Cannabinoids and Multiple Sclerosis: A Critical Analysis of Therapeutic Potentials and Safety Concerns

Multiple sclerosis (MS) is a complicated condition in which the immune system attacks myelinated axons in the central nervous system (CNS), destroying both myelin and axons to varying degrees. Several environmental, genetic, and epigenetic factors influence the risk of developing the disease and how well it responds to treatment. Cannabinoids have recently sparked renewed interest in their therapeutic applications, with growing evidence for their role in symptom control in MS. Cannabinoids exert their roles through the endogenous cannabinoid (ECB) system, with some reports shedding light on the molecular biology of this system and lending credence to some anecdotal medical claims. The double nature of cannabinoids, which cause both positive and negative effects, comes from their actions on the same receptor. Several mechanisms have been adopted to evade this effect. However, there are still numerous limitations to using cannabinoids to treat MS patients. In this review, we will explore and discuss the molecular effect of cannabinoids on the ECB system, the various factors that affect the response to cannabinoids in the body, including the role of gene polymorphism and its relation to dosage, assessing the positive over the adverse effects of cannabinoids in MS, and finally, exploring the possible functional mechanism of cannabinoids in MS and the current and future progress of cannabinoid therapeutics

A Novel Electrochemical Differentiation between Exosomal-RNA of Breast Cancer MCF7 and MCF7/ADR-Resistant Cells

Cancer is considered one of the most burdensome diseases affecting lives and, hence, the economy. Breast cancer is one of the most common types of cancer. Patients with breast cancer are divided into two groups: one group responds to the chemotherapy, and the other group resists the chemotherapy. Unfortunately, the group which resists the chemotherapy is still suffering the pain associated with the severe side effects of the chemotherapy. Therefore, there is a critical need for a method to differentiate between both groups before the administration of the chemotherapy. Exosomes, the recently discovered nano-vesicles, are often used as cancer diagnostic biomarkers as their unique composition allows them to represent their parental cells, which makes them promising indicators for tumor prognosis. Exosomes contain proteins, lipids, and RNA that exist in most body fluids and are expelled by multiple cell types, including cancer cells. Furthermore, exosomal RNA has been significantly used as a promising biomarker for tumor prognosis. Herein, we have developed an electrochemical system that could successfully differentiate between MCF7 and MCF7/ADR depending on the exosomal RNA. The high sensitivity of the proposed electrochemical assay opens the door for further investigation that will address the other type of cancer cells

Mercury and Alzheimer’s disease: a look at the links and evidence

This review paper investigates a specific environmental-disease interaction between mercury exposure and Alzheimer’s disease hallmarks. Alzheimer’s disease is a neurodegenerative disorder affecting predominantly the memory of the affected individual. It prevails mostly in the elderly, rendering many factors as possible causative agents, which potentially contribute to the disease pathogenicity cumulatively. Alzheimer’s disease affects nearly 50 million people worldwide and is considered one the most devastating diseases not only for the patient but also for their families and caregivers. Mercury is a common environmental toxin, found in the atmosphere mostly due to human activity, such as coal-burning for heating and cooking. The natural release of mercury into the atmosphere occurs by volcanic eruptions, in the form of vapor, or weathering rocks. The most toxic form of mercury to humans is methylmercury, to which humans are exposed by the ingestion of fish. Methylmercury was found to exert its toxic effects on different parts of the human body, with predominance on the brain. There is no safe concentration for mercury in the atmosphere, even trace amounts can elicit harm to humans in the long term. Mercury’s effect on Alzheimer\u27s disease hallmarks formation, extracellular senile plaques, and intracellular neurofibrillary tangles, has been widely studied. This review demonstrates the involvement of mercury, in its different forms, in the pathway of amyloid-beta deposition and tau tangles formation. It aims to understand the link between mercury exposure and Alzheimer’s disease so that, in the future, prevention strategies can be applied to halt the progression of this disease

Coping with Water Stress: Ameliorative Effects of Combined Treatments of Salicylic Acid and Glycine Betaine on the Biometric Traits and Water-Use Efficiency of Onion (<i>Allium cepa</i>) Cultivated under Deficit Drip Irrigation

