivated varieties from the EU Common Catalogue and newly bred lines, to assess varietal variability. Field [...] Read more.
Hemp and linseed are nutritionally valuable commodities that exhibit considerable varietal differences in composition. Nutrient composition was evaluated in 12 hemp and 11 linseed varieties, including commercially cultivated varieties from the EU Common Catalogue and newly bred lines, to assess varietal variability. Field experiments were conducted under uniform agronomic conditions in the Czech Republic during a single growing season using field-block samples. Analyses included proximate composition (dry matter, crude protein, fat, fiber, ash), fatty acid and amino acid profiles, carotenoids, vitamins, and cannabinoid content. Statistical evaluation was performed using a General Linear Model with Duncan’s multiple range test (p < 0.05). Significant differences were observed across most parameters, indicating substantial inter-varietal variability under the experimental conditions. Fat content ranged from approximately 200 to 377 g/kg in both oilseeds, with lipids dominated by polyunsaturated fatty acids, particularly linoleic (n-6) and α-linolenic (n-3) acids. Hemp and linseed show potential as alternative plant protein sources in animal nutrition, but further digestibility and feeding studies are needed to confirm their suitability as partial soybean meal substitutes. Varietal selection may contribute to improved nutritional quality while influencing levels of undesirable constituents such as Δ9-THC in hemp. Full article
(This article belongs to the Section Food Nutrition)
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16 pages, 1734 KB  
Article
Influence of 3D Printer Type, Resin Material, Thickness, and Geometry on the Mechanical Properties of Directly Printed Clear Aligners
by Fırat Oğuz, Sabahattin Bor, Buse Çebi Gül and Handan Göze Oğuz
Polymers 2026, 18(12), 1486; https://doi.org/10.3390/polym18121486 - 13 Jun 2026
Viewed by 319
Abstract
To evaluate the effects of three different 3D printers, two clear aligner resins, two specimen thicknesses, two lengths, and two geometric designs on the tensile strength and elastic modulus of directly printed clear aligners. Specimens were produced from two orthodontic aligner resins, Clear [...] Read more.
To evaluate the effects of three different 3D printers, two clear aligner resins, two specimen thicknesses, two lengths, and two geometric designs on the tensile strength and elastic modulus of directly printed clear aligners. Specimens were produced from two orthodontic aligner resins, Clear A (Senertek, Izmir, Turkey) and Tera Harz TA 28 (Graphy Inc., Seoul, Republic of Korea), using three different 3D printers: Ackuretta SOL (LCD), Asiga MAX (DLP), and UNIZ NBEE (LCD). Specimens were designed in two forms (dumbbell, in accordance with ISO 527 3, and flat strip), in two thicknesses (0.5 mm and 1 mm), and in two lengths (short and long), yielding 24 groups with 5 specimens each (n = 120). All specimens were post processed using the Tera Harz Spinner and cured for 25 min under nitrogen atmosphere in the THC 2 MC unit, followed by a 1 min boiling water treatment. Tensile tests were performed on a universal testing machine (Shimadzu Corp., Kyoto, Japan) up to fracture. Maximum force (N) and elastic modulus (N/mm2) were recorded. Data were analyzed using Kruskal–Wallis, Mann–Whitney U, and Aligned Rank Transform ANOVA tests with Dunn post hoc and Bonferroni correction (p < 0.05). Printer type had no significant effect on maximum force (p = 0.357) or elastic modulus (p = 0.052). Resin type (p < 0.001), thickness (p < 0.001), and specimen geometry (p < 0.001) showed significant effects on both parameters. TA 28 specimens exhibited higher mechanical performance than Clear A. Increased thickness produced higher maximum force and elastic modulus values. Flat geometries showed the highest maximum force, while the short dumbbell exhibited the lowest. The long thin dumbbell geometry yielded the highest elastic modulus values. Resin composition, thickness, and specimen geometry are the primary determinants of mechanical performance in directly printed clear aligners, whereas printer type appears to play a limited role. Full article
(This article belongs to the Section Polymer Applications)
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13 pages, 1763 KB  
Article
CNR1 and CNR2 Cannabinoid Receptor Mutations in Cancer Cells
by Lillian Schneider, Maria Ruano, Camryn R. Mackey, Kiersten Spiegel, Renee A. Bouley, Ruben C. Petreaca and Ryan J. Yoder
Curr. Issues Mol. Biol. 2026, 48(6), 610; https://doi.org/10.3390/cimb48060610 - 11 Jun 2026
Viewed by 158
Abstract
Cannabinoids, including the psychoactive D9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD), interact with receptors within the endocannabinoid system. The major receptors within this system are CNR1 (cannabinoid receptor 1) and CNR2 (cannabinoid receptor 2), which are both seven-transmembrane G-protein-coupled receptors. In this report, [...] Read more.
