Fetal dose from proton pencil beam scanning craniospinal irradiation during pregnancy: a Monte Carlo study

Objective: We conducted a Monte Carlo study to comprehensively investigate the fetal dose resulting from proton pencil beam scanning (PBS) craniospinal irradiation (CSI) during pregnancy. Approach: The gestational-age dependent pregnant phantom series developed at the University of Florida (UF) were converted into DICOM-RT format (CT images and structures) and imported into a treatment planning system (TPS) (Eclipse v15.6) commissioned to a IBA PBS nozzle. A proton PBS CSI plan (prescribed dose: 36 Gy) was created on the phantoms. The TOPAS MC code was used to simulate the proton PBS CSI on the phantoms, for which MC beam properties at the nozzle exit (spot size, spot divergence, mean energy, and energy spread) were matched to IBA PBS nozzle beam measurement data. We calculated mean absorbed doses for 28 organs and tissues and whole body of the fetus at eight gestational ages (8, 10, 15, 20, 25, 30, 35, and 38 weeks). For contextual purposes, the fetal organ/tissue doses from the treatment planning CT scan of the mother’s head and torso were estimated using the National Cancer Institute dosimetry system for CT (NCICT, Version 3) considering a low-dose CT protocol (CTDIvol: 8.97 mGy). Main Results: The majority of the fetal organ/tissue doses from the proton PBS CSI treatment fell within a range of 3 to 6 mGy. The fetal organ/tissue doses for the 38-week phantom showed the largest variation with the doses ranging from 2.9 mGy (adrenals) to 8.2 mGy (eye lenses) while the smallest variation ranging from 3.2 mGy (oesophagus) to 4.4 mGy (brain) was observed for the doses for the 20-week phantom. The fetal whole-body dose ranged from 3.7 mGy (25 weeks) to 5.8 mGy (8 weeks). Most of the fetal doses from the planning CT scan fell within a range of 7 to 13 mGy, approximately 2-to-9 times lower than the fetal dose equivalents of the proton PBS CSI treatment (assuming a quality factor of 7). Significance: The fetal organ/tissue doses observed in the present work will be useful for one of the first clinically informative predictions on the magnitude of fetal dose during proton PBS CSI during pregnancy.

Plant Flavonoids in Mediterranean Species: A Focus on Flavonols as Protective Metabolites under Climate Stress

Flavonoids are specialized metabolites largely widespread in plants where they play numerous roles including defense and signaling under stress conditions. These compounds encompass several chemical subgroups such as flavonols which are one the most represented classes. The most studied flavonols are kaempferol, quercetin and myricetin to which research attributes antioxidative properties and a potential role in UV-defense through UV-screening mechanisms making them critical for plant adaptation to climate change. Despite the great interest in flavonol functions in the last decades, some functional aspects remain under debate. This review summarizes the importance of flavonoids in plant defense against climate stressors and as signal molecules with a focus on flavonols in Mediterranean plant species. The review emphasizes the relationship between flavonol location (at the organ, tissue and cellular scales) and their function as defense metabolites against climate-related stresses. It also provides evidence that biosynthesis of flavonols, or flavonoids as a whole, could be a crucial process allowing plants to adapt to climate change, especially in the Mediterranean area which is considered as one of the most sensitive regions to climate change over the globe.

A note on robotics and artificial intelligence in pharmacy

: Artificial intelligence and robotics are two of the hottest and most recent technologies to emerge from the world of science. There is tremendous potential for these technologies to solve a wide range of pharmaceutical problems, including the reduction of the enormous amounts of money and time invested in the drug discovery and development process, technical solutions related to the quality of drug products, and an increase in the demand for pharmaceuticals. Nanorobotics is a new subfield that has emerged from the field of robotics itself. This technique makes use of robots that are as small as nano- or micron-sized to diagnose diseases and deliver drugs to the targeted organ, tissue, or cell. These techniques, as well as their various applications in the pharmacy sector, are extensively discussed throughout this article. Internationally renowned pharmaceutical companies are collaborating with Artificial Intelligence behemoths in order to revolutionise the discovery and development process of potential drug molecules and to ensure the highest possible quality in their products.

MicroRNA as a Potential Biomarker and Treatment Strategy for Ischemia-Reperfusion Injury

Ischemia-reperfusion (I/R) injury is a progressive injury that aggravates the pathological state when the organ tissue restores blood supply after a certain period of ischemia, including the myocardial, brain, liver, kidney, and intestinal. With growing evidence that microRNAs (miRNAs) play an important role as posttranscription gene silencing mediators in many I/R injury, in this review, we highlight the microRNAs that are related to I/R injury and their regulatory molecular pathways. In addition, we discussed the potential role of miRNA as a biomarker and its role as a target in I/R injury treatment. Developing miRNAs are not without its challenges, but prudent design combined with existing clinical treatments will result in more effective therapies for I/R injury. This review is aimed at providing new research results obtained in this research field. It is hoped that new research on this topic will not only generate new insights into the pathophysiology of miRNA in I/R injury but also can provide a basis for the clinical application of miRNA in I/R.

Hypoxia and the Kynurenine Pathway: Implications and Therapeutic Prospects in Alzheimer’s Disease

Neurodegenerative diseases (NDs) like Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease predominantly pose a significant socioeconomic burden. Characterized by progressive neural dysfunction coupled with motor or intellectual impairment, the pathogenesis of ND may result from contributions of certain environmental and molecular factors. One such condition is hypoxia, characterized by reduced organ/tissue exposure to oxygen. Reduced oxygen supply often occurs during the pathogenesis of ND and the aging process. Despite the well-established relationship between these two conditions (i.e., hypoxia and ND), the underlying molecular events or mechanisms connecting hypoxia to ND remain ill-defined. However, the relatedness may stem from the protective or deleterious effects of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1α). The upregulation of HIF-1α occurs in the pathogenesis of most NDs. The dual function of HIF-1α in acting as a “killer factor” or a “protective factor” depends on the prevailing local cellular condition. The kynurenine pathway is a metabolic pathway involved in the oxidative breakdown of tryptophan. It is essential in neurotransmission and immune function and, like hypoxia, associated with ND. Thus, a good understanding of factors, including hypoxia (i.e., the biochemical implication of HIF-1α) and kynurenine pathway activation in NDs, focusing on Alzheimer’s disease could prove beneficial to new therapeutic approaches for this disease, thus the aim of this review.

A European pharmacotherapeutic agent Roflumilast exploring integrated preclinical and clinical evidences for SARS CoV-2 mediated inflammation to organ damage

COVID-19 has spread globally, affecting almost 160 million individuals. Elderly and pre-existing patients (such as diabetes, heart disease and asthma), seems more susceptible to serious illness with COVID-19. Roflumilast was licensed for usage in the European Union in July 2010 as a phosphodiesterase-4 (PDE4) inhibitor. Roflumilast has been shown to decrease bleomycin-induced lung fibrosis, lung hydroxyproline, right heart thickning in animal prophylactic. The current study reviewed existing data that the PDE-4 inhibitor protects not just renal tissues but also other major organ systems after COVID-19 infection by decreasing immune cell infiltration. These immune-balancing effects of roflumilast were related with a decrease in oxidative and inflammatory burden, caspase-3 suppression, and increased PKA/cAMP levels in renal and other organ tissue.

Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage.