Search Results (1,099)

Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ⁹-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion. Full article

The commercialization of proton-conducting fuel cells (PCFCs) is hindered by the limited electroactivity and durability of cathodes at intermediate temperatures ranging from 400 to 700 °C, a challenge exacerbated by an insufficient understanding of high-entropy perovskite (HEP) materials for oxygen reduction reaction (ORR) optimization. This study introduces an yttrium-doped HEP to address these limitations. A comparative analysis of Ce_0.2−xY_xBa_0.2Sr_0.2La_0.2Ca_0.2CoO_3−δ (x = 0, 0.2; designated as CBSLCC and YBSLCC) revealed that yttrium doping enhanced the ORR activity, reduced the thermal expansion coefficient (19.9 × 10⁻⁶ K⁻¹, 30–900 °C), and improved the thermomechanical compatibility with the BaZr_0.1Ce_0.7Y_0.1Yb_0.1O_3−δ electrolytes. Electrochemical testing demonstrated a peak power density equal to 586 mW cm⁻² at 700 °C, with a polarization resistance equaling 0.3 Ω cm². Yttrium-induced lattice distortion promotes proton adsorption while suppressing detrimental Co spin-state transitions. These findings advance the development of durable, high-efficiency PCFC cathodes, offering immediate applications in clean energy systems, particularly for distributed power generation. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Recently, we have described SrMo_1-xMg_xO_3-δ perovskites (x = 0.1, 0.2) as excellent anode materials for solid oxide fuel cells (SOFCs), with mixed ionic and electronic conduction (MIEC) properties. After depositing on the solid electrolyte, they were annealed for sintering at high temperatures (typically 1000 °C), giving rise to oxidized scheelite-type phases, with SrMo_1-xMg_xO_4-δ (x = 0.1, 0.2) stoichiometry. To obtain the active perovskite phases, they were reduced again in the working anode conditions, under H₂ atmosphere. Therefore, there must be an excellent reversibility between the oxidized Sr(Mo, Mg)O_4-δ scheelite and the reduced Sr(Mo, Mg)O_3-δ perovskite phases. This work describes the topotactical oxidation, by annealing at 400 °C in air, of the SrMo_0.9Mg_0.1O_3-δ perovskite oxide. The characterization by X-ray diffraction (XRD) and neutron powder diffraction (NPD) was carried out in order to determine the crystal structure features. The scheelite oxides are tetragonal, space group I4₁/a (No. 88), whereas the perovskites are cubic, s.g. Pm-3m (No. 221). The Rietveld refinement of the scheelite phase from NPD data after annealing the perovskite at 400 °C and cooling it down slowly to RT evidences the absence of intermediate phases between perovskite and scheelite oxides, as well as the presence of oxygen vacancies in both oxidized and reduced phases, essential for their performance as MIEC oxides. The topotactical relationship between both crystal structures is discussed. Full article

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines. Full article

The gel-forming ability of collagens is vital for their application in cell scaffolds, yet very few comparative studies on fish collagen sources are available. This study isolated and characterized type I collagens from carp skin (CSK), scales (CSC), and swim bladders (CSB) and sturgeon skin (SSK) and swim bladders (SSB). The carp collagens exhibited higher thermal stability (34.75–34.78 °C) and formed more transparent, stronger gels than the sturgeon collagens. Additionally, as demonstrated by scanning electron microscopy, the sturgeon collagens exhibited faster fibril formation, with visible fibrils after 3 h which grew thicker but did not form bundles. The carp collagens, in contrast, initially displayed fewer, thinner, and longer fibrils, with their formation accelerating over time and fibril bundles emerging after 24 h. All collagen solutions of 4% (w/v) exhibited shear-thinning flow behavior, with the carp-derived solutions showing higher viscosities (10³–10⁴ Pa·s) than those demonstrated by the sturgeon-derived solutions (10²–10³ Pa·s). The CSBs and SSBs demonstrated the highest storage (G′) and loss (G″) moduli, with the former exhibiting the lowest loss tangent (tan δ), indicative of a stronger gel structure. The gels at 24 h showed slightly poorer mechanical properties than those at 3 h. The CSC and SSB gels had the highest thermal stability. These findings highlight the distinctiveness of the characteristics of collagens and their gels, emphasizing their potential in biomaterial applications. The present study also provides a foundational framework for assessing cellular responses in a comparative context that may help in identifying the most suitable collagen types for biomedical applications. Full article