Cannabinoids, including the psychoactive D9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD), interact with receptors within the endocannabinoid system. The major receptors within this system are CNR1 (cannabinoid receptor 1) and CNR2 (cannabinoid receptor 2), which are both seven-transmembrane G-protein-coupled receptors. In this report, we used the Catalogue of Somatic Mutations in Cancers (COSMIC) to map and analyze mutations arising in CNR1 and CNR2. The goal was to determine if any trends or signatures could be identified. We identified several mutations in both CNR1 and CNR2. In silico 3D structure of proteins reveals that these mutations cluster on the intracellular regions of CNR1 and CNR2, and certain residues may be able to destabilize the interaction with the G-alpha protein due to their close proximity. mRNA expression showed that CNR1 and CNR2 are within normal expression levels in most cancer types except kidney, where there is a tendency towards over-expression. Neither CNR1 nor CNR2 is a driver gene, and our analysis shows that mutations in cancer cells are deactivating (e.g., loss of function). Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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15 pages, 419 KB  
Review
The Effects of Human Caring Theory-Based Interventions on Women’s Mental Health: A Systematic Review
by Şehma Şen and Şeyma Demiralay
Healthcare 2026, 14(12), 1658; https://doi.org/10.3390/healthcare14121658 - 11 Jun 2026
Viewed by 161
Abstract
Background/Objectives: This systematic review aims to synthesize existing evidence on the impact of nursing interventions based on Watson’s Theory of Human Caring (THC) on women’s mental health and to provide an evidence-based framework for clinical practice. Methods: The review followed the [...] Read more.
Background/Objectives: This systematic review aims to synthesize existing evidence on the impact of nursing interventions based on Watson’s Theory of Human Caring (THC) on women’s mental health and to provide an evidence-based framework for clinical practice. Methods: The review followed the PRISMA guidelines and was registered in the PROSPERO database (Registration No: CRD420251111577). A comprehensive literature search was conducted across databases, including PubMed, CINAHL, and Google Scholar. Ten studies (nine randomized controlled trials and one quasi-experimental study), involving 869 participants, met the eligibility criteria. Data were analyzed using a narrative synthesis approach due to methodological and clinical heterogeneity. Results: A total of 10 studies involving 894 women met the inclusion criteria. Geographically, nine studies were conducted in Türkiye and one in Iran. The included studies spanned various clinical contexts directly associated with significant mental health challenges for women, including medical abortion, infertility, gynecological oncology, and the postpartum period. The synthesized findings demonstrated that nursing interventions based on Watson’s Human Caring Theory led to statistically significant reductions in anxiety, depression, stress, postpartum depression risk, and infertility-related distress. Furthermore, these caritas-based frameworks significantly enhanced positive psychological assets, including self-efficacy, hope, meaning in life, prenatal attachment, and social support perception. Conclusions: Watson’s Theory of Human Caring provides a transformative framework for women’s health nursing that extends beyond symptom management to strengthen the individual’s internal resources and spiritual integrity. Integrating this theory into clinical protocols and nursing curricula is essential for humanizing care and protecting women’s mental health during challenging life transitions, particularly within the examined sociocultural contexts. Full article
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20 pages, 1183 KB  
Article
Antioxidant, Redox, and Immunomodulatory Effects of Hypericum perforatum in the Galleria mellonella: A 3R-Oriented Invertebrate Model
by Fatih Battal, Serhat Kaya and Hasan Ali Kiraz
Biomedicines 2026, 14(6), 1297; https://doi.org/10.3390/biomedicines14061297 - 7 Jun 2026
Viewed by 346
Abstract
Background/Objectives: Hypericum perforatum L. (St. John’s Wort) is extensively utilized in ethnopharmacology due to its anti-inflammatory and immunomodulatory properties. However, its effects on the interaction between innate immunity and oxidative homeostasis remain incompletely characterized, particularly in alternative invertebrate models. This study aimed [...] Read more.
