Revealing hidden knowledge in amnestic mice.

Alzheimer's disease (AD) is a form of dementia in which memory and cognitive decline is thought to arise from underlying neurodegeneration. These cognitive impairments, however, are transient when they first appear and can fluctuate across disease progression. Here, we investigate the neural mechanisms underlying fluctuations of performance in amnestic mice.

Repurposing FDA-approved drugs to target G-quadruplexes in breast cancer.

Breast cancer, a leading cause of cancer-related mortality in women, is characterized by genomic instability and aberrant gene expression, often influenced by noncanonical nucleic acid structures such as G-quadruplexes (G4s). These structures, commonly found in the promoter regions and 5'-untranslated RNA sequences of several oncogenes, play crucial roles in regulating transcription and translation. Stabilizing these G4 structures offers a promising therapeutic strategy for targeting key oncogenic pathways.

Kanamycin and G-Quadruplexes: An Exploration of Binding Interactions.

G-quadruplexes (G4s) are distinctive four-stranded nucleic acid structures formed by guanine-rich sequences, making them attractive targets for drug repurposing efforts. Modulating their stability and function holds promise for treating diseases like cancer. To identify potential drug candidates capable of interacting with these complex DNA formations, docking studies and molecular dynamics (MDs) simulations were conducted.

Expanding the Functions of KHSRP Protein: Insights into DNA G-Quadruplex Binding.

KHSRP (KH-type splicing regulatory protein) is a multifunctional nucleic acid-binding protein that regulates various cellular processes, with critical roles in controlling gene expression. G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in essential cellular activities, including gene expression, and are recognized as potential therapeutic targets in cancer. The biological functions of G4s are mediated by proteins making their formation highly dynamic within cells.

Design, Synthesis, and Anticancer Activity of Drug-like Iron Chelators/G-Quadruplex Binders as Synergic Dual Targeting Agents.

Iron homeostasis is strictly related to numerous physiological pathways including cell cycle progression and cell growth. The newest anticancer strategies focus on either depleting the cells with a suitable chelator or increasing their loading by administering iron complexes to induce ferroptosis. Iron depletion inhibits cell proliferation, while iron overload induces the damage of guanine nucleobases in G-quadruplex structures via ROS generation, leading to genome instability.

Screening of native wild Salvia nemorosa populations for chemical compositions, antioxidant activity and UHPLC-HRMS profiling.

In this study, screening of the collected 70 Salvia nemorosa L. populations from 54 habitats from West Azerbaijan province, Iran was evaluated by analyzing the content of phytochemical compounds, antioxidant activity, and UHPLC-HRMS profiling in different populations. The aerial parts of the plants were analyzed based on total phenolic (TPC) and flavonoid (TFC), total tannin (TTC), ascorbic acid (AAC), chlorophylls (Cla, and Clb), total carotenoid (TCC), β-carotene, antioxidant activity (by DPPH and FRAP assays), and 40 polyphenolic compounds by UHPLC-HRMS (phenolic acids, flavonoids and fatty acyl glicosides).

Pursuing Polypharmacology: Benzothiopyranoindoles as G-Quadruplex Stabilizers and Topoisomerase I Inhibitors for Effective Anticancer Strategies.

Here, we explored the benzothiopyranoindole scaffold to develop antiproliferative agents with a polypharmacological profile targeting both G-quadruplex (G4)-structures and Topoisomerase (Topo) I enzyme. In a preliminary optimization phase, compound was selected from an in-house collection as a suitable lead for the rational development of a small library of analogs (-). When assayed in NIH's NCI-60 Human Cancer Cell Line In Vitro Screen Program, compound and its demethylated analogue showed significant antiproliferative/cytotoxic activity.

Sensitization of melanoma cells to standard chemotherapy: G-quadruplex binders as synergistic agents.

The use of chemotherapeutics has achieved considerable success in cancer therapy; however, their toxicity can severely impact patients' health. In this study, aiming to reduce the doses and potential side effects of traditional chemotherapeutics, we systematically treated A375MM human melanoma cells with seven clinically approved antineoplastic drugs, in combination with three well-characterized G-quadruplex (G4) ligands, using either simultaneous or sequential dosing schedules. Interestingly, the G4 binders synergized with most of the investigated anticancer drugs, with the degree of synergism being strictly dependent on both the treatment schedule and the drug sequence employed.