The structural and electrical properties of double perovskite compounds SrLaFe_1−xMn_xTiO_6−δ (x = 0, 0.33, 0.67, and 1.0) were studied using X-ray diffraction (XRD) and dielectric impedance measurements. The reparation of perovskite compounds was successfully achieved through the precursor solid-state reaction in air at 1250 °C. The purity phase and crystal structures of perovskite compounds were determined by means of the standard Rietveld refinement method using the FullProf suite. The best fitting results showed that SrLaFeTiO_6−δ was orthorhombic with space group Pnma, and both SrLaFe_0.67Mn_0.33TiO_6−δ and SrLaFe_0.33Mn_0.67TiO_6−δ were cubic structures with space group Fm3m, while SrLaMnTiO_6−δ was tetragonal with a I/4m space group. The charge density maps obtained for these structures indicated that the compounds show an ionic and mixed ionic–electronic conduction. The dielectric impedance measurements were carried out in the range of 20 Hz to 1 MHz, and the analysis showed that there is more than one relaxation mechanism of Debye type. Doping with Mn was found to reduce the dielectric impedance of the samples, and the major contribution to the dielectric impedance was established to change from a capacitive for SrLaFeTiO_6−δ to a resistive for SrLaMnTiO_6−δ. The fall in values of electrical resistance may be related to the possible occurrence of the double exchange (DEX) mechanism among the Mn ions, provided there is oxygen deficiency in the samples. DC-resistivity measurements revealed that SrLaFeTiO_6−δ was an insulator while SrLaMnTiO_6−δ was showing a semiconductor–metallic transition at ~250 K, which is in support of the DEX interaction. The dielectric impedance of SrLaFe_0.67Mn_0.33TiO_6−δ was found to be similar to that of (La,Sr)(Co,Fe)O_3-δ, the mixed ionic–electronic conductor (MIEC) model. The occurrence of a mixed ionic–electronic state in these compounds may qualify them to be used in free lead solar cells and energy storage technology. Full article

Complex antimony pyrochlores Bi_2.7M_0.46Ni_0.70Sb₂O_10+Δ (M = Zn, Mg) were synthesized from oxide precursors, using the solid-state reaction method. For each composition variant, the pyrochlore phase formation process was studied during solid-state synthesis in the range of 500–1050 °C. The influence of zinc and magnesium on the phase formation process was established. The interaction of oxide precursors occurs at a temperature of 600 °C and higher, resulting in the formation of bismuth stibate (Bi₃SbO₇) as a binary impurity phase. Oxide precursors, including bismuth(III) and antimony(III,V) oxides, are fixed in the samples up to 750 °C, at which point the intermediate cubic phase Bi₃M_2/3Sb_7/3O₁₁ (sp. gr. Pn-3, M = Zn, Ni) is formed in the zinc system. Interacting with transition element oxides, it is transformed into pyrochlore. An intermediate phase with the Bi_4.66Ca_1.09VO_10.5 structure (sp. gr. Pnnm) was found in the magnesium system. The unit cell parameter of pyrochlore for two samples has a minimum value at 800 °C, which is associated with the onset of high-temperature synthesis of pyrochlore. The synthesis of phase-pure pyrochlores is confirmed by high-resolution Raman spectroscopy. The data interpretation showed that the cations in Ni/Zn pyrochlore are more likely to be incorporated into bismuth positions than in Ni/Mg pyrochlore. The nickel–magnesium pyrochlore is characterized by a low-porosity microstructure, with grain sizes of up to 3 μm, according to SEM data. Zinc oxide has a sintering effect on ceramics. Therefore, the grain size in ceramics is large and varies from 2 to 7 μm. Full article

Cannabis sativa is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases. Previous research showed that cannabinol (CBN), a minor cannabinoid derived from Δ⁹-tetrahydrocannabinol, exhibits antioxidant, anti-inflammatory, analgesic, and anti-bacterial effects. The objective of this study was to assess the protective potential of 24 h CBN pre-treatment, applied at different concentrations (5 µM, 10 µM, 20 µM, 50 µM, and 100 µM), in differentiated neuroblastoma × spinal cord (NSC-34) cells. Transcriptomic analysis was performed using next-generation sequencing techniques. Our results reveal that CBN had no negative impact on cell viability at the tested concentrations. Instead, it showed a significant effect on stress response and neuroplasticity-related processes. Specifically, based on the Reactome database, the biological pathways mainly perturbed by CBN pre-treatment were investigated. This analysis highlighted a significant enrichment in the Reactome pathway’s cellular response to stress, cellular response to stimuli, and axon guidance. Overall, our results suggest that CBN holds promise as an adjuvant agent for neurodegenerative diseases by modulating genes involved in neuronal cell survival and axon guidance. Full article