Background/Objectives: Hypericum perforatum L. (St. John’s Wort) is extensively utilized in ethnopharmacology due to its anti-inflammatory and immunomodulatory properties. However, its effects on the interaction between innate immunity and oxidative homeostasis remain incompletely characterized, particularly in alternative invertebrate models. This study aimed to evaluate the effects of H. perforatum extract on oxidative homeostasis and protein metabolism using the Galleria mellonella model, a 3R-compliant and ethically sustainable platform for preliminary immunological and redox-related screening. Methods: Last instar G. mellonella larvae were administered increasing concentrations of H. perforatum extract (0.001–20 mg mL−1) by intrahemocoelic injection. After 24 h, hemolymph samples were analyzed for total protein (TP), total hemocyte count (THC), encapsulation and melanization responses, superoxide dismutase (SOD) activity, catalase (CAT) activity, and malondialdehyde (MDA) levels. The phytochemical profile of the extract was additionally evaluated using GC–MS analysis. Results: Significant group-dependent alterations were observed in TP levels and THC values, with the HP-2 group demonstrating the highest hemocyte counts and enhanced strong encapsulation responses. Higher extract concentrations, particularly HP-4, were associated with increased weak encapsulation profiles, suggesting altered cellular immune organization. Melanization responses became significantly elevated at 24 h following treatment. In contrast, SOD activity, CAT activity, and MDA levels did not differ significantly among groups, indicating preservation of oxidative homeostasis under the tested conditions. Conclusions: H. perforatum extract induced dose-dependent modulation of cellular and humoral immune responses in G. mellonella without evidence of detectable oxidative disruption during acute exposure. These findings support the utility of the G. mellonella model for preliminary evaluation of botanical immunomodulators and suggest that H. perforatum may influence immunophysiological pathways independently of overt oxidative toxicity. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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18 pages, 4751 KB  
Article
Preparation and Catalytic Performance Study of TiO2-Based Composite Photocatalysts Containing Natural Green CQDs
by Faxue Ma, Zhen Ma, Xiangju Wu, Xueqing Zhu, Yuguang Lv and Yukang Sun
Molecules 2026, 31(11), 1898; https://doi.org/10.3390/molecules31111898 - 1 Jun 2026
Viewed by 310
Abstract
Semiconductor photocatalysis technology is a simple, efficient, and low-cost method for environmental pollution remediation. As a promising photocatalyst for oxidative degradation, titanium dioxide (TiO2) demonstrates the capability to address energy shortages and environmental pollution issues. In this study, orange peel was [...] Read more.
Semiconductor photocatalysis technology is a simple, efficient, and low-cost method for environmental pollution remediation. As a promising photocatalyst for oxidative degradation, titanium dioxide (TiO2) demonstrates the capability to address energy shortages and environmental pollution issues. In this study, orange peel was used as the raw material to synthesize a (TiO2-CdS-C3N4-CDs) TCCC composite photocatalyst containing natural green carbon dots via a one-pot hydrothermal method for the first time. This catalyst was applied to the catalytic degradation of multiple dye molecules (Rhodamine B, Methylene Green, Reactive Brilliant Blue KN-R) and quinolone antibiotic (Ciprofloxacin, CIP) as well as tetracycline antibiotic (Tetracycline, THC). Meanwhile, it provides more adsorption sites for target pollutants and loads electron reservoirs (CDs) on the TCC surface, promoting the separation of photogenerated carriers in pure TiO2, thereby enhancing the visible light utilization and photocatalytic activity of the material. This work expands the application scope of semiconductor photocatalysis technology and TiO2-based photocatalytic active substrates. Full article
(This article belongs to the Special Issue Photocatalysts: Design, Synthesis, and Applications)
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22 pages, 2646 KB  
Article
Long-Term Inhaled Cannabis Therapy for Chronic Low Back Pain: A Five-Year Retrospective Analysis of Prospectively Collected Patient-Reported Outcomes in 241 Treatment-Refractory Patients
by Dror Robinson, Muhammad Khatib, Eitan Lavon, Niv Kafri, Waseem Abu Rashed, Hamza Murad and Mustafa Yassin
Biomedicines 2026, 14(6), 1255; https://doi.org/10.3390/biomedicines14061255 - 30 May 2026
Viewed by 416
Abstract
Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population and is a leading cause of years lived with disability. Long-term, real-world evidence for inhaled cannabis in patients refractory to conventional multimodal therapy remains scarce. We assessed the five-year efficacy [...] Read more.
Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population and is a leading cause of years lived with disability. Long-term, real-world evidence for inhaled cannabis in patients refractory to conventional multimodal therapy remains scarce. We assessed the five-year efficacy and safety of inhaled cannabis in CLBP patients who had documented failure of ≥1 year of opioid analgesics, anticonvulsants, antidepressants, NSAIDs, and physiotherapy, with each patient serving as their own historical control. Methods: We analyzed prospectively collected clinical data from 241 consecutive adults with treatment-refractory CLBP (mean age 49.3 ± 14.9 years; 37.8% female; mean pain duration 15.1 years) initiated on inhaled medical cannabis (predominantly smoking, THC 4–22%, CBD 2–22%) in a single-center tertiary orthopedic clinic between 2020 and 2025 (Hasharon Hospital, Rabin Medical Center, Israel; IRB protocols 0807-21-RMC and 0634-25-RMC). Year-0 outcomes during conventional therapy were compared with outcomes at Years 1–5 on cannabis. Primary outcomes were the Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and Brief Pain Inventory severity/interference (BPI-S/BPI-I). Concomitant-medication trajectories were a secondary outcome. The primary analysis was a mixed model for repeated measures (MMRM) with random intercept and slope, REML estimation, and time as a categorical fixed effect. Multiple imputation (MAR, m = 20, Rubin’s rules) was the primary missing-data approach; complete-case and tipping-point pattern-mixture sensitivity analyses were used. A multivariate Hotelling T2 provided a joint test across the four correlated PROMs. Concomitant-medication discontinuation was modeled with GEE logistic regression and exact McNemar tests. Time to discontinuation was estimated by Kaplan–Meier and Cox regression. The Bonferroni-adjusted significance threshold for the four primary outcomes was α = 0.0125. BioWell gas-discharge-visualization (GDV) parameters were exploratory only. Results: Of 241 patients, 238 (98.8%) provided Year-5 data and 224 (92.9%) remained on cannabis at Year 5; only five patients (2.1%) discontinued for adverse events or inefficacy. All four primary PROMs improved markedly and durably. MMRM-estimated Year-5 minus Year-0 changes were: NRS −5.36 (95% CI −5.65, −5.07), ODI −17.68 (95% CI −19.73, −15.63), BPI-S −6.73 (95% CI −6.99, −6.47), and BPI-I −3.41 (95% CI −3.65, −3.16); all four contrasts had |z| ≥ 16.9 and p < 10−20. MI-pooled estimates were within 0.05 of MMRM (FMI < 0.03 for all outcomes). Hotelling T2 was F(4, 232) = 872.8, p < 10−20. At Year 5, 89.2% achieved ≥30% NRS reduction, 77.2% ≥ 50%, and 93.4% met the NRS minimum clinically important difference (MCID); ODI MCID 65.6%, BPI-S MCID (≥1 pt) 98.3%, BPI-I MCID (≥1 pt) 91.3%. Concomitant opioid use fell from 100% at baseline to 4.6% at Year 5 (within-patient absolute risk reduction 95.4%, McNemar exact p = 1.16 × 10−69), NSAID from 100% to 7.1%, SSRI/SNRI from 80.5% to 5.4%, and gabapentinoid from 38.6% to 2.5%. The ARR-derived NNT for opioid discontinuation was 1.05; this NNT is referenced to each patient’s own documented maximal-conventional-therapy state and is not equivalent to a between-arm randomized-trial NNT. Cannabis dose × time interaction was consistent with no pharmacological tolerance (β = −0.0044 per gram-month per year, p = 0.074). Across 1205 patient-years of cannabis exposure (calculated as 241 patients × 5 follow-up years from Year 1 through Year 5; baseline Year 0 represents pre-cannabis state and is not included in person-time on cannabis), 1338 organ-system AE events were recorded at 1.110/patient-year (Poisson 95% CI 1.05–1.17); 99.8% of graded events were mild (grade 1), with ocular (476 events, 0.40/PY), cognitive (460, 0.38/PY), and gastrointestinal (368, 0.31/PY) reactions predominating. The Year-3 retention dip reflected a documented telemedicine-clinic phenomenon during 2022–2024, with patients returning to in-person follow-up by Year 4–5. BioWell GDV discriminated NRS ≥ 4 only at chance level (BWS AUC 0.574, 95% CI 0.54–0.60; BWV AUC 0.51). Conclusions: In a treatment-refractory CLBP cohort with five-year longitudinal follow-up, inhaled cannabis was associated with