The paradigm of pediatric drug development has been evolving in a “carrot-and-stick”-based tactic to address population-specific issues. However, the off-label prescription of adult medicines to pediatric patients remains a feature of clinical practice, which may compromise the age-appropriate evaluation of treatments. Therefore, the United States and the European Pediatric Formulation Initiative have recommended applying nanotechnology-based delivery systems to tackle some of these challenges, particularly applying inorganic, polymeric, and lipid-based nanoparticles. Connected with these, advanced therapy medicinal products (ATMPs) have also been highlighted, with optimistic perspectives for the pediatric population. Despite the results achieved using these innovative therapies, a workforce that congregates pediatric patients and/or caregivers, healthcare stakeholders, drug developers, and physicians continues to be of utmost relevance to promote standardized guidelines for pediatric drug development, enabling a fast lab-to-clinical translation. Therefore, taking into consideration the significance of this topic, this work aims to compile the current landscape of pediatric drug development by (1) outlining the historic regulatory panorama, (2) summarizing the challenges in the development of pediatric drug formulation, and (3) delineating the advantages/disadvantages of using innovative approaches, such as nanomedicines and ATMPs in pediatrics. Moreover, some attention will be given to the role of pharmaceutical technologists and developers in conceiving pediatric medicines.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the voltage-gated potassium channels or nucleotide-gated channels that participate in calcium and magnesium homeostasis. TRP channels allowing calcium to penetrate into nerve terminals can activate apoptosis, leading to nerve terminal destruction. Further, some TRPs are activated by acid and reactive oxygen species (ROS). ROS are mainly produced in the mitochondrial respiratory chain, and an increase in ROS production and/or a decrease in the antioxidant network may induce oxidative stress (OS). Depending on the OS levels, they can promote cellular proliferation and/or cell degeneration or death. Previous studies have indicated that proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play an important role in the peripheral mediation of neuropathic pain. This article aims to perform a review of the involvement of apoptosis in pain, particularly the role of OS and neuroinflammation, and the clinical relevance of this knowledge. The potential discovery of new biomarkers and therapeutic targets can result in the development of more effective and targeted drugs to treat chronic pain, namely neuropathic pain. Highlights: Oxidative stress and neuroinflammation can activate cell signaling pathways that can lead to nerve terminal destruction by apoptosis. These could constitute potential new pain biomarkers and targets for therapy in neuropathic pain.

The human microbiota comprises a group of microorganisms co-existing in the human body. Unbalanced microbiota homeostasis may impact metabolic and immune system regulation, shrinking the edge between health and disease. Recently, the microbiota has been considered a prominent extrinsic/intrinsic element of cancer development and a promising milestone in the modulation of conventional cancer treatments. Particularly, the oral cavity represents a yin-and-yang target site for microorganisms that can promote human health or contribute to oral cancer development, such as Fusobacterium nucleatum. Moreover, Helicobacter pylori has also been implicated in esophageal and stomach cancers, and decreased butyrate-producing bacteria, such as Lachnospiraceae spp. and Ruminococcaceae, have demonstrated a protective role in the development of colorectal cancer. Interestingly, prebiotics, e.g., polyphenols, probiotics (Faecalibacterium, Bifidobacterium, Lactobacillus, and Burkholderia), postbiotics (inosine, butyrate, and propionate), and innovative nanomedicines can modulate antitumor immunity, circumventing resistance to conventional treatments and could complement existing therapies. Therefore, this manuscript delivers a holistic perspective on the interaction between human microbiota and cancer development and treatment, particularly in aerodigestive and digestive cancers, focusing on applying prebiotics, probiotics, and nanomedicines to overcome some challenges in treating cancer.

Long-term illness, such as chronic obstructive pulmonary disease (COPD), can expose people to existential suffering that threatens their dignity. This qualitative study explored the lived experiences of patients with advanced COPD in relation to dignity. An interpretative phenomenological approach based on lifeworld existentials was conducted to explore and understand the world of the lived experience. Twenty individuals with advanced COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages III and IV) were selected using a purposive sampling strategy. In-depth interviews were used to collect data, which were then analysed using Van Manen’s phenomenology of practice. The existential experience of dignity was understood, in essence, as “a small candle flame that doesn’t go out!”. Four intertwined constituents illuminated the phenomenon: “Lived body–balancing between sick body and willingness to continue”; “Lived relations–balancing between self-control and belongingness”; “Lived Time–balancing between past, present and a limited future”; and “Lived space–balancing between safe places and non-compassionate places”. This study explains how existential life phenomena are experienced during the final phases of the COPD trajectory and provides ethical awareness of how dignity is lived. More research is needed to investigate innovative approaches to manage complex care in advanced COPD, in order to assist patients in discovering their inner resources to develop and promote dignity.