Electrochemical devices on solid electrolytes are closely considered from the point of view of efficient utilization of environmental resources in order to obtain a variety of products, including those with high added cost. This study provides insight into the functionality of electrochemical cells that have been designed with a specific configuration. These cells have the same ionic composition of the anode, cathode, and electrolyte. This was achieved by iron doping of highly conductive (La,Sr)(Ga,Mg)O_3−δ electrolyte, and gallium and magnesium doping of the electrode material based on (La,Sr)FeO_3−δ. The main focus in this study is on the electrochemical behavior of such cells depending on the oxygen partial pressure in the gas phase, as well as the stability of the electrochemical performance over time for more than 950 h of testing. According to the obtained results, the electrochemical cell with a completely identical ionic composition of electrodes La_0.6Sr_0.4Fe_0.85Ga_0.1Mg_0.05O_3−δ and electrolyte (La_0.8Sr_0.2)_0.98Ga_0.7Fe_0.1Mg_0.2O_3−δ demonstrated the best set of optimal performances. This consists of excellent chemical compatibility, high electrochemical activity (0.08 Ω cm² in air at 800 °C), and a minor degradation rate. Full article

Cobalt-based perovskite oxides exhibit remarkable catalytic activity owing to abundant oxygen vacancies and mixed ionic–electronic conductivity, but they suffer from structural instability. In contrast, iron-based perovskite oxides are thermochemically stable under oxidizing and reducing conditions but are catalytically limited. To combine these complementary properties, a composite perovskite oxide was designed and prepared by infiltrating Sr_0.95Ce_0.05CoO_3−δ (SCC) into Ba_0.5Sr_0.5Fe_0.8Cu_0.2O_3−δ (BSFC). The SCC precursor solution was dropwise applied to a BSFC|SDC|BSFC symmetric cell and heat treated. Surface morphology and compositional analyses confirmed the distribution of SCC nanoparticles on the BSFC surface. High-temperature X-ray diffraction and Rietveld refinement results revealed that both BSFC and SCC retained the cubic perovskite structure (space group Pm-3m) at room temperature. No phase transition or secondary phase formation was observed during heating from 200 to 800 °C, and the peak shifts are attributed to thermal expansion and possible oxygen loss at elevated temperatures. Upon cooling, the diffraction patterns returned to their initial state, confirming a high-temperature structural stability. XPS analysis showed an increase in the satellite peak intensity associated with Fe³⁺ after SCC infiltration, and the average oxidation state of Fe decreased from 3.52 (BSFC) to 3.49 (composite perovskite oxide). The O 1s spectra revealed a higher relative content of surface-adsorbed oxygen species in the composite, indicating increased oxygen vacancy formation. Full article

Chondrocytes maintain cartilage integrity through coordinated regulation of extracellular matrix (ECM) synthesis and remodeling. These processes depend on ECM dynamic interactions, mediated by integrin-based focal adhesions and associated cytoskeletal components. While the roles of core adhesion proteins are well described, the involvement of sarcoglycans (SGs) remains unclear in chondrocytes. Drawing parallels from striated muscle, where the SG subcomplex stabilizes the sarcolemma, we hypothesized that SGs similarly integrate into chondrocyte adhesion complexes. This study investigated the SGs (α, β, γ, δ) expression with cytoskeletal and adhesion proteins, including actin and vinculin, in human chondrocytes cultured by immunofluorescence, qPCR, and siRNA-mediated silencing. All four SG isoforms were expressed in the cytoplasmic and membrane domains, with enrichment at focal adhesion sites. Double labeling revealed SG colocalization with F-actin stress fibers and vinculin, indicating integration into the core adhesion complex. Silencing of each SG resulted in disrupted actin stress fibers, diffuse vinculin distribution, reduced focal plaque number, and a change in cell morphology. These findings support the hypothesis that SGs regulate actin cytoskeletal dynamics and focal contact stabilization. Loss of SG function compromises chondrocyte shape and adhesion, highlighting the importance of these glycoproteins also in non-muscle cells. Full article

