Non-Alcoholic Steatohepatitis Patient Characterization and Real-World Management Approaches in Italy.

Background: Although the estimated prevalence of non-alcoholic steatohepatitis (NASH) in Italy is 4-6%, little is known about patient characteristics and care pathways.

Aim: To describe patient characteristics and management approaches for patients with NASH or suspected NASH in Italy.

Methods: Data were drawn from the Adelphi Real World NASH Disease Specific Programme™, a cross-sectional survey of endocrinologists and gastroenterologists in Italy from January to March 2018.

SPIRIT: Assessing Clinical Parameters Associated with Using IDegLira in Patients with Type 2 Diabetes in a Real-World Setting in Colombia.

Introduction: Insulin degludec/liraglutide (IDegLira) is a fixed-ratio combination of insulin degludec (a basal insulin) and liraglutide (a glucagon-like peptide-1 receptor agonist [GLP-1RA]). This study aimed to investigate clinical outcomes in people with type 2 diabetes mellitus (T2DM) after initiating IDegLira treatment in a real-world setting in Colombia.

Methods: SPIRIT is a non-interventional, single-arm, retrospective chart review study to assess clinical outcomes in people with T2DM.

A cross-sectional study of the prevalence and clinical management of atherosclerotic cardiovascular diseases in patients with type 2 diabetes across the Middle East and Africa (PACT-MEA): Study design and rationale.

Aim: To investigate the epidemiology and clinical management of patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (eASCVD) or high/very high ASCVD risk, defined by the 2021 European Society of Cardiology Guidelines, in seven countries in the Middle East and Africa (PACT-MEA; NCT05317845), and to assess physicians' attitudes and the basis for their decision-making in the management of these patients.

Materials And Methods: PACT-MEA is a cross-sectional, observational study undertaken in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa and the United Arab Emirates based on a medical chart review of approximately 3700 patients with T2D in primary and secondary care settings, and a survey of approximately 400 physicians treating patients with T2D.

Results: The primary and secondary objectives are to determine the prevalence of eASCVD and high/very high ASCVD risk in patients with T2D.

Dual-targeted hybrid nanoparticles of synergistic drugs for treating lung metastases of triple negative breast cancer in mice.

Lung metastasis is the major cause of death in patients with triple negative breast cancer (TNBC), an aggressive subtype of breast cancer with no effective therapy at present. It has been proposed that dual-targeted therapy, ie, targeting chemotherapeutic agents to both tumor vasculature and cancer cells, may offer some advantages. The present work was aimed to develop a dual-targeted synergistic drug combination nanomedicine for the treatment of lung metastases of TNBC.

Manganese oxide and docetaxel co-loaded fluorescent polymer nanoparticles for dual modal imaging and chemotherapy of breast cancer.

Multifunctional nanoparticles (NPs) have found important applications in diagnosis, chemotherapy, and image-guided surgery of tumors. In this work, we have developed polymeric theranostic NPs (PTNPs) containing the anticancer drug docetaxel (DTX), a fluorescent dye, and magnetic manganese oxide (MnO) NPs for dual modal imaging and chemotherapy. PTNPs ~150 nm in diameter were synthesized by co-loading hydrophobic DTX and MnO NPs ~5 nm in diameter, into the matrix of a fluorescent dye-labeled amphiphilic polymer.

RGD-conjugated solid lipid nanoparticles inhibit adhesion and invasion of αvβ3 integrin-overexpressing breast cancer cells.

αvβ3 integrin receptors expressed on cancer cell surfaces play a crucial role in promoting tumor angiogenesis and cancer cell metastasis. Thus, cyclic arginyl-glycyl-aspartic acid (cRGD) peptides have been explored as a αvβ3 integrin receptor-specific targeting moiety for the targeted delivery of nanoparticle-loaded therapeutics. However, our previous study showed that cyclic RGD could act as a double-edged sword that, on one hand, extended the retention of cRGD-modified solid lipid nanoparticles (RGD-SLNs) at αvβ3 integrin receptor overexpressing breast carcinoma, and yet on the other hand, decreased the amount of tumor accumulation of RGD-SLNs attributable to the greater uptake by the mononuclear phagocyte system (MPS).

A multifunctional polymeric nanotheranostic system delivers doxorubicin and imaging agents across the blood-brain barrier targeting brain metastases of breast cancer.

Metastatic brain cancers, in particular cancers with multiple lesions, are one of the most difficult malignancies to treat owing to their location and aggressiveness. Chemotherapy for brain metastases offers some hope. However, its efficacy is severely limited as most chemotherapeutic agents are incapable of crossing the blood-brain barrier (BBB) efficiently.

Synergistic nanoparticulate drug combination overcomes multidrug resistance, increases efficacy, and reduces cardiotoxicity in a nonimmunocompromised breast tumor model.

