Plant Resin Delivery by Nanovectors as an Emerging Approach to Boost Solubility, Permeability and Bioavailability.

Resins are complex mixtures of natural constituents containing non-volatile and volatile terpenes, in combination with gums and polyphenols, used since ancient times for their medicinal properties. Current research has evidenced their therapeutic value with a plethora of activities. The main limits of resins and their constituents for their clinical use are low water solubility, poor stability and bioavailability.

Formulation, Characterization, and Antioxidant Properties of Chitosan Nanoparticles Containing Phenolic Compounds from Olive Pomace.

Olive phenolic compounds like hydroxytyrosol (OH-Tyr), tyrosol (Tyr), and their precursors have different health-promoting properties, mainly based on their strong antioxidant capacity. However, their presence in extra-virgin olive oil (EVOO) is scarce since they are primarily contained in the by-products of oil production, such as olive pomace (OP). The aim of this work was to extract and encapsulate OP phenolic compounds into chitosan-tripolyphosphate nanoparticles (NPs) using an ionotropic gelation lyophilization approach to increase their resistance to environmental and chemical stress.

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Discovery of 6-Fluoro-5-{4-[(5-fluoro-2-methyl-3-oxo-3,4-dihydroquinoxalin-6-yl)methyl]piperazin-1-yl}--methylpyridine-2-carboxamide (AZD9574): A CNS-Penetrant, PARP1-Selective Inhibitor.

PARP inhibitors have attracted considerable interest in drug discovery due to the clinical success of first-generation agents such as olaparib, niraparib, rucaparib, and talazoparib. Their success lies in their ability to trap PARP to DNA; however, first-generation PARP inhibitors were not strictly optimized for trapping nor for selectivity among the PARP enzyme family. Previously we described the discovery of the second-generation PARP inhibitor AZD5305, a selective PARP1-DNA trapper.

Personalized Sound Therapy Combined with Low and High-Frequency Electromagnetic Stimulation for Chronic Tinnitus.

This study investigates a novel multimodal treatment for chronic tinnitus, a condition that significantly affects quality of life, by combining personalized sound therapy with both low- and high-frequency electromagnetic wave stimulation. Conducted at Tor Vergata University Hospital in Rome, the research involved 55 patients and employed a portable medical device for therapy delivery. Treatment effectiveness was measured through the Tinnitus Functional Index (TFI), Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), Hyperacusis Questionnaire (HQ), and Short Form-36 Health Survey (SF-36), encompassing initial sound therapy and subsequent multimodal treatment phases.

The PARP1 selective inhibitor saruparib (AZD5305) elicits potent and durable antitumor activity in patient-derived BRCA1/2-associated cancer models.

Background: Poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors (PARPi) are targeted therapies approved for homologous recombination repair (HRR)-deficient breast, ovarian, pancreatic, and prostate cancers. Since inhibition of PARP1 is sufficient to cause synthetic lethality in tumors with homologous recombination deficiency (HRD), PARP1 selective inhibitors such as saruparib (AZD5305) are being developed. It is expected that selective PARP1 inhibition leads to a safer profile that facilitates its combination with other DNA damage repair inhibitors.

Long-term effects of luteolin in a mouse model of nephropathic cystinosis.

In infantile nephropathic cystinosis, variants of the CTNS gene cause accumulation of cystine in lysosomes, causing progressive damage to most organs. Patients usually present before 1 year of age with signs of renal Fanconi syndrome. Cysteamine therapy allows cystine clearance from lysosomes and delays kidney damage but does not prevent progression to end-stage kidney disease, suggesting that pathways unrelated to cystine accumulation are also involved.

Plasmonic Modulators in Cryogenic Environment Featuring Bandwidths in Excess of 100 GHz and Reduced Plasmonic Losses.

Cryogenic quantum applications have a demand for an ever-higher number of interconnects and bandwidth. Photonic links are foreseen to offer data transfer with high bandwidth, low heat load, and low noise to enable the next-generation scalable quantum computing systems. However, they require high-speed and energy-efficient modulators operating at cryogenic temperatures for electro-optic signal conversion.

Ketogenic Diet and Progression of Kidney Disease in Animal Models of Nephropathic Cystinosis.

Key Points: Ketogenic diet can change the metabolism in the body and helped restore the function of altered pathways in nephropathic cystinosis. Ketogenic diet had significant benefits for preventing kidney damage, even when initiated after the onset of kidney impairment. Ketogenic diet may provide a partial therapeutic alternative in countries where cysteamine therapy is too expensive.

deletion ameliorates kidney damage in a mouse model of cystinosis.

Cystinosis is a rare autosomal recessive disorder caused by mutations in the gene that encodes cystinosin, a ubiquitous lysosomal cystine/H antiporter. The hallmark of the disease is progressive accumulation of cystine and cystine crystals in virtually all tissues. At the kidney level, human cystinosis is characterized by the development of renal Fanconi syndrome and progressive glomerular and interstitial damage leading to end-stage kidney disease in the second or third decade of life.

A phase Ib/II trial of capmatinib plus spartalizumab spartalizumab alone in patients with pretreated hepatocellular carcinoma.

Background & Aims: This phase Ib/II trial evaluated the safety and efficacy of capmatinib in combination with spartalizumab or spartalizumab alone in patients with advanced hepatocellular carcinoma (HCC).

Methods: Eligible patients who had progressed or were intolerant to sorafenib received escalating doses of capmatinib 200 mg, 300 mg, and 400 mg twice a day (bid) plus spartalizumab 300 mg every 3 weeks (q3w) in the phase Ib study. Once the recommended phase II dose (RP2D) was determined, the phase II study commenced with randomised 1:1 treatment with either capmatinib + spartalizumab (n = 32) or spartalizumab alone (n = 30).

