Anticancer potential of Bellardia trixago quantum dots: Cytotoxic effects on various cancer cell lines

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108340 - 108340

Published: March 1, 2025

Language: Английский

---

Validation of microphysiological systems for interpreting patient heterogeneity requires robust reproducibility analytics and experimental metadata

Cell Reports Methods, Journal Year: 2025, Volume and Issue: unknown, P. 101028 - 101028

Published: April 1, 2025

Multi-cell-type, 3D microphysiological systems (MPS) that recapitulate normal organ/organ system functions and the progression of diseases are being applied in drug discovery development programs to enable precision medicine. A critical step for this application is demonstrate reproducibility MPS its ability identify biologic/clinical heterogeneity from experimental variability, which requires capturing detailed metadata associated with studies as well a strong analytical approach assessing reproducibility. Detailed ensure identical study parameters compared when evaluating We have developed Pittsburgh protocol (PReP), uses set common statistical metrics, coefficient variation (CV), ANOVA, intraclass correlation (ICC), pipeline standard evaluate intra- interstudy performance. The PReP can be employed biological/clinical relevant

Language: Английский

---

Animal product-free formation and cultivation of 3D primary hepatocyte spheroids

Published: April 15, 2025

Abstract 3D cultures of primary human hepatocytes (3D PHH) are successfully used to reduce and replace the use animal experiments in biomedical research. Yet, initial formation PHH is highly dependent on supplementation with fetal bovine serum (FBS). However, molecular composition FBS its effects cultured cells poorly understood. Moreover, prone batch-to-batch variation, immunogenic risk lack adherence replacement, refinement, reduction (3Rs) experiments. Here, we demonstrate that can be fully replaced by animal-free substitutes, thus facilitating chemically defined serum-free cultures. Specifically, combined a previously developed substitute cocktail (Rafnsdóttir et al ., 2023) normoglycemic (5.5 mM glucose 0.58 ng/mL insulin) culture medium (Handin 2023). Morphological viability evaluations, along global proteomics data, demonstrated have equal or superior functional performance cytochrome P450s, rendering this useful for long-term studies vitro ADMET applications. This study marks significant advancement development conditions cell cultures, paving way more reliable ethical studies. Significance statement Most models rely leads inconsistent experimental results raises serious concerns. In our study, develop evaluate product-free physiologically relevant levels key hormones nutrients liver spheroid drug disposition

Language: Английский

---

Biosimilars Targeting Pathogens: A Comprehensive Review of Their Role in Bacterial, Fungal, Parasitic, and Viral Infections

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(5), P. 581 - 581

Published: April 28, 2025

Biosimilars represent medicinal products that exhibit a high degree of similarity to an already sanctioned reference biologic agent, with negligible clinically significant disparities concerning safety, purity, or potency. These therapeutic modalities are formulated as economically viable substitutes for established biologics, thereby facilitating increased accessibility sophisticated treatments range medical conditions, including infectious diseases caused by bacterial, fungal, and viral pathogens. The current landscape biosimilars includes proteins, such monoclonal antibodies, antimicrobial peptides, antiviral antifungal peptides. Here, we discuss the obstacles inherent in development biosimilars, rapid mutation rates Furthermore, innovative technologies within domain, antibody engineering, synthetic biology, cell-free protein synthesis, which potential improving potency production efficiency biosimilars. We end prospective outlook highlight importance capacity tackle emerging diseases, highlighting imperative need ongoing research financial commitment.

Language: Английский

---

Functional assessment of immortalized human brain microvascular endothelial cells with different passage numbers: A case study for a prospective proposal on variability management of in vitro blood-brain barrier models

Drug Metabolism and Pharmacokinetics, Journal Year: 2025, Volume and Issue: 62, P. 101058 - 101058

Published: Feb. 20, 2025

Language: Английский

---

Nano Plasma Membrane Vesicle‐Lipid Nanoparticle Hybrids for Enhanced Gene Delivery and Expression