large, sustained, and statistically robust improvements in pain, disability, and pain interference, accompanied by near-total displacement of opioids, NSAIDs, antidepressants, and gabapentinoids. These observational associations, although mechanically less susceptible to bias for the binary medication-discontinuation outcomes than for self-reported PROMs, cannot be interpreted causally in the absence of a concurrent randomized control arm and may reflect a combination of pharmacological effect, regression to the mean from a high pre-treatment baseline, expectancy and self-selection effects intrinsic to an actively chosen open-label therapy, and secular trends in pain reporting. The within-patient benefit-risk profile—ARR-derived NNT ≈ 1 for opioid sparing against a predominantly mild adverse-event burden—supports consideration of cannabis as a potentially clinically meaningful, opioid-sparing option in patients who have failed multimodal conventional therapy, pending confirmation in randomized comparative trials. Full article
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23 pages, 2097 KB  
Review
Selected Cannabinoids, Cannabimimetic Agents and Artemisia Combinations as Theoretical Adjunct Strategies Against COVID-19
by Harry Chiririwa
Pharmaceuticals 2026, 19(6), 869; https://doi.org/10.3390/ph19060869 - 30 May 2026
Viewed by 347
Abstract
COVID-19 has spurred much interest in complementary and alternative agents for therapeutic purposes having antiviral and immunomodulatory effects. In these, natural products and bioactive compounds from plants have been at the center of attention due to their easy access, relatively low risk and [...] Read more.
COVID-19 has spurred much interest in complementary and alternative agents for therapeutic purposes having antiviral and immunomodulatory effects. In these, natural products and bioactive compounds from plants have been at the center of attention due to their easy access, relatively low risk and long history of use in traditional medicine. This paper reviews in detail and critically assesses the scientific data that presently proposes the use of certain cannabinoids, cannabimimetic compounds and Artemisia species in the treatment and prevention of COVID-19. It gives an account of medicinal approaches to cannabinoids like cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) alongside other minor cannabinoids and synthetic and naturally-occurring cannabimimetics. The paper reports the potential of Artemisia annua and other species as treatments, especially focusing on their antiviral, anti-regulatory, anti-inflammatory and immunomodulating properties. It highlights the molecular interactions with SARS-CoV-2 targets as well as cytokine regulation and modulation of oxidative stress pathways, with special emphasis on these areas. The paper raises multiple issues like preclinical and clinical studies, safety aspects, regulatory hurdles and drawbacks related to the use of these natural compounds. After analyzing all the available data, the article entertains the idea of a cannabinoid–Artemisia combination as a supportive or adjunct therapy in COVID-19 treatment. It also points out that the clinical trials are insufficient concerning the establishment of effectiveness, determination of the appropriate dosage and assurance of the long-term safety of the treatment. Full article
(This article belongs to the Special Issue The Therapeutic Potential of Cannabidiol)
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17 pages, 1234 KB  
Article
Non-Psychoactive Cannabis Extract Disrupts Reinstatement and Reconsolidation in Cocaine-Induced Conditioned Place Preference in Mice
by Fabián Leonardo Barreto, María Constanza Lozano, Yoshie Adriana Hata, Aura Rocio Hernández and Jorge A. Martínez-Ramírez
Brain Sci. 2026, 16(6), 585; https://doi.org/10.3390/brainsci16060585 - 29 May 2026
Viewed by 254
Abstract
Background: Cocaine use disorder (CUD) remains a major global health concern, with no FDA-approved pharmacological treatments currently available. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has shown promising preclinical effects in disrupting the consolidation and retrieval of drug-associated memories, thereby [...] Read more.