Freshwater scarcity is a major global challenge threatening food security. Agriculture requires huge quantities of water to feed the ever-increasing human population. Sustainable irrigation techniques such as deficit drip irrigation (DDI) are warranted to increase efficiency and maximize yield. However, DDI has been reported to cause water stress in plants. The study aimed to investigate the influence of the exogenous application of salicylic acid alone (SA) or in combination with glycine betaine (GB) on the growth, yield quality, and water-use efficiency of onions under different DDI treatments (100%, 70%, and 40% field capacity (FC)). Spray treatments (sub-treatments) were as follows: T1: (distilled water), T2: (1.09 mM SA), T3: (1.09 mM SA + 25 mM GB), T4: (1.09 mM SA + 50 mM GB), and T5: (1.09 mM SA + 100 mM GB). Our results indicated that T2 slightly ameliorated the effects of water stress by improved plant heights, leaf number, pseudostem diameter, bulb quality, and nutrient content of onion bulbs, especially under the 70% FC treatment. However, T3 recorded the poorest results on leaf number, pseudostem diameter, and bulb quality under the 70% and 40% FC treatments. Generally, our results indicated that onions could tolerate moderate water stress (70% FC) without severely affecting the growth and yield of onion. In conditions where freshwater is a limiting factor, a DDI treatment of 40% FC is recommended

The Anti-Inflammatory Properties of Phytochemicals and Their Effects on Epigenetic Mechanisms Involved in TLR4/NF-κB-Mediated Inflammation

Innate immune response induces positive inflammatory transducers and regulators in order to attack pathogens, while simultaneously negative signaling regulators are transcribed to maintain innate immune homeostasis and to avoid persistent inflammatory immune responses. The gene expression of many of these regulators is controlled by different epigenetic modifications. The remarkable impact of epigenetic changes in inducing or suppressing inflammatory signaling is being increasingly recognized. Several studies have highlighted the interplay of histone modification, DNA methylation, and post-transcriptional miRNA-mediated modifications in inflammatory diseases, and inflammation-mediated tumorigenesis. Targeting these epigenetic alterations affords the opportunity of attenuating different inflammatory dysregulations. In this regard, many studies have identified the significant anti-inflammatory properties of distinct naturally-derived phytochemicals, and revealed their regulatory capacity. In the current review, we demonstrate the signaling cascade during the immune response and the epigenetic modifications that take place during inflammation. Moreover, we also provide an updated overview of phytochemicals that target these mechanisms in macrophages and other experimental models, and go on to illustrate the effects of these phytochemicals in regulating epigenetic mechanisms and attenuating aberrant inflammation

Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma

Hepatocellular carcinoma is the fifth most common cancer worldwide and the second most lethal, following lung cancer. Currently applied therapeutic practices rely on surgical resection, chemotherapy and radiotherapy, or a combination thereof. These treatment options are associated with extreme adversities, and risk/benefit ratios do not always work in patients’ favor. Anomalies of the epigenome lie at the epicenter of aberrant molecular mechanisms by which the disease develops and progresses. Modulation of these anomalous events poses a promising prospect for alternative treatment options, with an abundance of felicitous results reported in recent years. Herein, the most recent epigenetic modulators in hepatocellular carcinoma are recapitulated on

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2

Sets of 3-alkenyl-2-oxindoles (6,10,13) were synthesized in a facile synthetic pathway through acid dehydration (EtOH/HCl) of the corresponding 3-hydroxy-2-oxoindolines (5,9,12). Single crystal (10a,c) and powder (12a,26f) X-ray studies supported the structures. Compounds 6c and 10b are the most effective agents synthesized (about 3.4, 3.3 folds, respectively) against PaCa2 (pancreatic) cancer cell line relative to the standard reference used (Sunitinib). Additionally, compound 10b reveals antiproliferative properties against MCF7 (breast) cancer cell with IC close to that of Sunitinib. CAM testing reveals that compounds 6 and 10 demonstrated qualitative and quantitative decreases in blood vessel count and diameter with efficacy comparable to that of Sunitinib, supporting their anti-angiogenic properties. Kinase inhibitory properties support their multi-targeted inhibitory activities against VEGFR-2 and c-kit in similar behavior to that of Sunitinib. Cell cycle analysis studies utilizing MCF7 exhibit that compound 6b arrests the cell cycle at G1/S phase while, 10b reveals accumulation of the tested cell at S phase. Compounds 6a and 10b reveal potent antiviral properties against SARS-CoV-2 with high selectivity index relative to the standards (hydroxychloroquine, chloroquine). Safe profile of the potent synthesized agents, against normal cells (VERO-E6, RPE1), support the possible development of better hits based on the attained observations

