Current Molecular Pharmacology - Volume 16, Issue 4, 2023

Cancer is a leading cause of death and a severe threat to global public health. Organoid, as a novel 3D in vitro model, has been applied in various tumor related studies due to its apparent advantages. The organoid is mainly constructed by Matrigel-depended 3D culture system, Air-Liquid Interface (ALI) culture, and Microfluidic culture or Organ-on-chips platform. For the application in carcinogenesis studies, the organoid model may favor depicting initiative hallmarks and identifying potential intervening targets, investigating driver genes of carcinogenesis, and identifying known or unknown risk or protective factors. In this review, we discussed different organoid construction methods and their properties. We also noted that tumor organoids can portray initiative hallmarks and identify possible intervening targets, as well as explore carcinogenesis driver genes and uncover known or unknown risks or protective factors. Organoid systems have been used to identify tumor-preventive drugs such as oligomeric proanthocyanidins, Vitamin D, n-3 PUFAs, and pomegranate. The current evidence underscores the organoid model's potential importance in developing innovative tumorprevention techniques.

The increasing number of cases of diabetes mellitus (DM) and related diseases has become a global health concern. In this context, controlling blood glucose levels is critical to prevent and/or slow down the development of diabetes-related complications. Incretins, as gutderived hormones that trigger the post-meal secretion of insulin, are a well-known family of blood glucose modulators. Currently, incretin medications, including glucagon-like peptide-1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors, are extensively used to treat patients with type 2 diabetes mellitus (T2D). Several experimental and clinical studies illustrate that these metabolic hormones exert their antidiabetic effects through multiple molecular mechanisms. Accordingly, the current review aims to investigate key mechanisms and signaling pathways, such as the cAMP/PKA, Nrf2, PI3K/Akt, and AMPK pathways, associated with the antidiabetic effects of incretins. It also summarizes the outcomes of a group of clinical trials evaluating the incretins’ antidiabetic potential in diabetic patients.

Idiopathic Nephrotic Syndrome (INS) is the most frequent etiology of glomerulopathy in pediatric patients and one of the most common causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in this population. In this review, we aimed to summarize evidence on the pathophysiological role and therapeutic potential of the Renin-Angiotensin System (RAS) molecules for the control of proteinuria and for delaying the onset of CKD in patients with INS. This is a narrative review in which the databases PubMed, Web of Science, and Sci- ELO were searched for articles about INS and RAS. We selected articles that evaluated the pathophysiological role of RAS and the effects of the alternative RAS axis as a potential therapy for INS. Several studies using rodent models of nephropathies showed that the treatment with activators of the Angiotensin-Converting Enzyme 2 (ACE2) and with Mas receptor agonists reduces proteinuria and improves kidney tissue damage. Another recent paper showed that the reduction of urinary ACE2 levels in children with INS correlates with proteinuria and higher concentrations of inflammatory cytokines, although data with pediatric patients are still limited. The molecules of the alternative RAS axis comprise a wide spectrum, not yet fully explored, of potential pharmacological targets for kidney diseases. The effects of ACE2 activators and receptor Mas agonists show promising results that can be useful for nephropathies including INS.

According to the World Health Organization (WHO), epilepsy is the 4th most prevalent neurological disorder after migraine, stroke, and Alzheimer’s disease. There are numerous types of epileptic syndrome that are reported in children; one of them is Dravet syndrome. It is a neurological disorder of infants’ outset during the first year of life. Dravet syndrome is a genetically determined syndrome and the most studied form of genetic epilepsy. Nearly 70-80% of its cases are due to genetic alterations in the SCN1A gene, and almost 16% of cases are due to variations in the PCDH19 gene. Besides that, mutations in SCN1B, SCN2A, and GABRG2, including some novel genes, STXBP1, HCN1, and CDH2 have been observed in DS patients. It is a drug-resistant epileptic syndrome and its complete removal is still challenging. So, novel therapeutic techniques are being used to treat drug-resistant seizures. Recently, new strategies have been made to improve the neuron-specific targeting of AEDs encapsulated by nanocarriers. The nanocarriers will have a major contribution to nano-neuro medicines such as drug delivery, neuroimaging, neuroprotection, neurosurgery, and neuroregeneration. The nanotechnology-mediated techniques also have a fantastic success rate in gene therapy, as reported in recent years. The anti- epileptic drug delivery with the help of nanoparticles, at the targeted position, makes them applicable for the possible treatment of drug-resistant seizures and gives new hope to patients affected with it.

COVID-19 is caused by the SARS-CoV-2 virus, which has afflicted more than 245.37 million individuals worldwide and resulted in more than 4.9 million deaths as of today, with a mortality rate of 2.1%. Diabetes mellitus (DM) and its secondary complications are the major serious global health concerns today due to its growth rate, and it is the fastest-growing non-communicable disease. According to International Diabetes Federation (IDF) data, one out of 11 adults is diabetic, and the projection says that the figure will reach 642 million by 2040 globally. The occurrence of DM and its secondary complications is also associated with the severity of COVID-19 and high mortality. People with DM have a weakened immune system owing to innate immunity defects affecting phagocytosis, neutrophil chemotaxis, and cellmediated immunity; however, the high prevalence of diabetes in serious cases of COVID-19 may reflect the higher prevalence of type 2 DM (T2DM) in older people. Moreover, DM is linked to cardiovascular illness in older people, which could underlie the correlation between COVID-19 and fatal outcomes. SARS-CoV-2 infects via the angiotensin-converting enzyme 2 (ACE2), which is found in pancreatic islets, and infection with SARS-CoV-1 has been linked to hyperglycemia in individuals who do not have DM. And hence diabetic patients need to take more precautions and maintain their blood glucose levels. Many pieces of research say that COVID-19 and DM, especially its secondary complications are interlinked. But it also needs more elaborative evidence on whether the anti-diabetic drugs can manage only blood glucose or SARS-CoV-2.

Modafinil (MOD, 2128;diphenyl128;methyl128;sulphinil128;2128;acetamide) is a stimulant-like medicine used to treat narcolepsy. Off-label uses include improving cognitive ability in the course of other diseases. This review aims to discuss findings demonstrating the memory and learningenhancing activity of MOD in experimental and clinical studies. We included behavioral evaluations alongside the effects of MOD at the cellular and molecular level. MOD in different animal disease models exerted beneficial effects on induced memory and learning impairment, which in some cases were accompanied by modulation of neurotransmitter pathways or neuroplastic capabilities, reducing oxidative stress, or expression of synaptic proteins. Individuals treated with MOD showed improved memory and learning skills in different conditions. These effects were associated with regulating brain activity in some participants, confirmed by functional magnetic resonance imaging. Presented herein, data support the use of MOD in treating memory and learning deficits in various disease conditions.