Framing planetary health: arguing for resource-centred science

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Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells

Cancer gene therapy requires the design of non-viral vectors that carry genetic material and selectively deliver it with minimal toxicity. Non-viral vectors based on cationic natural polymers can form electrostatic complexes with negatively-charged polynucleotides such as microRNAs (miRNAs). Here we investigated the physicochemical/biophysical properties of chitosan–hsa-miRNA-145 (CS–miRNA) nanocomplexes and the biological responses of MCF-7 breast cancer cells cultured in vitro. Self-assembled CS–miRNA nanocomplexes were produced with a range of (+/−) charge ratios (from 0.6 to 8) using chitosans with various degrees of acetylation and molecular weight. The Z-average particle diameter of the complexes was <200 nm. The surface charge increased with increasing amount of chitosan. We observed that chitosan induces the base-stacking of miRNA in a concentration dependent manner. Surface plasmon resonance spectroscopy shows that complexes formed by low degree of acetylation chitosans are highly stable, regardless of the molecular weight. We found no evidence that these complexes were cytotoxic towards MCF-7 cells. Furthermore, CS–miRNA nanocomplexes with degree of acetylation 12% and 29% were biologically active, showing successful downregulation of target mRNA expression in MCF-7 cells. Our data, therefore, shows that CS–miRNA complexes offer a promising non-viral platform for breast cancer gene therapy

External validation of a <em>red cell-based</em> blood prognostic score in patients with metastatic renal cell carcinoma treated with first-line immunotherapy combinations

\ua9 The Author(s) 2024. Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients’ counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). We performed a sub-analysis of a multicentre retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. Uni- and multivariable Cox regression models were used to assess the correlation between the red cell-based score and progression-free survival (PFS), and overall survival (OS). Logistic regression were used to estimate the correlation between the score and the objective response rate (ORR). The prognostic impact of the red cell-based score on PFS and OS was confirmed in the whole population regardless of the immunotherapy combination used [median PFS (mPFS): 17.4 vs 8.2 months, HR 0.66, 95% CI 0.47–0.94; median OS (mOS): 42.0 vs 17.3 months, HR 0.60, 95% CI 0.39–0.92; p &lt; 0.001 for both]. We validated the prognostic significance of the red cell-based score in patients with mRCC treated with first-line immunotherapy combinations. The score is easy to use in daily clinical practice and it might improve patient counselling

The neurochemistry of hypnotic suggestion

A diverse array of studies has been devoted to understanding the neurochemical systems supporting responsiveness to hypnotic suggestions, with implications for experimental and clinical applications of hypnosis. However, this body of research has only rarely been integrated and critically evaluated and the prospects for the reliable pharmacological manipulation of hypnotic suggestibility remain poorly understood. Here we draw on pharmacological, genotyping, neuroimaging, and electrophysiological research to synthesize current knowledge regarding the potential role of multiple widely-studied neurochemicals in response to suggestion. Although we reveal multiple limitations with this body of evidence, we identify converging results implicating different neurochemical systems in response to hypnotic suggestion. We conclude by assessing the extent to which different results align or diverge and outline multiple avenues for future research. Elucidating the neurochemical systems underlying response to suggestion has the potential to significantly advance our understanding of suggestion