Background: Cocaine use disorder (CUD) remains a major global health concern, with no FDA-approved pharmacological treatments currently available. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has shown promising preclinical effects in disrupting the consolidation and retrieval of drug-associated memories, thereby attenuating relapse-like behaviors. Objectives: The present study evaluated the effects of a low-THC CBD-rich cannabis extract (NPCE) on the reinstatement and reconsolidation of cocaine-induced conditioned place preference (CPP) in male CD1 (ICR) mice, an approach not previously investigated. Methods: The extract was administered at a dose equivalent to 20 mg/kg of CBD. Treatment significantly attenuated both priming- and stress-induced reinstatement of cocaine-induced CPP. Reinstatement was triggered either by a cocaine priming injection or by acute stress exposure, whereas reconsolidation-like processes were assessed by administering the extract following memory reactivation sessions and subsequently evaluating the persistence of cocaine-associated preference over time. Results: NPCE showed a consistent result with disruption of reconsolidation-like processes of cocaine-associated memory, with effects persisting for at least two weeks. The extract alone did not induce conditioned preference or aversion. Conclusions: These findings suggest that NPCE modulates drug-associated memory processes involved in relapse-like behavior. However, the underlying mechanisms were not directly evaluated and remain to be elucidated. Further studies are warranted to include both sexes, evaluate effects across multiple behavioral paradigms, directly compare full-spectrum extracts with isolated cannabinoids, and incorporate receptor-specific approaches to clarify the mechanisms of action. Full article
(This article belongs to the Special Issue Substance Use and Addiction: From Molecular Mechanisms to Treatment)
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16 pages, 10468 KB  
Article
Characterization of Lithium-Ion Battery Fire Emissions—Part 3: Gas Emissions
by Matthew Claassen, Bjoern Bingham, Joseph Ammatelli, Judith C. Chow, John G. Watson, Yan Wang and Xiaoliang Wang
Batteries 2026, 12(6), 193; https://doi.org/10.3390/batteries12060193 - 27 May 2026
Viewed by 448
Abstract
Lithium-ion batteries (LIBs) release significant amounts of toxic, corrosive, and flammable gases when they enter thermal runaway (TR). These emissions can be hazardous to human health, damage nearby equipment, pose fire and explosion risks, and degrade air quality. This study measured concentrations for [...] Read more.
Lithium-ion batteries (LIBs) release significant amounts of toxic, corrosive, and flammable gases when they enter thermal runaway (TR). These emissions can be hazardous to human health, damage nearby equipment, pose fire and explosion risks, and degrade air quality. This study measured concentrations for a range of hazardous gases released from TR-driven combustion of cylindrical lithium iron phosphate (LFP) and pouch-style lithium cobalt oxide (LCO) LIB cells. Gas emissions were measured by dedicated analyzers and Fourier transform infrared spectroscopic (FTIR) analysis, and emission factors were calculated. Dangerous concentrations of hydrogen fluoride (HF) were observed, reaching up to 50 ppm from the combustion of single LIB cells. Large amounts of combustible electrolyte solvents and light hydrocarbons were released in some cases, depending on cell combustion behavior. Electrolyte solvents, hydrogen chloride (HCl), and particles were released earlier than other species and should be targeted for early TR detection. Gas emissions were correlated with cell state of charge (SOC) and combustion behavior. Cells at high SOCs had higher peak concentrations of HF, HCl, CO, and flammable hydrocarbons, and these peaks happened sooner after cell failure than for low-SOC tests. Full article
(This article belongs to the Special Issue Thermal Safety of Lithium Ion Batteries—2nd Edition)
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20 pages, 2329 KB  
Article
Multivariate Robustness Modeling of Cannabidiol and Δ9-Tetrahydrocannabinol Quantification Using Two-Level Full Factorial Design
by Athip Maha, Thanapat Songsak, Surang Leelawat and Chaowalit Monton
Sci. Pharm. 2026, 94(2), 42; https://doi.org/10.3390/scipharm94020042 - 20 May 2026
Viewed by 442
Abstract
The present study aimed to establish a robustness modeling framework for the determination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in cannabis extract using a multivariate approach. A two-level full factorial design was implemented to examine four critical analytical factors, including methanol [...] Read more.