The Efficacy of Ketogenic Diets (Low Carbohydrate; High Fat) as a Potential Nutritional Intervention for Lipedema: A Systematic Review and Meta-Analysis.

Background: Lipedema is a frequently misdiagnosed condition in women, often mistaken for obesity, which significantly deteriorates both quality of life and physical health. Recognizing the necessity for holistic treatment strategies, research has increasingly supported the integration of specific dietary approaches, particularly ketogenic diets focusing on low-carbohydrate and high-fat intake.

Objectives: to evaluate the impact of ketogenic diets on women with lipedema through a systematic review and meta-analysis.

Discovering Dually Active Anti-cancer Compounds with a Hybrid AI-structure-based Approach.

Cancer's persistent growth often relies on its ability to maintain telomere length and tolerate the accumulation of DNA damage. This study explores a computational approach to identify compounds that can simultaneously target both G-quadruplex (G4) structures and poly(ADP-ribose) polymerase (PARP)1 enzyme, offering a potential multipronged attack on cancer cells. We employed a hybrid virtual screening (VS) protocol, combining the power of machine learning with traditional structure-based methods.

An unbiased lncRNA dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for multiple myeloma.

Multiple myeloma (MM) is an incurable malignancy characterized by altered expression of coding and noncoding genes promoting tumor growth and drug resistance. Although the crucial role of long noncoding RNAs (lncRNAs) in MM is clearly established, the function of the noncoding RNAome, which might allow the design of novel therapeutics, is largely unknown. We performed an unbiased CRISPR-Cas9 loss-of-function screen of 671 lncRNAs in MM cells and their bortezomib (BZB)-resistant derivative.

Chemometrics-based analysis of the phytochemical profile and antioxidant activity of Salvia species from Iran.

In recent years, the exploration of the therapeutic potential of Salvia has gained considerable attention, leading to a growing number of scientific studies emphasizing its pharmacological properties. Despite this, therapeutic applications of Salvia remain underexploited, requiring further investigation. Iran is a major center for sage diversity in Asia, boasting 60 Salvia species, 17 of which are unique to the area.

Development of a multi-targeted chemotherapeutic approach based on G-quadruplex stabilisation and carbonic anhydrase inhibition.

A novel class of compounds designed to hit two anti-tumour targets, G-quadruplex structures and human carbonic anhydrases (hCAs) IX and XII is proposed. The induction/stabilisation of G-quadruplex structures by small molecules has emerged as an anticancer strategy, disrupting telomere maintenance and reducing oncogene expression. hCAs IX and XII are well-established anti-tumour targets, upregulated in many hypoxic tumours and contributing to metastasis.

Unlocking the potential of protein-derived peptides to target G-quadruplex DNA: from recognition to anticancer activity.

Noncanonical nucleic acid structures, particularly G-quadruplexes, have garnered significant attention as potential therapeutic targets in cancer treatment. Here, the recognition of G-quadruplex DNA by peptides derived from the Rap1 protein is explored, with the aim of developing novel peptide-based G-quadruplex ligands with enhanced selectivity and anticancer activity. Biophysical techniques were employed to assess the interaction of a peptide derived from the G-quadruplex-binding domain of the protein with various biologically relevant G-quadruplex structures.

Chemistry and Biology of Noncanonical Nucleic Acid Structures: From Physicochemical Properties to Therapeutic Applications.

The aim of this Special Issue is to highlight significant and new aspects concerning the chemistry and biology of noncanonical nucleic acid structures, with emphasis on their structure, stability, and conformational equilibria, as well as on the biological relevance of their interactions with proteins and ligands [...

Caries experience, obesity and demographic factors in school children: A cluster analysis.

Objective: To determine the association between caries experience, obesity, and socioeconomic and environmental factors in 2, 5 and 12 years-old schoolchildren. Secondarily, the influence of school infrastructure was assessed.

Methods: Primary data from 1762 schoolchildren from the municipality of Cajamar (SP, Brazil) and socioeconomic and environmental secondary data (Brazilian Census 2010, School Census, Prova Brasil/2017) were used.

