Effects of chemical activation versus fragmentation on human ovarian tissue and follicle growth in culture.

Study Question: What is the effect of the chemical activation (cIVA) protocol compared with fragmentation only (Frag, also known as mechanical IVA) on gene expression, follicle activation and growth in human ovarian tissue ?

Summary Answer: Although histological assessment shows that cIVA significantly increases follicle survival and growth compared to Frag, both protocols stimulate extensive and nearly identical transcriptomic changes in cultured tissue compared to freshly collected ovarian tissue, including marked changes in energy metabolism and inflammatory responses.

What Is Known Already: Treatments based on cIVA of the phosphatase and tensin homolog (PTEN)-phosphatidylinositol 3-kinase (PI3K) pathway in ovarian tissue followed by auto-transplantation have been administered to patients with refractory premature ovarian insufficiency (POI) and resulted in live births. However, comparable effects with mere tissue fragmentation have been shown, questioning the added value of chemical stimulation that could potentially activate oncogenic responses.

Exposure to the phthalate metabolite MEHP impacts survival and growth of human ovarian follicles in vitro.

Phthalates are found in everyday items like plastics and personal care products. There is an increasing concern that continuous exposure can adversely affect female fertility. However, experimental data are lacking to establish causal links between exposure and disease in humans.

Exploring the immunomodulatory properties of glucan particles in human primary cells.

The immunomodulatory properties of β-glucans have sparked interest among various medical fields. As vaccine adjuvants, glucan particles offer additional advantages as antigen delivery systems. This study reported the immunomodulatory properties of glucan particles with different size and chemical composition.

Microfluidic-based skin-on-chip systems for safety assessment of nanomaterials.

The skin is the body's largest organ, continuously exposed to and affected by natural and anthropogenic nanomaterials (materials with external and internal dimensions in the nanoscale range). This broad spectrum of insults gives rise to irreversible health effects (from skin corrosion to cancer). Organ-on-chip systems can recapitulate skin physiology with high fidelity and potentially revolutionize the safety assessment of nanomaterials.

Macrophage innate training induced by IL-4 and IL-13 activation enhances OXPHOS driven anti-mycobacterial responses.

Macrophages are a highly adaptive population of innate immune cells. Polarization with IFNγ and LPS into the 'classically activated' M1 macrophage enhances pro-inflammatory and microbicidal responses, important for eradicating bacteria such as . By contrast, 'alternatively activated' M2 macrophages, polarized with IL-4, oppose bactericidal mechanisms and allow mycobacterial growth.

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment.

The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drugs, food, water treatment, and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity, and (epi)genotoxicity.

Mycobacterial -Hydroxybenzoic Acid-Derivatives (HBADs) and Related Structures Induce Macrophage Innate Memory.

Macrophages are key immune cells for combatting . However, possesses means to evade macrophage bactericidal responses by, for instance, secretion of the immunomodulatory -hydroxybenzoic acid derivatives (HBADs). While these molecules have been implicated in inhibiting macrophage responses in an acute context, little is known about their ability to reprogram macrophages via induction of long-term innate memory.

Pristine graphene induces innate immune training.

Graphene-based materials are of increasing interest for their potential use in biomedical applications. However, there is a need to gain a deeper understanding of how graphene modulates biological responses before moving towards clinical application. Innate immune training is a recently described phenomenon whereby cells of the innate immune system are capable of being programmed to generate an increased non-specific response upon subsequent challenge.

Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease.

Background: The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs).

Objectives: We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease.

Easy and effective method to generate endotoxin-free chitosan particles for immunotoxicology and immunopharmacology studies.

Objectives: The cationic biopolymer chitosan (CH) has emerged as a promising candidate adjuvant due to its safety profile and immunostimulatory properties. The presence of endotoxin contamination in biomaterials is generally underappreciated and can generate misleading results. It is important to establish a convenient methodology to obtain large amounts of high quality chitosan nanoparticles for biomedical applications.

Chitosan Plus Compound 48/80: Formulation and Preliminary Evaluation as a Hepatitis B Vaccine Adjuvant.

Current vaccine research is mostly based on subunit antigens. Despite the better toxicity profile of these antigens they are often poorly immunogenic, so adjuvant association has been explored as a strategy to obtain a potent vaccine formulation. Recently, mast cell activators were recognized as a new class of vaccine adjuvants capable of potentiating mucosal and systemic immune responses.

