Cell Signaling

Two distinct, but intertwining, threads of inquiry have demonstrated that the PDE4, or cAMP-selective, phosphodiesterases, have an essential role in human cognition, learning and memory. Study of genetically-modified preclinical models, and of humans with mutations in the PDE4D gene, has provided some of the most rigorous proof of the importance of PDE4 signaling in the CNS. More recently, clinical trials of PDE4-selective inhibitors have shown promising clinical activity in disorders of cognition and memory.

Cancer is a leading cause of childhood mortality, with rhabdomyosarcoma (RMS) being the most prevalent type diagnosed in approximately two-thirds of pediatric cancer cases, particularly the embryonal subtype. RMS represents the most common soft tissue sarcoma in children and adolescents, accounting for around 2-3.5% of all pediatric malignancies [1].

Hemodialysis is the most common form of kidney replacement worldwide. It is expected that the acceptance rate of hemodialysis will continue to increase in the coming decades [1]. About 89% of dialysis patients worldwide receive hemodialysis. The majority of these patients are living in high-income countries or middle to high-income countries such as Brazil and South Africa.

Interferons (IFNs) are a class of small immunological proteins that are secreted by infected cells during viral or bacterial infections to combat and prevent infection propagation [1]. They play important roles in triggering signal cascade processes inside the cell that activate other immune cells and limit viral multiplication.

Acne vulgaris, the most common skin condition worldwide, affects over 85% of adolescents, with nearly half continuing to experience it into adulthood. The Scarring and post-inflammatory hyperpigmentation associated with acne can profoundly impact mental health and self-esteem, underscoring the importance of early and effective treatment [1].

Parkinson’s disease (PD), a progressive neurodegenerative disorder, characterized by clinical features such as bradykinesia and resting tremor. It is characterized by specific neuropathological changes. These changes include the degeneration of dopaminergic neurons in the substantia nigra (SN) pars compacta.

Stress granules (SGs) are dynamic, membraneless organelles that assemble in response to cellular stress, such as oxidative stress, hypoxia, or nutrient deprivation [1,2]. Protein translation typically is halted under stress conditions, leading to assembly of SGs containing mRNAs, RNA-binding proteins (RBPs), and other proteins.

Aging is an inevitable biological process that significantly affects various organs, including the heart. Cardiac aging, with its associated structural and functional changes, can lead to left ventricular (LV) hypertrophy, diastolic dysfunction, increased arterial stiffness, and reduced overall cardiac functional reserve [1,2].

MPNSTs are aggressive Schwann cell-derived sarcomas, frequently associated with NF1 mutations. Traditional treatments, including surgery and chemotherapy, are largely ineffective, highlighting the urgent need for novel therapeutic strategies. NF1 loss leads to RAS pathway activation, which in turn activates multiple signaling cascades, including RAF-MEK-ERK1/2, PI3K-AKT, and RalGDS pathways. Inhibition of these pathways has been explored, with MEK inhibitors, such as selumetinib, showing some promise in clinical trials (NCT03433183).

Apart from alcohol and other definitive factors, metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a clinicalpathological syndrome characterized by hepatic steatosis and lipid accumulation.

Periodontitis is a chronic inflammatory disease that affects more than 40% of the adult population aged over 30 years in the United States, indicating a high prevalence [1]. It impairs the integrity of the tooth-supporting tissue with clinical manifestations featured of gingiva bleeding, periodontal ligament degradation, and alveolar bone resorption. Periodontitis is a multifactorial disease, involving interactions of bacterial pathogens, host immune responses and environmental factors such as smoking [2].