Efficacy of Liposuction in the Treatment of Lipedema: A Meta-Analysis.

Lipedema, a chronic and painful disorder primarily affecting women without a definitive cure, has traditionally been managed with conservative therapy, notably complete decongestive therapy, across many countries. Recently, liposuction has been explored as a potential surgical treatment, prompting this study to evaluate its effectiveness as possibly the first-line therapy for lipedema. Through extensive literature searches in databases such as CrossRef, Web of Science, PubMed, and Google Scholar up to December 2023, and using the Newcastle-Ottawa Scale for quality assessment, the study selected seven studies for inclusion.

High infestation and phylogenetic position of Epistylis sp. (Ciliophora, Peritrichia) on Aegla serrana Buckup & Rossi (Crustacea, Anomura) from southern Brazil.

High infestations of epibiont ciliates on vertebrates or invertebrates are normally related to aquaculture tanks or similar environments, and the importance of this relationship in natural habitats is often disregarded. Here, we describe the first record of high infestation of ciliates on Aegla serrana in South America and conduct a brief morphological and phylogenetic characterization of these ciliates. Our findings confirm that cases of high infestation of ciliates on metazoans can indeed occur in natural environments.

Exploring the DNA-PNA heterotriplex formation in targeting the Bcl-2 gene promoter: A structural insight by physico-chemical and microsecond-scale MD investigation.

Peptide Nucleic Acids (PNAs) represent a promising tool for gene modulation in anticancer treatment. The uncharged peptidyl backbone and the resistance to chemical and enzymatic degradation make PNAs highly advantageous to form stable hybrid complexes with complementary DNA and RNA strands, providing higher stability than the corresponding natural analogues. Our and other groups' research has successfully shown that tailored PNA sequences can effectively downregulate the expression of human oncogenes using antigene, antisense, or anti-miRNA approaches.

Discovery of 2,3-Diaminoindole Derivatives as a Novel Class of NOD Antagonists.

NOD1 and NOD2 are members of the pattern recognition receptors involved in the innate immune response. Overactivation of NOD1 is implicated in inflammatory disorders, multiple sclerosis, and cancer cell metastases. NOD1 antagonists would represent valuable pharmacological tools to gain further insight into protein roles, potentially leading to new therapeutic strategies.

A combined approach of structure-based virtual screening and NMR to interrupt the PD-1/PD-L1 axis: Biphenyl-benzimidazole containing compounds as novel PD-L1 inhibitors.

Immunotherapy has emerged as a game-changing approach for cancer treatment. Although monoclonal antibodies (mAbs) targeting the programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1) axis have entered the market revolutionizing the treatment landscape of many cancer types, small molecules, although presenting several advantages including the possibility of oral administration and/or reduced costs, struggled to enter in clinical trials, suffering of water insolubility and/or inadequate potency compared with mAbs. Thus, the search for novel scaffolds for both the design of effective small molecules and possible synergistic strategies is an ongoing field of interest.

Biosymbiotic platform for chronic long-range monitoring of biosignals in limited resource settings.

Remote patient monitoring is a critical component of digital medicine, and the COVID-19 pandemic has further highlighted its importance. Wearable sensors aimed at noninvasive extraction and transmission of high-fidelity physiological data provide an avenue toward at-home diagnostics and therapeutics; however, the infrastructure requirements for such devices limit their use to areas with well-established connectivity. This accentuates the socioeconomic and geopolitical gap in digital health technology and points toward a need to provide access in areas that have limited resources.

Effectiveness of a manual test at the beginning of dental school.

Introduction: This study analysed whether the SAZAMED (Self-assessment for dentistry studies) manual test conducted as an exercise or examination in the first year of dental studies, and the official aptitude test for medical studies (EMS), can predict future performance of dental students.

Materials And Methods: Students enrolled in the dental curriculum at the University of Basel between 2009/10 and 2019/20 were categorized: Group A conducted the SAZAMED in the third bachelor year (BA) and second master year (MA), group B practiced in the first and third BA and second MA and group C had to pass the test in the first BA with repetition in the third BA and second MA. SAZAMED comprised (i) wire bending, (ii) modelling sphere and cube, (iii) drawing mirror-inverted and (iv) indirect drawing over a mirror.