The present study aimed to establish a robustness modeling framework for the determination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in cannabis extract using a multivariate approach. A two-level full factorial design was implemented to examine four critical analytical factors, including methanol concentration (80–85% v/v), flow rate (0.8–1.2 mL/min), column temperature (23–27 °C), and detection wavelength (208–212 nm). Seven analytical responses for each compound were assessed, including peak area, retention time, resolution, asymmetry factor, number of theoretical plates, capacity factor, and peak area difference relative to the reference method. Statistical analysis demonstrated that both main effects and interaction effects significantly influenced the measured responses. Design space construction was performed based on predefined acceptance criteria to ensure method robustness: resolution > 1.5, asymmetry < 1.5, number of theoretical plates > 2000, capacity factor > 2, and peak area difference within −5% to 5%. Predictive performance of the developed models was verified by comparing predicted and experimental results. Good agreement was observed under most conditions, whereas deviation was noted for THC quantification at a detection wavelength of 212 nm. Furthermore, CBD and THC contents determined under three selected operating conditions within the established design space were statistically comparable to those obtained using the reference method, except for the condition employing 212 nm detection. The Analytical GREEnness Metric Approach (AGREE) assessment indicated moderate greenness performance of the analytical procedure. Overall, the multivariate two-level full factorial design proved to be an effective tool for robustness modeling of the HPLC method for simultaneous quantification of CBD and THC. Full article
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30 pages, 4058 KB  
Article
Dimethyl Ether as a Compression Ignition Engine Fuel for Simultaneous NOx and PM Reduction
by Matthias Rollins, Juan Felipe Rodriguez, Bret C. Windom and Daniel B. Olsen
Energies 2026, 19(10), 2439; https://doi.org/10.3390/en19102439 - 19 May 2026
Viewed by 315
Abstract
Dimethyl ether (DME) is a promising alternative fuel for compression ignition (CI) engines due to its potential to simultaneously reduce nitrogen oxides (NOx) and particulate matter (PM) emissions while maintaining diesel-equivalent power. However, its combustion behavior under varying injection timing and [...] Read more.
Dimethyl ether (DME) is a promising alternative fuel for compression ignition (CI) engines due to its potential to simultaneously reduce nitrogen oxides (NOx) and particulate matter (PM) emissions while maintaining diesel-equivalent power. However, its combustion behavior under varying injection timing and exhaust gas recirculation (EGR) conditions remains insufficiently characterized for practical calibration. This study investigates the combustion, emissions, and performance of DME relative to diesel using a fully instrumented John Deere 6068CI550 single-cylinder research engine modified for high-pressure common-rail DME operation. Baseline tests were conducted at three ISO 8178 C1 steady-state modes with matched combustion phasing, load, and EGR to isolate fuel property effects. Injection timing and EGR sweeps were then performed at 1600 rpm and 50% load. Results show that DME produces 10–35% lower NOx and orders-of-magnitude lower PM than diesel while maintaining comparable thermal efficiency. DME exhibits a single-stage premixed heat release structure with reduced peak apparent heat release rates and 4–5° shorter combustion durations than diesel. Stable combustion was sustained up to 55% EGR, beyond which incomplete combustion increased carbon monoxide (CO), total hydrocarbons (THC), and fuel consumption. Optimal low-emission operation occurred near CA50 ≈ 16° ATDC and EGR levels of 30–40%. These findings demonstrate DME’s ability to mitigate the traditional diesel NOx–PM tradeoff and support its viability as a low-emission CI fuel. Full article
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18 pages, 1183 KB  
Article
The Impact of Planting Density and Vegetative Duration on Yield Optimization and Cannabinoid Stability in Medicinal Cannabis Under Controlled-Environment Cultivation
by Panagiotis Karnoutsos, Stratos Mallis, Eirini Sarrou, Nikos Koukovinos, Eleni Tsaliki, Marios Karagiovanidis, Ioannis Ganopoulos and Apostolos Kalivas
Horticulturae 2026, 12(5), 619; https://doi.org/10.3390/horticulturae12050619 - 17 May 2026
Viewed by 993
Abstract
Optimizing plant density and vegetative growth duration is important for improving productivity in controlled-environment medicinal cannabis cultivation. Although both factors strongly influence canopy development and yield, their combined effects under modern high-intensity LED lighting, and particularly their consequences for cannabinoid uniformity across the [...] Read more.
