The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.
The application of metallic nanoparticles (materials with size at least in one dimension ranging from 1 to 100 nm) as a new therapeutic tool will improve the diagnosis and treatment of diseases. The mitochondria could be a therapeutic target to treat pathologies whose origin lies in mitochondrial dysfunctions or whose progression is dependent on mitochondrial function. We aimed to study the subcellular distribution of 2–4 nm iron nanoparticles and its effect on mitochondrial DNA (mtDNA), mitochondrial function, and autophagy in colorectal cell lines (HT-29). Results showed that when cells were exposed to ultra-small iron nanoparticles, their subcellular fate was mainly mitochondria, affecting its respiratory and glycolytic parameters, inducing the migration of the cellular state towards quiescence, and promoting and triggering the autophagic process. These effects support the potential use of nanoparticles as therapeutic agents using mitochondria as a target for cancer and other treatments for mitochondria-dependent pathologies.
Alzheimer's is a chronic degenerative disease of the central nervous system considered the leading cause of dementia in the world. It is characterized by two etiopathological events related to oxidative stress: the aggregation of β-amyloid peptide and the formation of neurofibrillary tangles of hyperphosphorylated Tau protein in the brain. The incidence of this disease increases with age and has been associated with inadequate lifestyles. Some natural compounds have been shown to improve the hallmarks of the disease. However, despite its potential, there is no scientific evidence about Manuka honey (MH) in this regard. In the present work we evaluated the effect of MH on the toxicity induced by Aβ aggregation and Tau in a Caenorhabditis elegans model. Our results demonstrated that MH was able to improve indicators of oxidative stress and delayed Aβ-induced paralysis in the AD model CL4176 through HSP-16.2 and SKN-1/NRF2 pathways. Nevertheless, its sugar content impaired the indicators of locomotion (an indicator of tau neurotoxicity) in both the transgenic strain BR5706 and in the wild-type N2 worms.
Tagetes erecta is an edible flower deeply rooted in traditional Mexican culture. It holds a central role in the most popular and iconic Mexican celebration, “the Day of the Dead”. Furthermore, it is currently receiving interest as a potential therapeutic agent, motivated mainly by its polyphenol content. The present study aims to evaluate the biological activity of an extract synthesized from the petals of the edible flower T. erecta. This extract showed significant antioxidant scores measured by the most common in vitro methodologies (FRAP, ABTS, and DPPH), with values of 1475.3 μM trolox/g extr, 1950.3 μM trolox/g extr, and 977.7 μM trolox/g extr, respectively. In addition, up to 36 individual polyphenols were identified by chromatography. Regarding the biomedical aspects of the petal extract, it exhibited antitumoral activity against ovarian carcinoma cells evaluated by the MTS assay, revealing a lower value of IC50 compared to other flower extracts. For example, the extract from T. erecta reported an IC50 value half as low as an extract from Rosa × hybrida and six times lower than another extract from Tulbaghia violacea. This antitumoral effect of T. erecta arises from the induction of the apoptotic process; thus, incubating ovarian carcinoma cells with the petal extract increased the rate of apoptotic cells measured by flow cytometry. Moreover, the extract also demonstrated efficacy as a therapeutic agent against tauopathy, a feature of Alzheimer’s disease (AD) in the Caenorhabditis elegans experimental model. Treating worms with the experimental extract prevented disfunction in several motility parameters such as wavelength and swimming speed. Furthermore, the T. erecta petal extract prevented the release of Reactive Oxygen Species (ROS), which are associated with the progression of AD. Thus, treatment with the extract resulted in an approximate 20% reduction in ROS production. These findings suggest that these petals could serve as a suitable source of polyphenols for biomedical applications.
Gestational Diabetes Mellitus (GDM) is the most frequent pregnancy-related medical issue and presents significant risks to both maternal and foetal health, requiring monitoring and management during pregnancy. The prevalence of GDM has surged globally in recent years, mirroring the rise in diabetes and obesity rates. Estimated to affect from 5% to 25% of pregnancies, GDM impacts approximately 21 million live births annually, according to the International Diabetes Federation (IDF). However, consensus on diagnostic approaches remains elusive, with varying recommendations from international organizations, which makes the comparison between research complicated. Compounding concerns are the short-term and long-term complications stemming from GDM for mothers and offspring. Maternal outcomes include heightened cardiovascular risks and a notable 70% risk of developing Type 2 Diabetes Mellitus (T2DM) within a decade postpartum. Despite this, research into the metabolic profiles associated with a previous GDM predisposing women to T2D remains limited. While genetic biomarkers have been identified, indicating the multifaceted nature of GDM involving hormonal changes, insulin resistance, and impaired insulin secretion, there remains a dearth of exploration into the enduring health implications for both mothers and their children. Furthermore, offspring born to mothers with GDM have been shown to face an increased risk of obesity and metabolic syndrome during childhood and adolescence, with studies indicating a heightened risk ranging from 20% to 50%. This comprehensive review aims to critically assess the current landscape of Gestational Diabetes Mellitus (GDM) research, focusing on its prevalence, diagnostic challenges, and health impacts on mothers and offspring. By examining state-of-the-art knowledge and identifying key knowledge gaps in the scientific literature, this review aims to highlight the multifaceted factors that have hindered a deeper understanding of GDM and its long-term consequences. Ultimately, this scholarly exploration seeks to promote further investigation into this critical area, improving health outcomes for mothers and their children.