In Silico Design of Dual Estrogen Receptor and Hsp90 Inhibitors for ER-Positive Breast Cancer Through a Mixed Ligand/Structure-Based Approach.

Breast cancer remains one of the most prevalent and lethal malignancies in women, particularly the estrogen receptor-positive (ER+) subtype, which accounts for approximately 70% of cases. Traditional endocrine therapies, including aromatase inhibitors, selective estrogen receptor degraders/antagonists (SERDs), and selective estrogen receptor modulators (SERMs), have improved outcomes for metastatic ER+ breast cancer. However, resistance to these agents presents a significant challenge.

Redox/NIR dual-responsive glutathione extended polyurethane urea electrospun membranes for synergistic chemo-photothermal therapy.

Despite advancements in cancer treatments, therapies frequently exhibit high cytotoxicity, and surgery remains the predominant method for treating most solid tumors, often with limited success in preventing post-surgical recurrence. Implantable biomaterials, designed to release drugs at a localised site in response to specific stimuli, represent a promising approach for enhancing tumour therapy. In this study, a redox-responsive glutathione extended polyurethane urea (PolyCEGS) was used to produce paclitaxel (PTX) and gold nanorods (AuNRs) loaded electrospun membranes for combined redox/near-infrared (NIR) light-responsive release chemotherapy and hyperthermic effect.

NOTCH3 variants of unknown significance underpin vascular dysfunction in neurodegenerative disease: a case series of three nfvPPA-FTD patients.

Introduction: The NOTCH3 gene encodes for an evolutionarily conserved protein, whose functions encompass both embryonic cell proliferation and adult tissue-specific differentiation. Among others, a pivotal role in maintaining functional integrity of neurovascular unit (NVU) is supported by the association of several NOTCH3 gene mutations with neuroimaging markers of cerebral small vessel disease (SVD). Indeed, a pathogenic role of NOTCH3 is recognised in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

A novel in silico approach for identifying multi-target JAK/STAT inhibitors as anticancer agents.

Apoptosis, or programmed cell death, plays a pivotal role in maintaining cellular homeostasis by eliminating damaged or surplus cells. Dysregulation of signaling pathways, such as JAK/STAT, is implicated in various diseases, rendering them attractive therapeutic targets for potential new anticancer drugs. Concurrently, it is imperative to preserve essential proteins like TNF-α and p53 to maintain normal cellular life/death balance.

Age of onset moderates the effects of Vascular Risk Factors on Neurodegeneration, Blood-Brain-Barrier permeability, and cognitive decline in Alzheimer's Disease.

Background: The role of Vascular risk factors (VRFs) in the progression of Alzheimer's Disease (AD) and cognitive decline remains to be elucidated, with previous studies resulting in conflicting findings. The possible impact of age-specific mechanisms of resilience/vulnerability is an under addressed issue. We evaluated the association of VRFs with markers of amyloid deposition, neurodegeneration, and blood-brain-barrier (BBB) permeability (Albumin quotient, Qalb), stratifying patients into early-onset (< 65, EOAD), classic late-onset (65-75, cLOAD) and very late-onset (> 75, vLOAD), to evaluate the moderating effect of age of onset.