Anthracyclines, commonly employed for cancer chemotherapy, suffer from dose-limiting cardiotoxicity and poor efficacy due to multidrug resistance (MDR). We previously demonstrated that simultaneous delivery of the synergistic drugs doxorubicin (DOX) and mitomycin C (MMC) by polymer-lipid hybrid nanoparticles (PLN) circumvented MDR, increased efficacy, and reduced cardiotoxicity in immuncompromised mice superior to poly(ethylene glycol)-coated (PEGylated) lipososmal DOX (PLD). Herein it is shown that the DOX-MMC combination was also synergistic in MDR EMT6/AR1 murine breast cancer cells and that their nanoparticle formulations were able to overcome the MDR phenotype.

Multifunctional albumin-MnO₂ nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response.

Insufficient oxygenation (hypoxia), acidic pH (acidosis), and elevated levels of reactive oxygen species (ROS), such as H2O2, are characteristic abnormalities of the tumor microenvironment (TME). These abnormalities promote tumor aggressiveness, metastasis, and resistance to therapies. To date, there is no treatment available for comprehensive modulation of the TME.

Matrigel alters the pathophysiology of orthotopic human breast adenocarcinoma xenografts with implications for nanomedicine evaluation.

Unlabelled: Matrigel, a mouse sarcoma-derived basement membrane protein mixture, is frequently used to facilitate human tumor xenograft growth in rodents. Despite its known effects on tumor growth and metastasis, its impact on tumor pathophysiology and preclinical evaluation of nanomedicines in tumor xenografts has not been reported previously. Herein bilateral MDA435 tumors were established orthotopically with (Mat+) or without (Mat-) co-injection of Matrigel.

A novel solid lipid nanoparticle formulation for active targeting to tumor α(v) β(3) integrin receptors reveals cyclic RGD as a double-edged sword.

The overexpression of α(v) β(3) integrin receptors on tumor cells and tumor vascular endothelium makes it a useful target for imaging, chemotherapy and anti-angiogenic therapy. However integrin-targeted delivery of therapeutics by nanoparticles have provided only marginal, if any, enhancement of therapeutic effect. This work was thus focused on the development of novel α(v) β(3) -targeted near infrared light-emitting solid lipid nanoparticles (SLN) through conjugation to the α(v) β(3) integrin-specific ligand cyclic Arg-Gly-Asp (cRGD), and the assessment of the effects of α(v) β(3) targeting on nanoparticle biodistribution.

Doxorubicin and mitomycin C co-loaded polymer-lipid hybrid nanoparticles inhibit growth of sensitive and multidrug resistant human mammary tumor xenografts.

Multidrug resistance (MDR) and drug toxicity are two major factors responsible for the failure of cancer chemotherapy. Herein the efficacy and safety of combination therapy using doxorubicin (Dox, D)-mitomycin C (MMC, M) co-loaded stealth polymer-lipid hybrid nanoparticles (DMsPLNs) were evaluated in sensitive and MDR human mammary tumor xenografts. DMsPLN demonstrated enhanced efficacy compared to liposomal Dox (PLD) with up to a 3-fold increase in animal life span, a 10-20% tumor cure rate, undetectable normal tissue toxicity and decreased tumor angiogenesis.

A novel nanoparticle formulation overcomes multiple types of membrane efflux pumps in human breast cancer cells.

Multidrug resistance (MDR) in cancer cells can involve overexpression of different types of membrane drug efflux pumps and other drug resistance mechanisms. Hence, inhibition of one resistance mechanism may not be therapeutically effective. Previously we demonstrated a new polymer lipid hybrid nanoparticle (PLN) system was able to circumvent drug resistance of P-glycoprotein (P-gp) overexpressing breast cancer cells.

Classification of cell types using a microfluidic device for mechanical and electrical measurement on single cells.

This paper presents a microfluidic system for cell type classification using mechanical and electrical measurements on single cells. Cells are aspirated continuously through a constriction channel with cell elongations and impedance profiles measured simultaneously. The cell transit time through the constriction channel and the impedance amplitude ratio are quantified as cell's mechanical and electrical property indicators.

Colloidally stable silicon nanocrystals with near-infrared photoluminescence for biological fluorescence imaging.

Luminescent silicon nanocrystals (ncSi) are showing great promise as photoluminescent tags for biological fluorescence imaging, with size-dependent emission that can be tuned into the near-infrared biological window and reported lack of toxicity. Here, colloidally stable ncSi with NIR photoluminescence are synthesized from (HSiO1.5)n sol-gel glasses and are used in biological fluorescence imaging.

Hybrid quantum dot-fatty ester stealth nanoparticles: toward clinically relevant in vivo optical imaging of deep tissue.

Despite broad applications of quantum dots (QDs) in vitro, severe toxicity and dominant liver uptake have limited their clinical application. QDs that excite and emit in the ultraviolet and visible regions have limited in vivo applicability due to significant optical interference exerted by biological fluids and tissues. Hence we devised a new biocompatible hybrid fluorophore composed of near-infrared-emitting PbSe quantum dots encapsulated in solid fatty ester nanoparticles (QD-FEN) for in vivo imaging.