Effect of Apis mellifera syriaca Bee Venom on Glioblastoma Cancer: In Vitro and In Vivo Studies.

Glioblastoma multiforme (GBM) is a highly aggressive and fatal primary brain tumor. The resistance of GBM to conventional treatments is attributed to factors such as the blood-brain barrier, tumor heterogeneity, and treatment-resistant stem cells. Current therapeutic efforts show limited survival benefits, emphasizing the urgent need for novel treatments. In this context, natural anti-cancer extracts and especially animal venoms have garnered attention for their potential therapeutic benefits. Bee venom in general and that of the Middle Eastern bee, Apis mellifera syriaca in particular, has been shown to have cytotoxic effects on various cancer cell types, but not glioblastoma. Therefore, this study aimed to explore the potential of A. mellifera syriaca venom as a selective anti-cancer agent for glioblastoma through in vitro and in vivo studies. Our results revealed a strong cytotoxic effect of A. mellifera syriaca venom on U87 glioblastoma cells, with an IC50 of 14.32 µg/mL using the MTT test and an IC50 of 7.49 µg/mL using the LDH test. Cells treated with the bee venom became permeable to propidium iodide without showing any signs of early apoptosis, suggesting compromised membrane integrity but not early apoptosis. In these cells, poly (ADP-ribose) polymerase (PARP) underwent proteolytic cleavage similar to that seen in necrosis. Subsequent in vivo investigations demonstrated a significant reduction in the number of U87 cells in mice following bee venom injection, accompanied by a significant increase in cells expressing caspase-3, suggesting the occurrence of cellular apoptosis. These findings highlight the potential of A. mellifera syriaca venom as a therapeutically useful tool in the search for new drug candidates against glioblastoma and give insights into the molecular mechanism through which the venom acts on cancer cells.

Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.

Antimicrobial resistance (AMR) poses a serious global health concern, resulting in a significant number of deaths annually due to infections that are resistant to treatment. Amidst this crisis, antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics (ATBs). These cationic peptides, naturally produced by all kingdoms of life, play a crucial role in the innate immune system of multicellular organisms and in bacterial interspecies competition by exhibiting broad-spectrum activity against bacteria, fungi, viruses, and parasites. AMPs target bacterial pathogens through multiple mechanisms, most importantly by disrupting their membranes, leading to cell lysis. However, bacterial resistance to host AMPs has emerged due to a slow co-evolutionary process between microorganisms and their hosts. Alarmingly, the development of resistance to last-resort AMPs in the treatment of MDR infections, such as colistin, is attributed to the misuse of this peptide and the high rate of horizontal genetic transfer of the corresponding resistance genes. AMP-resistant bacteria employ diverse mechanisms, including but not limited to proteolytic degradation, extracellular trapping and inactivation, active efflux, as well as complex modifications in bacterial cell wall and membrane structures. This review comprehensively examines all constitutive and inducible molecular resistance mechanisms to AMPs supported by experimental evidence described to date in bacterial pathogens. We also explore the specificity of these mechanisms toward structurally diverse AMPs to broaden and enhance their potential in developing and applying them as therapeutics for MDR bacteria. Additionally, we provide insights into the significance of AMP resistance within the context of host-pathogen interactions.

Neuroarchitecture: How the Perception of Our Surroundings Impacts the Brain.

The study of neuroarchitecture is concerned with the significant effects of architecture on human behavior, emotions and thought processes. This review explores the intricate relationship between the brain and perceived environments, focusing on the roles of the anterior cingulate cortex (ACC) and parahippocampal place area (PPA) in processing architectural stimuli. It highlights the importance of mirror neurons in generating empathetic responses to our surroundings and discusses how architectural elements like lighting, color, and space layout significantly impact emotional and cognitive experiences. The review also presents insights into the concept of cognitive maps and spatial navigation, emphasizing the role of architecture in facilitating wayfinding and orientation. Additionally, it addresses how neuroarchitecture can be applied to enhance learning and healing environments, drawing upon principles from the Reggio Emilia approach and considerations for designing spaces for the elderly and those with cognitive impairments. Overall, this review offers a neuroscientific basis for understanding how human cognition, emotions, spatial navigation, and well-being are influenced by architectural design.

