Marcus Frank

Cannabinoids are potential anticancer agents for the add-on treatment of malignant tumors. Here, the effects of the previously less-explored non-psychoactive phytocannabinoids cannabigerol (CBG) and cannabichromene (CBC) on survival, apoptosis, and mitochondrial function were assessed in A549 and H460 lung cancer cells. CBG and CBC triggered concentration-dependent cell death, autophagy, and mitochondrial apoptosis in both cell lines, with apoptosis indicated by Annexin V staining, activation of caspase-8, -9, and -3/7, loss of mitochondrial membrane potential, and elevated cytosolic levels of mitochondrial cytochrome c. CBG also upregulated ATF4, a stress-responsive transcription factor involved in autophagy and apoptotic signaling, and enhanced PARP cleavage. Both cannabinoids increased mitochondrial superoxide formation and reduced the mitochondrial oxygen consumption rate, with CBG additionally decreasing NDUFB8, a subunit of respiratory chain complex I. Pharmacological receptor modulation showed that CBG- and CBC-induced cell death occurred independently of CB₁, CB₂, TRPV1, TRPM8, and PPARγ, whereas CBG-mediated cell death relied on PPARα, which also contributed to its apoptotic effects. In summary, CBG and CBC induce apoptosis and cell death in A549 and H460 cells, with PPARα mediating the effects of CBG, highlighting its potential as a therapeutic target.

Immune cell entry into the central nervous system (CNS) under neuroinflammatory conditions is commonly discussed in relation to established barrier interfaces, including the blood–brain barrier and the choroid plexus epithelium. In addition, an alternative anatomical route at the choroid plexus attachment region has been proposed, yet its structural organization remains poorly defined. Here, we provide a detailed descriptive analysis of the choroid plexus attachment region and identify glial structures reminiscent of a glia limitans. We analyzed the morphology of the choroid plexus attachment region in control mice using immunohistochemical and ultrastructural techniques. Immune cell accumulation under neuroinflammatory conditions was examined in the CupEAE mouse model, and human post-mortem sections were analyzed for comparative insights. Our results show that the murine choroid plexus attachment region contains an astrocytic accumulation in close proximity to a continuous basal lamina facing the choroid plexus stroma. Ultrastructural analyses indicate the presence of components associated with junctional complexes. In the CupEAE model, CD3-positive immune cells were more frequently observed in the choroid plexus base than in the brain parenchyma adjacent to the attachment region. In humans, choroid plexus attachment regions also exhibit astrocytic accumulation, though with a different basal lamina pattern. These results underline the complex organization of the choroid plexus attachment region. This anatomical description might be the basis for further studies to evaluate the relevance of the choroid plexus attachment region in immune cell migration to the brain parenchyma.

In the search for new therapeutic strategies for the treatment of skin cancer, cannabinoids have become the focus of scientific interest. The present study investigated the effects of the phytocannabinoids Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) on the viability, apoptosis, and mitochondrial function of human melanoma (A375) and cutaneous squamous cell carcinoma (SCC) cells (A431). Both cannabinoids caused a time- and concentration-dependent loss of viability and an upregulation of caspase-3/7 activity, associated with the induction of initiator caspases-8 and -9, PARP cleavage, and an increase in the autophagy marker LC3A/B-II. Inspired by the latest work on the dual role of heme oxygenase-1 (HO-1) in cell fate, the expression of this enzyme was examined and found to be upregulated at the mRNA and protein level by THC and CBD. Inhibition of HO-1 activity by tin protoporphyrin IX (SnPPIX) reduced the loss of viability caused by both cannabinoids, suggesting a cytotoxic rather than cytoprotective mediator role for this enzyme here. At the mitochondrial level, THC and CBD caused a reduction in membrane potential, a release of cytochrome c into the cytosol, and electron microscopically detectable mitochondrial damages. A more detailed functional analysis revealed an inhibition of mitochondrial oxygen consumption rate, accompanied by a decrease in various subunits of mitochondrial oxidative phosphorylation complexes. In conclusion, our data demonstrate a strong cytotoxic effect of THC and CBD on melanoma and cutaneous SCC cells involving mitochondrial apoptosis and mitochondrial dysfunction.

