Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis.

Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the development of itch and the acute-to-chronic itch transition remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of inflammatory cytokines, activity-induced genes, and markers of neuropathic itch. Finally, we demonstrate that neutrophils are required for induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory neurons, and we find that that CXCR3 antagonism attenuates chronic itch

Montivipera bornmuelleri Venom: Inhibitory Effect on Staphylococcus epidermidis and Escherichia coli F1F0-ATPases and Cytotoxicity on HCT116 Cancer Cell Lines

International audienceIn this work, we pursued the biological characterization of the venom of Montivipera bornmuelleri, a viper from the Lebanese mountains. In relation to its antibacterial potential, the inhibitory effect of this venom on the F1F0-ATPase enzymes of Gram-positive Staphylocoocus epidermidis and Gram-negative Escherichia coli bacteria was examined. In order to determine the degree of cytotoxicity of the venom on the HCT116 human colon cancer cell lines, the biological MTT proliferation and cell viability test were implemented. After validation of the enzymatic F1F0-ATPase model by the spectrophotometric method, using quercetin as the reference ligand, results revealed that M. bornmuelleri venom is able to inhibit the activity of the enzyme of these two bacteria with a concentration of the order of 100–150 µg/mL. In addition, a venom concentration of 10 µg/mL was sufficient to kill the totality of HCT116 cell lines cultivated in vitro. These data show that M. bornmuelleri venom is a mixture of diverse molecules presenting activities of interest, and is a potential source to explore in order to discover new drug candidates

The Cytotoxic Effect of Apis mellifera Venom with a Synergistic Potential of Its Two Main Components—Melittin and PLA2—On Colon Cancer HCT116 Cell Lines

International audienceColon carcinogenesis is ranked second globally among human diseases after cardiovascular failures. Bee venom (BV) has been shown to possess in vitro anticancer effects against several types of cancer cells. The two main biopeptides of Apis mellifera BV, namely, melittin (MEL) and phospholipase A2 (PLA2), are suspected to be the biomolecules responsible for the anticancer activity. The present work aims to evaluate the cytotoxic effect of the A. mellifera venom on human colon carcinoma cells (HCT116), and to assess the synergistic effect of MEL and PLA2 on these cells. After analyzing, through high-pressure liquid chromatography, the proportions of MEL and PLA2 on BV, we have established a cell viability assay to evaluate the effect of BV, MEL, PLA2, and a mixture of MEL and PLA2 on the HCT116 cells. Results obtained showed a strong cytotoxicity effect induced by the A. mellifera venom and to a lower extent MEL or PLA2 alone. Remarkably, when MEL and PLA2 were added together, their cytotoxic effect was greatly improved, suggesting a synergistic activity on HCT116 cells. These findings confirm the cytotoxic effect of the A. mellifera venom and highlight the presence of synergistic potential activities between MEL and PLA2, possibly inducing membrane disruption of HCT116 cancer cells. Altogether, these results could serve as a basis for the development of new anticancer treatments

Functional magnetic resonance imaging (fMRI) as adjunct for planning laser interstitial thermal therapy (LITT) near eloquent structures.

LITT is a minimally-invasive laser ablation technique used to treat a wide variety of intracranial lesions. Difficulties performing intraoperative mapping have limited its adoption for lesions in/near eloquent regions. In this institutional case series, we demonstrate the utility of fMRI-adjunct planning for LITT near language or motor areas. Six out of 7 patients proceeded with LITT after fMRI-based tractography determined adequate safety margins for ablation. All underwent successful ablation without new or worsening postoperative symptoms requiring adjuvant corticosteroids, including those with preexisting deficits. fMRI is an easily accessible adjunct which may potentially reduce chances of complications in LITT near eloquent structures

The Lebanese Red Algae Jania rubens: Promising Biomolecules against Colon Cancer Cells

International audienceColorectal cancer (CRC) is ranked the second most lethal type of tumor globally. Thus, developing novel anti-cancer therapeutics that are less aggressive and more potent is needed. Recently, natural bioactive molecules are gaining interest as complementary and supportive antineoplastic treatments due to their safety, effectiveness, and low cost. Jania rubens (J. rubens) is a red coral seaweed abundant in the Mediterranean and bears a significant pharmacological essence. Despite its therapeutic potential, the natural biomolecules extracted from this alga are poorly identified. In this study, the proximal analysis revealed high levels of total ash content (66%), 11.3% proteins, 14.5% carbohydrates, and only 4.5% lipids. The elemental identification showed magnesium and calcium were high among its macro minerals, (24 ± 0.5 mg/g) and (33 ± 0.5 mg/g), respectively. The Chlorophyll of J. rubens was dominated by other pigments with (0.82 ± 0.02 mg/g). A 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay identified effective antioxidant activity in various J. rubens extracts. More importantly, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium reduction and wound healing assays indicate that organic extracts from J. rubens significantly counteract the proliferation of colon cancer cell lines (HCT-116 and HT-29) and inhibit their migratory and metastatic properties in a dose and time-dependent manner. Overall, this study provides insight into the physicochemical properties of red seaweed, J. rubens, and identifies its significant antioxidant, cytotoxic, and anti-migratory potential on two colorectal cell lines, HCT-116 and HT-29

sj-docx-1-tan-10.1177_17562864231202064 – Supplemental material for Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study

Supplemental material, sj-docx-1-tan-10.1177_17562864231202064 for Structural connections of the centromedian nucleus of thalamus and their relevance for neuromodulation in generalized drug-resistant epilepsy: insight from a tractography study by Luigi G. Remore, Ziad Rifi, Hiroki Nariai, Dawn S. Eliashiv, Aria Fallah, Benjamin D. Edmonds, Joyce H. Matsumoto, Noriko Salamon, Meskerem Tolossa, Wexin Wei, Marco Locatelli, Evangelia C. Tsolaki and Ausaf A. Bari in Therapeutic Advances in Neurological Disorders</p