Inflammatory-Targeted Lipid Carrier as a New Nanomaterial to Formulate an Inhaled Drug Delivery System.

There is a pressing need for efficacious therapies in the field of respiratory diseases and infections. Lipid nanocarriers, administered through aerosols, represent a promising tool for maximizing therapeutic concentration in targeted cells and minimizing systemic exposure. However, this approach requires the application of efficient and safe nanomaterials.

The use of andexanet alfa vs. 4-factor prothrombin complex concentrates in the setting of life-threatening intracranial hemorrhage.

Objective: Andexanet alfa is a targeted reversal agent for life threatening hemorrhage associated with direct acting oral anticoagulants (DOACs), but there is uncertainty regarding the benefit when compared to 4-factor prothrombin complex concentrate (4F-PCC) for this indication. We investigated the clinical outcomes and cost associated with reversal of DOACs in the setting of life-threatening intracranial hemorrhage (ICH).

Methods: A retrospective evaluation was conducted to evaluate patients with ICH in the setting of anticoagulation with DOAC from 9/1/2013 to 4/30/2020.

Combination of granulocyte-monocyte apheresis and tofacitinib: Multicentre and retrospective study.

Objective: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC.

Patients And Methods: Retrospective study including all patients with refractory UC who received GMA plus TOFA.

Artificial Intelligence and Radiomics for Endometrial Cancer MRI: Exploring the Whats, Whys and Hows.

Endometrial cancer (EC) is intricately linked to obesity and diabetes, which are widespread risk factors. Medical imaging, especially magnetic resonance imaging (MRI), plays a major role in EC assessment, particularly for disease staging. However, the diagnostic performance of MRI exhibits variability in the detection of clinically relevant prognostic factors (e.

Combination of Nanodelivery Systems and Constituents Derived from Novel Foods: A Comprehensive Review.

Novel Food is a new category of food, regulated by the European Union Directive No. 2015/2283. This latter norm defines a food as "Novel" if it was not used "for human consumption to a significant degree within the Union before the date of entry into force of that regulation, namely 15 May 1997".

Preclinical Characterization of AZD9574, a Blood-Brain Barrier Penetrant Inhibitor of PARP1.

Purpose: We evaluated the properties and activity of AZD9574, a blood-brain barrier (BBB) penetrant selective inhibitor of PARP1, and assessed its efficacy and safety alone and in combination with temozolomide (TMZ) in preclinical models.

Experimental Design: AZD9574 was interrogated in vitro for selectivity, PARylation inhibition, PARP-DNA trapping, the ability to cross the BBB, and the potential to inhibit cancer cell proliferation. In vivo efficacy was determined using subcutaneous as well as intracranial mouse xenograft models.

Relevance of ATM Status in Driving Sensitivity to DNA Damage Response Inhibitors in Patient-Derived Xenograft Models.

Ataxia-telangiectasia mutated gene (ATM) is a key component of the DNA damage response (DDR) and double-strand break repair pathway. The functional loss of ATM (ATM deficiency) is hypothesised to enhance sensitivity to DDR inhibitors (DDRi). Whole-exome sequencing (WES), immunohistochemistry (IHC), and Western blotting (WB) were used to characterise the baseline ATM status across a panel of ATM mutated patient-derived xenograft (PDX) models from a range of tumour types.

Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment.

Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy.

The PARP1 Inhibitor AZD5305 Impairs Ovarian Adenocarcinoma Progression and Visceral Metastases in Patient-derived Xenografts Alone and in Combination with Carboplatin.

Unlabelled: PARP inhibitors (PARPi) have changed the management of patients with ovarian cancer and their effectiveness has been demonstrated especially in homologous recombination repair-deficient tumors. These first-generation drugs target PARP1, but also PARP2 and other family members potentially responsible for adverse effects that limit their therapeutic potential and restrict their use in combination with chemotherapeutic agents. We investigated ovarian cancer patient-derived xenografts (OC-PDXs) to assess whether malignant progression could be impaired by a novel inhibitor selective for PARP1 (AZD5305) and to assess the potential of its combination with carboplatin (CPT), the standard-of-care for patients with ovarian cancer.

New Insights into the Role of Ferroptosis in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the principal cause of disease burden and death worldwide. Ferroptosis is a new form of regulated cell death mainly characterized by altered iron metabolism, increased polyunsaturated fatty acid peroxidation by reactive oxygen species, depletion of glutathione and inactivation of glutathione peroxidase 4. Recently, a series of studies have indicated that ferroptosis is involved in the death of cardiac and vascular cells and has a key impact on the mechanisms leading to CVDs such as ischemic heart disease, ischemia/reperfusion injury, cardiomyopathies, and heart failure.

Drug-gene Interaction Screens Coupled to Tumor Data Analyses Identify the Most Clinically Relevant Cancer Vulnerabilities Driving Sensitivity to PARP Inhibition.

Unlabelled: PARP inhibitors (PARPi) are currently indicated for the treatment of ovarian, breast, pancreatic, and prostate cancers harboring mutations in the tumor suppressor genes or . In the case of ovarian and prostate cancers, their classification as homologous recombination repair (HRR) deficient (HRD) or mutated also makes PARPi an available treatment option beyond or mutational status. However, identification of the most relevant genetic alterations driving the HRD phenotype has proven difficult and recent data have shown that other genetic alterations not affecting HRR are also capable of driving PARPi responses.