Objective: Anorexia nervosa (AN) is a severe eating disorder associated with extreme weight loss, hyperactivity, and amenorrhea. Neuroimaging studies revealed brain atrophy and disruption of white matter integrity in the corpus callosum (CC) of patients with AN. However, the underlying pathophysiological mechanisms remain unclear. Emerging evidence indicates that starvation induces changes in mitochondrial metabolism and dynamics. We hypothesize that disturbances in white matter integrity arise from modifications in oligodendrocytes, associated with changes in the morphology of myelinated fibers and mitochondrial structure. Method: The starvation‐induced hyperactivity (SIH) model was used, in which mice received a restricted daily amount of food in combination with free access to a running wheel. A body weight loss of 25% was maintained over 2 weeks, followed by a 3‐week refeeding phase. Oligodendrocyte density and staining intensity of oligodendrocyte lineage transcription factor 2 (OLIG2) in the CC were analyzed using immunohistochemical staining. Morphometric investigation of myelinated fibers and mitochondria was conducted by transmission electron microscopy (TEM) analysis. Results: Starvation led to decreased oligodendrocyte density and reduced anti‐OLIG2 staining intensity in the CC, which was reversible following refeeding. Additionally, starvation induced a decrease in axonal caliber and an increase in mitochondrial density in the white matter, accompanied by a reduction of mitochondrial area. Discussion: The findings suggest that oligodendroglial and axonal alterations, alongside disrupted mitochondrial dynamics, impair structural integrity in the white matter and contribute to the pathophysiology of AN.

Lepidopteran insects are among the most significant crop pests in the Americas, causing extensive economic damage to sugarcane, tobacco, cotton, tomato, and corn crops. To improve biopesticide design for their control, it is essential to characterize the insect cuticle, which acts as a barrier against fungal infections, regulates compound permeation, and affects bioproduct adhesion. This study characterized the cuticles of Diatraea saccharalis (Fabricius) (Lepidoptera: Crambidae) and Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) based on fatty acid composition, morphology, contact angle, adhesion and cohesion work, spreading coefficient, and surface free energy (polar and dispersive components). Diatraea saccharalis exhibited higher saturated fatty acid content, whereas H. zea showed greater polyunsaturated fatty acid levels. Morphologically, H. zea displayed more developed mandibles and ventral/dorsal spines compared with D. saccharalis . Water had the highest adhesion work on D. saccharalis , whereas formamide liquid showed the highest adhesion on H. zea . Dimethyl sulfoxide and ethylene glycol spread more effectively on both species. Overall, D. saccharalis exhibited hydrophilic cuticle properties, whereas H. zea was more hydrophobic. This study provides foundational insights into cuticular characteristics, enabling the development of biopesticides with improved efficacy for pest control in agricultural systems.

Two specimens of Mobula thurstoni (Lloyd, 1908) were obtained from fishermen of Karangasem, Indonesia, and studied for trypanorhynch cestodes. Archaenybelina gen. nov., including two new species A. pseudotetrabothrialis sp. nov. and A. mimicricestus sp. nov., were recorded from the stomach and spiral valve and analysed for details of scolex and segment morphology, and surface ultrastructure. The new genus is characterized by 4 asymmetrical bothria separated by deep posterior notches, the presence of tegumental grooves, a homeoacanthous heteromorphous armature and a unique segment morphology. Both species can be separated by different hook sizes, basal hook rows and distribution of bothrial microtriches. Scolex surface ultrastructure shows hamulate spinitriches on bothria, lineate spinitriches along bothrial margins, and papilliform filitriches on the scolex peduncle. Similar microtriches have been reported from the bothrial margins of the Tentaculariidae. Tegumental grooves with a probably secretory function based on histology are present on the posterior bothrial margin. A collar of uncinate microtriches appear at the outer surface, separated from an internal bulbous structure, clearly distinguish this organ from the ciliated pits of the Otobothriidae. Based on four bothria, appearing not entirely separated at the anterior part of the scolex that indicates an originally bifossate state, a homeoacanthous heteromorphous armature, tegumental grooves, the absence of prebulbar organs and the presence of muscular rings, we assign the new genus into the Paranybeliniidae Schmidt, 1970. Describing first details of the segment morphology add to the family diagnosis in the most recent classification. The unique morphology of the new genus including its potential life cycle that involves oceanic devil rays as final and euphausiid crustaceans as second intermediate hosts are discussed.