Optimizing plant density and vegetative growth duration is important for improving productivity in controlled-environment medicinal cannabis cultivation. Although both factors strongly influence canopy development and yield, their combined effects under modern high-intensity LED lighting, and particularly their consequences for cannabinoid uniformity across the canopy, remain insufficiently characterized. This study examined how planting density and vegetative duration influence plant growth, yield, and cannabinoid concentration in Cannabis sativa L. (strain ‘Fat Banana’) grown under controlled environment conditions, high-intensity LED lighting and precision fertigation. Two vegetative durations (10 and 28 days) were evaluated in separate but identical controlled-environment chambers under broad-spectrum high-intensity LED lighting and automated precision fertigation on rockwool substrate. The 10-day regime compared 8, 14 and 18 plants m−2; the 28-day regime compared 6, 8 and 10 plants m−2. Each combination was replicated across two independent cultivation cycles, and because density levels differed between regimes, direct between-regime comparisons were restricted to the shared density of 8 plants m−2. Extending the vegetative phase from 10 to 28 days increased plant height, stem diameter and internodal length. Area-based yield increased strongly with density, reaching 1091 g m−2 at 18 plants m−2 under the 10-day regime and 1009 g m−2 at 10 plants m−2 under the 28-day regime. Apical biomass exceeded basal biomass, but total THC concentration did not differ significantly among planting densities, vegetative durations or canopy positions. Higher planting densities combined with shorter vegetative periods can therefore increase area-based productivity while maintaining stable THC concentration under high-intensity LED cultivation. Full article
(This article belongs to the Section Protected Culture)
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27 pages, 1828 KB  
Article
Antitumor Activity of Cannabinoids and Their Interaction with Chemotherapy: A Systematic Review and Meta-Analysis of Preclinical Evidence
by Ioana Creangă-Murariu, Ioana-Irina Rezuș, Roshanak Karami, Amir Makolli, Codrin Chifu, Anett Rancz, Zoltán Sipos, Péter Ferdinandy, Renáta Papp, Brigitta Teutsch, Bogdan-Ionel Tamba, Péter Hegyi and Stefania Bunduc
Pharmaceuticals 2026, 19(5), 768; https://doi.org/10.3390/ph19050768 - 14 May 2026
Viewed by 1574
Abstract
Background: Cannabinoids are studied as anticancer agents, but their effects vary across tumors, compounds, and experimental settings, underscoring the need to define consistent patterns. Our objective was to map cannabinoid efficacy across cancer preclinical models and identify tumor settings with the greatest [...] Read more.
Background: Cannabinoids are studied as anticancer agents, but their effects vary across tumors, compounds, and experimental settings, underscoring the need to define consistent patterns. Our objective was to map cannabinoid efficacy across cancer preclinical models and identify tumor settings with the greatest translational promise. Methods: The protocol was registered on PROSPERO (CRD42025543744); PubMed, Embase, and CENTRAL were searched on 4 April 2024 for in vitro and in vivo studies assessing cannabinoid antitumor effects alone or with chemotherapy versus vehicle or chemotherapy only. Random-effects models yielded pooled mean differences (MD) with 95% confidence intervals (CI). MDs of viable cells were calculated for in vitro assays and tumor volume (mm3) for in vivo studies. Reports of various compounds, cannabidiol (CBD), tetrahydrocannabinol (THC) or synthetic cannabinoids, were pooled. Results: We included 189 studies in the final analysis. In vitro, cannabinoids reduced cell viability modestly overall, with significant effects in glioblastoma (MD −18.77 [CI: −27.15; −10.39]) and a nonsignificant trend in breast cancer (MD −6.75 [CI: −13.90; 0.40]). For in vivo, monotherapy showed the most consistent efficacy in glioblastoma, significantly reducing tumor volume by MD −980.58 mm3; [CI: −1270.2; −690.88]. Addition to temozolomide produced a favorable but nonsignificant decrease of MD −220.65 mm3; [CI: −579.34; 138.03, vs. temozolomide]. In breast cancer, cannabinoids achieved smaller yet significant tumor reductions (MD −402.64 mm3); [CI: −671.84; −133.45]. Synthetic agents had the largest effect (MD −1295.19 mm3); [CI: −1664.33; −928.05] -CBD plus doxorubicin vs. doxorubicin). Lung cancer (MD −562.17 mm3); [CI: −693.99; −430.35] and prostate cancer (MD −1136.59 mm3); [95% CI: −1320.97; −952.21] also had a significant response, whereas colon, pancreatic, and hepatocellular carcinoma models showed inconsistent or null responses. Conclusions: Cannabinoids show promise as adjuncts in oncotherapy, particularly in glioblastoma and breast cancer, to enhance chemotherapy efficacy. These findings should be interpreted with caution given the high inter-study heterogeneity typical of preclinical research and should be considered hypothesis-generating, warranting further validation in standardized and clinically relevant models. Full article
(This article belongs to the Section Pharmacology)
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