Mechanistic study of the adjuvant effect of chitosan-aluminum nanoparticles.

The use of tailored particle-based adjuvants constitutes a promising way to enhance antigen-specific humoral and cellular immune responses. However, a thorough understanding of the mechanisms underlying their adjuvanticity is crucial to generate more effective vaccines. We studied the ability of chitosan-aluminum nanoparticles (CH-Al NPs), which combine the immunostimulatory effects of chitosan and aluminum salts, to promote dendritic cell activation, assess their impact on innate and adaptive immune responses, and compare the results to those reported for conventional chitosan particles (CH-Na NPs).

The Na -coupled glucose transporter SGLT2 interacts with its accessory unit MAP17 in vitro and their expressions overlap in the renal proximal tubule.

Na -glucose cotransporter 2 is the renal Na -coupled glucose transporter responsible for the tubular glucose reabsorption, while MAP17 was recently identified as its accessory unit. Mutations in either of the proteins' coding genes, SLC5A2 and PDZK1IP1, lead to urinary glucose excretion. To investigate whether MAP17 interacts with SGLT2 in vitro, we engineered a V5-tagged SGLT2 construct and evaluated HEK293T cells coexpressing it together with a HA tagged MAP17 construct.

The shape and size of hydroxyapatite particles dictate inflammatory responses following implantation.

The extent of regeneration following biomaterial implantation is dependent on the microenvironment surrounding the implant. Since implant composition can have a profound effect on inflammation, it is essential to understand this process as a non-resolving inflammatory response can lead to fibrous encapsulation and insufficient integration. Incorporation of particulates into implants confers structural and functional benefits, thus optimizing particulate characteristics to enhance immune mediated efficacy is important.

Association of chitosan and aluminium as a new adjuvant strategy for improved vaccination.

The use of particulate adjuvants offers an interesting possibility to enhance and modulate the immune responses elicited by vaccines. Aluminium salts have been extensively used as vaccine adjuvants, but they lack the capacity to induce a strong cellular and mucosal immune response. Taking this into consideration, in this study we designed a new antigen delivery system combining aluminium salts with chitosan.

Modulation of Immune Responses by Particulate Materials.

Many biomaterials that are in both preclinical and clinical use are particulate in nature and there is a growing appreciation that the physicochemical properties of materials have a significant impact on their efficacy. The ability of particulates to modulate adaptive immune responses has been recognized for the past century but it is only in recent decades that a mechanistic understanding of how particulates can regulate these responses has emerged. It is now clear that particulate characteristics including size, charge, shape and porosity can influence the scale and nature of both the innate and adaptive immune responses.

Intranasal Administration of Novel Chitosan Nanoparticle/DNA Complexes Induces Antibody Response to Hepatitis B Surface Antigen in Mice.

The generation of strong pathogen-specific immune responses at mucosal surfaces where hepatitis B virus (HBV) transmission can occur is still a major challenge. Therefore, new vaccines are urgently needed in order to overcome the limitations of existing parenteral ones. Recent studies show that this may be achieved by intranasal immunization.

Chitosan-based nanoparticles as a hepatitis B antigen delivery system.

The design of antigen delivery systems, particularly for mucosal surfaces, has been a focus of interest in recent years. In this chapter, we describe the preparation of chitosan-based particles as promising antigen delivery systems for mucosal surfaces already tested by our group with hepatitis B surface antigen. The final proof of the concept is always carried out with immunization studies performed in an appropriate animal model.

Progress towards a needle-free hepatitis B vaccine.

Hepatitis B virus (HBV) infection is a worldwide public health problem. Vaccination is the most efficient way to prevent hepatitis B. Despite the success of the currently available vaccine, there is a clear need for the development of new generation of HBV vaccines.

Mucosal vaccines: recent progress in understanding the natural barriers.

It has long been known that protection against pathogens invading the organism via mucosal surfaces correlates better with the presence of specific antibodies in local secretions than with serum antibodies. The most effective way to induce mucosal immunity is to administer antigens directly to the mucosal surface. The development of vaccines for mucosal application requires antigen delivery systems and immunopotentiators that efficiently facilitate the presentation of the antigen to the mucosal immune system.