The basis of circular economy is the use and valorization of renewable raw materials. Especially in developing countries, crop waste such as straw and rice straw have high potential for further utilization. Within this report, we present a holistic strategy including the selective isolation of cellulose via simple, environmental benign two-step process. Rice straw was easily dissolved in a non-derivatizing electrolyte solvent such as aqueous solution of tetrabutylphosphonium hydroxide (TBPH) (50 wt%) at room temperature followed by precipitation in water. Quantitative amount of raw cellulose was recovered within a short period of time without heating or cooling enabling a further application of biomass material. The structure and characterization of the raw cellulose were investigated by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and by scanning (SEM) and transmission electron microscopy (TEM). This method could be an excellent alternative to the current extraction methods such as the KRAFT process. Indeed, the same chemicals as for the isolation can be used to prepare regenerated cellulose film of high purity with the raw cellulose. Due to its sustainability and exceptional biodegradability, these films have a great potential for applications in environment, textile, and separation industry. No modification of the cellulose during the extraction and preparation process occurs thus, these films are no plastics and thus can be used without regulations. In general, a full “circular economy” process is provided: valuable raw materials (cellulose) are recovered selectively from natural resources such as rice straw and further to enable products with high applicability in life (cellulose packaging film). The cradle-to-cradle process is closed by fast biodegradation of the used products.

The additive manufacturing of titanium–niobium–tantalum alloys with nominal chemical compositions Ti–xNb–6Ta (x = 20, 27, 35) by means of laser beam powder bed fusion is reported, and their potential as implant materials is elaborated by mechanical and biological characterization. The properties of dense specimens manufactured in different build orientations and of open porous Ti–20Nb–6Ta specimens are evaluated. Compression tests indicate that strength and elasticity are influenced by the chemical composition and build orientation. The minimum elasticity is always observed in the 90° orientation. It is lowest for Ti–20Nb–6Ta (43.2 ± 2.7 GPa) and can be further reduced to 8.1 ± 1.0 GPa for open porous specimens (p < 0.001). Furthermore, human osteoblasts are cultivated for 7 and 14 days on as-printed specimens and their biological response is compared to that of Ti–6Al–4V. Build orientation and cultivation time significantly affect the gene expression profile of osteogenic differentiation markers. Incomplete cell spreading is observed in specimens manufactured in 0° build orientation, whereas widely stretched cells are observed in 90° build orientation, i.e., parallel to the build direction. Compared to Ti–6Al–4V, Ti–Nb–Ta specimens promote improved osteogenesis and reduce the induction of inflammation. Accordingly, Ti–xNb–6Ta alloys have favorable mechanical and biological properties with great potential for application in orthopedic implants.

To improve the wear resistance of articulating metallic joint endoprostheses, the surfaces can be coated with titanium niobium nitride (TiNbN). Under poor tribological conditions or malalignment, wear can occur on these implant surfaces in situ. This study investigated the biological response of human osteoblasts to wear particles generated from TiNbN‐coated hip implants. Abrasive particles were generated in a hip simulator according to ISO 14242‐1/−2 and extracted with Proteinase K. Particle characteristics were evaluated by electron microscopy and energy dispersive x‐ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP‐MS) and dynamic light scattering (DLS) measurements. Human osteoblasts were exposed to different particle dilutions (1:20, 1:50, and 1:100), and cell viability and gene expression levels of osteogenic markers and inflammatory mediators were analyzed after 4 and 7 days. Using ICP‐MS, EDS, and DLS measurements, ~70% of the particles were identified as TiNbN, ranging from 39 to 94 nm. The particles exhibited a flat and subangular morphology. Exposure to particles did not influence cell viability and osteoblastic differentiation capacity. Protein levels of collagen type 1, osteoprotegerin, and receptor activator of nuclear factor κB ligand were almost unaffected. Moreover, the pro‐inflammatory response via interleukins 6 and 8 was minor induced after particle contact. A high number of TiNbN wear particles only slightly affected osteoblasts' differentiation ability and inflammatory response compared to metallic particles. Nevertheless, further studies should investigate the role of these particles in peri‐implant bone tissue, especially concerning other cell types.