T cells equipped with chimeric antigen receptors (CARs) have evolved into an essential pillar of lymphoma therapy, reaching second-line treatment. In solid cancers, however, a dearth of lasting CAR T cell activation poses the major obstacle to achieving a substantial and durable anti-tumor response. To extend T cell cytotoxic capacities, we engineered CAR T cells to constitutively release an immunostimulatory variant of soluble SLAMF6. While wild-type SLAMF6 induces T cell exhaustion, CAR T cells with the soluble Δ17-65 SLAMF6 variant exhibited refined, CAR redirected functionality compared to canonical CAR T cells. CD28-ζ CAR T cells releasing soluble SLAMF6 increased IFN-γ secretion and augmented CD25 upregulation on CD4⁺ CAR T cells upon CAR engagement by pancreatic carcinoma and melanoma cells. Moreover, under conditions of repetitive antigen encounter, SLAMF6-secreting CAR T cells evinced superior cytotoxic capacity in the long term. Mechanistically, SLAMF6-secreting CAR T cells showed predominantly a central memory phenotype, a PD-1^- TIGIT^- double negative profile, and reduced expression of exhaustion-related transcription factors IRF-4 and TOX with augmented amplification and persistence capacities. Overall, CAR T cells engineered with the release isoform 2 SLAMF6 establish an auto-stimulatory loop with the potential to boost the cytolytic attack against solid tumors. Full article

Recent evidence suggests a high-sodium microenvironment in breast tumors. However, the exact role of this high-sodium microenvironment on tumorigenesis is unknown. Salt (sodium chloride, NaCl) is a well-known inflammatory molecule playing a significant role in various chronic ailments like cardiovascular and autoimmune diseases. Importantly, chronic inflammation is recognized as one of the major hallmarks of carcinogenesis. Breast cancer cell culture-based studies demonstrated that high-salt (HS) treatment (Δ35–50 mM NaCl) induced cancer cell proliferation. However, preclinical murine research showed reduced tumor progression kinetics in mice fed a short-term HS diet (4% NaCl diet, 0–2 weeks prior to the injection of tumor cells). Molecular studies demonstrated that the short-term HS diet induced the inflammatory activation of naïve CD4+ T cells to the Th17/Th1 anti-tumor phenotype. As human health-related adverse outcomes from HS diets usually occur as a consequence of prolonged HS intake over a period of several years, we have developed a novel chronic HS dietary murine tumor model. In this model, tumor cells are sequentially passaged (four cycles) in vivo under high-salt conditions, and tumor kinetics were analyzed in the passage-4 mice. These studies demonstrated enhanced tumor progression (pro-tumor) under chronic HS dietary conditions through the activation of tumor-initiating stem cells, along with the exhaustion of immune cells. Based on the, apparently paradoxical, evidence, we propose a comprehensive unifying hypothesis to elucidate the complex role of a high-sodium microenvironment towards tumor immune sculpting. This understanding will enable novel drug repositioning strategies, the development of unique ion channel-based anti-cancer therapeutics and promote low-salt diet intake in breast cancer patients on immunotherapy. Full article

Delta-9-tetrahydrocannabinol (Δ-9-THC or THC), the primary psychoactive constituent of cannabis, can lead to adverse health conditions, including mental health issues, brain impairment, and cardiac and respiratory problems. The amount of THC in cannabis has steadily climbed over the past few decades, with today’s cannabis having three times the concentration of THC compared to 25 years ago. Inhalation is a major route of exposure, allowing substances to enter the body via the respiratory tract. THC exposure causes cell death in the airway epithelium; however, the molecular underpinning of THC exposure-induced bronchial epithelial cell death is not clearly understood. To address the mechanisms involved in this process, the present study examined the cell viability, oxidative stress, lipid peroxidation, and transcriptional alterations caused by various concentrations of Δ-9-THC (0, 800, 1000, 1200, and 1500 ng/mL) in a human bronchial epithelial cell line (BEAS-2B) in vitro. Δ-9-THC exposure caused a significant dose-dependent decrease in cell viability after 24 h exposure. Transcriptome analysis showed a distinct dose-dependent response. HIF-1 signaling, ferroptosis, AMPK signaling, and immunogenic pathways were activated by Δ-9-THC-upregulated genes. Glutathione and fatty acid metabolic pathways were significantly altered by Δ-9-THC-dependent downregulated genes. Ingenuity Pathway Analysis (IPA) revealed several top canonical pathways altered by Δ-9-THC exposure, including ferroptosis, NRF-2-mediated oxidative stress response, caveolar-mediated endocytosis (loss of cell adhesion to the substrate), tumor microenvironment, HIF1alpha signaling, and the unfolded protein response pathway. Δ-9-THC-induced cell death was ameliorated by inhibiting the ferroptosis pathway, whereas treatments with ferroptosis agonist exacerbated the cell death process, suggesting that Δ-9-THC-induced bronchial epithelial cell death potentially involves the ferroptosis pathway. Full article