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 10, 2024

Lipid nanoparticles (LNPs) have emerged as the leading nonviral nucleic acid (NA) delivery system, gaining widespread attention for their use in COVID-19 vaccines. They are recognized efficient NA encapsulation, modifiability, and scalable production. However, LNPs face efficacy potency limitations due to suboptimal intracellular processing, with endosomal escape efficiencies (ESE) below 2.5%. Additionally, up 70% of NPs undergo recycling exocytosis after cellular uptake. In contrast, cell-derived vesicles offer biocompatibility high-delivery but challenging load exogenous NAs manufacture at large-scale. To leverage strengths both systems, a hybrid system is designed by combining vesicles, such nano plasma membrane (nPMVs), through microfluidic mixing subsequent dialysis. These hybrids demonstrate tenfold increase ESE an 18-fold rise reporter gene expression vitro vivo zebrafish larvae (ZFL) mice, compared traditional LNPs. improvements linked unique physico-chemical properties, composition, morphology. By incorporating this strategy streamlines development process, significantly enhancing systems without need extensive screening.

Language: Английский

---

Advancements in Microphysiological Systems: Exploring Organoids and Organ-on-a-Chip Technologies in Drug Development -Focus on Pharmacokinetics Related Organs-

Drug Metabolism and Pharmacokinetics, Journal Year: 2024, Volume and Issue: 60, P. 101046 - 101046

Published: Dec. 17, 2024

This study explored the evolving landscape of Microphysiological Systems (MPS), with a focus on organoids and organ-on-a-chip (OoC) technologies, which are promising alternatives to animal testing in drug discovery. MPS technology offers vitro models high physiological relevance, simulating organ function for pharmacokinetic studies. Organoids composed 3D cell aggregates OoCs mimicking vivo environments based microfluidic platforms represent forefront MPS. paper provides comprehensive overview their application studying gut, liver, kidney challenges becoming reliable models. Although is not yet fully comparable systems, its continued development, aided by silico, automation, AI approaches, anticipated bring about further advancements. Collaboration across multiple disciplines ongoing regulatory discussions will be crucial driving toward practical ethical applications biomedical research development.

Language: Английский

---

Advanced In Vitro Models for Preclinical Drug Safety: Recent Progress and Prospects

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 47(1), P. 7 - 7

Published: Dec. 26, 2024

The majority of drugs are typically orally administered. journey from drug discovery to approval is often long and expensive, involving multiple stages. A major challenge in the development process drug-induced liver injury (DILI), a condition that affects liver, organ responsible for metabolizing most drugs. Traditionally, identifying DILI risk has been difficult due poor correlation between preclinical animal models vitro systems. Differences physiology humans animals or cell lines contribute failure many programs during clinical trials. use advanced systems closely mimic human physiology, such as organ-on-a-chip like gut-liver-on-a-chip, can be crucial improving efficacy while minimizing toxicity. Additionally, adaptation these technologies potential significantly reduce both time cost associated with obtaining safe approvals, all adhering 3Rs principle (replacement, reduction, refinement). In this review, we discuss significance, current status, future prospects platforms, specifically models, supporting discovery.

Language: Английский

---

Human Cardiac Development and Regeneration Modeling

Science Insights, Journal Year: 2024, Volume and Issue: 45(2), P. 1465 - 1474

Published: Aug. 29, 2024

Human cardiac development and regeneration modeling are crucial areas of research that hold immense promise for advancing regenerative medicine treating cardiovascular diseases. Understanding the intricate process development, from formation primitive heart tube to maturation fetal heart, provides insights into potential therapeutic strategies regeneration. This article explores key stages factors influencing regeneration, current models studying processes, challenges opportunities in medicine, future directions research, clinical applications modeling, implications healthcare. By delving these aspects, researchers healthcare professionals can gain a deeper understanding how harness human improved patient outcomes.

Language: Английский

---

A Zebrafish Embryo Model to Screen Potential Therapeutic Compounds in Sapindaceae Poisoning

Molecules, Journal Year: 2024, Volume and Issue: 29(20), P. 4954 - 4954

Published: Oct. 19, 2024

Hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG) are protoxins produced by

Language: Английский

---