Report from the 29th Meeting on Toxinology, "Toxins: From the Wild to the Lab", Organized by the French Society of Toxinology on 30 November-1 December 2023.

The French Society of Toxinology (SFET), which celebrated its 30th anniversary this year, organized its 29th annual Meeting (RT29), shared by 87 participants, on 30 November-1 December 2023. The RT29 main theme, "Toxins: From the Wild to the Lab", focused on research in the field of animal venoms and animal, bacterial, fungal, or plant toxins, from their discovery in nature to their study in the laboratory. The exploration of the functions of toxins, their structures, their molecular or cellular ligands, their mode of action, and their potential therapeutic applications were emphasized during oral communications and posters through three sessions, of which each was dedicated to a secondary theme. A fourth, "miscellaneous" session allowed participants to present recent out-of-theme works. The abstracts of nine invited and 15 selected lectures, those of 24 posters, and the names of the Best Oral Communication and Best Poster awardees, are presented in this report.

Treating COVID-19 with Medicinal Plants: Is It Even Conceivable? A Comprehensive Review.

In 2020, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) challenged the world with a global outbreak that led to millions of deaths worldwide. Coronavirus disease 2019 (COVID-19) is the symptomatic manifestation of this virus, which can range from flu-like symptoms to utter clinical complications and even death. Since there was no clear medicine that could tackle this infection or lower its complications with minimal adverse effects on the patients' health, the world health organization (WHO) developed awareness programs to lower the infection rate and limit the fast spread of this virus. Although vaccines have been developed as preventative tools, people still prefer going back to traditional herbal medicine, which provides remarkable health benefits that can either prevent the viral infection or limit the progression of severe symptoms through different mechanistic pathways with relatively insignificant side effects. This comprehensive review provides scientific evidence elucidating the effect of 10 different plants against SARS-CoV-2, paving the way for further studies to reconsider plant-based extracts, rich in bioactive compounds, into more advanced clinical assessments in order to identify their impact on patients suffering from COVID-19.

Engineering innovations in medicine and biology: Revolutionizing patient care through mechanical solutions.

The overlap between mechanical engineering and medicine is expanding more and more over the years. Engineers are now using their expertise to design and create functional biomaterials and are continually collaborating with physicians to improve patient health. In this review, we explore the state of scientific knowledge in the areas of biomaterials, biomechanics, nanomechanics, and computational fluid dynamics (CFD) in relation to the pharmaceutical and medical industry. Focusing on current research and breakthroughs, we provide an overview of how these fields are being used to create new technologies for medical treatments of human patients. Barriers and constraints in these fields, as well as ways to overcome them, are also described in this review. Finally, the potential for future advances in biomaterials to fundamentally change the current approach to medicine and biology is also discussed.

Apis mellifera syriaca Venom Modulates Splenic Cytokines Levels in BALB/c Mice.

Bee venoms are well-known for their important biological activities. More specifically, the venom of Apis mellifera syriaca was shown to exhibit various biological effects, including antimicrobial effects. It is suggested that the anti-microbial effect of venom could be accompanied by an immunomodulatory response in the host favoring anti-inflammatory responses. Thus, in this work, we investigated, for the first time, the immunomodulatory effects of A. mellifera syriaca venom in mice. Firstly, it was found that this venom exhibited mild toxicity in BALB/c mice after intraperitoneal injection with an LD50 of 3.8 mg/kg. We then investigated its immunomodulatory effects by evaluating the splenic levels of both pro- and anti-inflammatory cytokines in mice by ELISA. Interestingly, at 1 mg/kg, A. mellifera syriaca venom induced a decrease in IFN-γ, TNF-α, IL-4, and IL-10 at 24h postinjection. At a higher dose (3 mg/kg), an increase in IFN-γ and IL-4 levels was observed, while the levels of TNF-α and IL-10 remained low compared to the control. Altogether, these preliminary data suggest that A. mellifera syriaca venom exhibits anti-inflammatory effects at a sublethal dose (1 mg/kg), while at a higher dose (3 mg/kg), it induces inflammatory effects.