Mercury and Alzheimer’s disease: a look at the links and evidence

This review paper investigates a specific environmental-disease interaction between mercury exposure and Alzheimer’s disease hallmarks. Alzheimer’s disease is a neurodegenerative disorder affecting predominantly the memory of the affected individual. It prevails mostly in the elderly, rendering many factors as possible causative agents, which potentially contribute to the disease pathogenicity cumulatively. Alzheimer’s disease affects nearly 50 million people worldwide and is considered one the most devastating diseases not only for the patient, but also for their families and caregivers. Mercury is a common environmental toxin, found in the atmosphere mostly due to human activity, such as coal burning for heating and cooking. Natural release of mercury into the atmosphere occurs by volcanic eruptions, in the form of vapor, or weathering rocks. The most toxic form of mercury to humans is methylmercury, to which humans are exposed to by ingestion of fish. Methylmercury was found to exert its toxic effects on different parts of the human body, with predominance on the brain. There is no safe concentration for mercury in the atmosphere, even trace amounts can elicit harm to humans in the long term. Mercury’s effect on Alzheimer’s disease hallmarks formation, extracellular senile plaques and intracellular neurofibrillary tangles, has been widely studied. This review demonstrates the involvement of mercury, in its different forms, in the pathway of amyloid beta deposition and tau tangles formation. It aims to understand the link between mercury exposure and Alzheimer’s disease so that, in the future, prevention strategies can be applied to halt the progression of this disease

Terfezia boudieri and Terfezia claveryi inhibit the LPS/IFN-γ-mediated inflammation in RAW 264.7 macrophages through an Nrf2-independent mechanism

Abstract Desert truffles have been used as traditional treatments for numerous inflammatory disorders. However, the molecular mechanisms underlying their anti-inflammatory effects in RAW 264.7 macrophages have yet to be fully elucidated. The present study investigated the anti-inflammatory activities of two main desert truffles, Terfezia boudieri and T. claveryi, and the underlying mechanisms associated with their anti-inflammatory activities in RAW 264.7 macrophages stimulated with lipopolysaccharide/interferon-gamma (LPS/IFN-γ). Our results demonstrated that treatment with T. boudieri and T. claveryi extracts effectively suppressed the inflammatory response in LPS/IFN-γ-stimulated RAW 264.7 macrophages. Specifically, T. boudieri extract was found to reduce the production of nitric oxide and inhibit the expression of various pro-inflammatory markers, including inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor-α, and interleukin-6 (IL-6) at both the mRNA and protein levels. Similarly, T. claveryi extract exhibited comparable inhibitory effects, except for the expression of IL-6 and COX-2 at the protein level, where no significant effect was observed. Moreover, both studied extracts significantly downregulated the microRNA expression levels of miR-21, miR-146a, and miR-155, suggesting that T. boudieri and T. claveryi suppress the inflammatory response in LPS/IFN-γ-stimulated RAW 264.7 cells through an epigenetic mechanism. Furthermore, our study reveals a new mechanism for the anti-inflammatory properties of desert truffle extracts. We show for the first time that Terfezia extracts do not rely on the nuclear factor erythroid 2-related factor 2 pathway, previously linked to anti-inflammatory responses. This expands our understanding of natural product anti-inflammatory mechanisms and could have important implications for developing new therapies. To account for differences in truffle effects, extracts prepared were subjected to secondary metabolites profiling using UPLC-MS. UPLC-MS led to the annotation of 87 secondary metabolites belonging to various classes, including amino acids, carbohydrates, alkaloids, amides, fatty acids, sterols, and phenolic compounds. Therefore, these results indicate that T. boudieri and T. claveryi exhibit anti-inflammatory activities through suppressing multiple inflammatory mediators and cytokines and may be potential anti-inflammatory agents