Bee Venom and Its Two Main Components-Melittin and Phospholipase A2-As Promising Antiviral Drug Candidates.

Viruses are known to infect most types of organisms. In humans, they can cause several diseases that range from mild to severe. Although many antiviral therapies have been developed, viral infections continue to be a leading cause of morbidity and mortality worldwide. Therefore, the discovery of new and effective antiviral agents is desperately needed. Animal venoms are a rich source of bioactive molecules found in natural goods that have been used since ancient times in alternative medicine to treat a variety of human diseases. Recently, and with the onset of the COVID-19 pandemic, scientists have regained their interest in the possible use of natural products, such as bee venom (BV), as a potential antiviral agent to treat viral infections. BV is known to exert many therapeutic activities such as anti-proliferative, anti-bacterial, and anti-inflammatory effects. However, there is limited discussion of the antiviral activity of BV in the literature. Therefore, this review aims to highlight the antiviral properties of BV and its two primary constituents, melittin (MEL) and phospholipase A2 (PLA2), against a variety of enveloped and non-enveloped viruses. Finally, the innovative strategies used to reduce the toxicity of BV and its two compounds for the development of new antiviral treatments are also considered.

Unlocking the Benefits of Fasting: A Review of Its Impact on Various Biological Systems and Human Health.

Fasting has gained significant attention in recent years for its potential health benefits in various body systems. This review aims to comprehensively examine the effects of fasting on human health, specifically focusing on its impact on different body's physiological systems. The cardiovascular system plays a vital role in maintaining overall health, and fasting has shown promising effects in improving cardiovascular health markers such as blood pressure, cholesterol levels, and triglyceride levels. Additionally, fasting has been suggested to enhance insulin sensitivity, promote weight loss, and improve metabolic health, thus offering potential benefits to individuals with diabetes and metabolic disorders. Furthermore, fasting can boost immune function, reduce inflammation, enhance autophagy, and support the body's defense against infections, cancer, and autoimmune diseases. Fasting has also demonstrated a positive effect on the brain and nervous system. It has been associated with neuroprotective properties, improving cognitive function, and reducing the risk of neurodegenerative diseases, besides the ability of increasing the lifespan. Hence, understanding the potential advantages of fasting can provide valuable insights for individuals and healthcare professionals alike in promoting health and wellbeing. The data presented here may have significant implications for the development of therapeutic approaches and interventions using fasting as a potential preventive and therapeutic strategy.

Scorpion Venom as a Source of Antimicrobial Peptides: Overview of Biomolecule Separation, Analysis and Characterization Methods.

Scorpion venoms have long captivated scientific researchers, primarily due to the potency and specificity of the mechanism of action of their derived components. Among other molecules, these venoms contain highly active compounds, including antimicrobial peptides (AMPs) and ion channel-specific components that selectively target biological receptors with remarkable affinity. Some of these receptors have emerged as prime therapeutic targets for addressing various human pathologies, including cancer and infectious diseases, and have served as models for designing novel drugs. Consequently, extensive biochemical and proteomic investigations have focused on characterizing scorpion venoms. This review provides a comprehensive overview of the key methodologies used in the extraction, purification, analysis, and characterization of AMPs and other bioactive molecules present in scorpion venoms. Noteworthy techniques such as gel electrophoresis, reverse-phase high-performance liquid chromatography, size exclusion chromatography, and "omics" approaches are explored, along with various combinations of methods that enable bioassay-guided venom fractionation. Furthermore, this review presents four adapted proteomic workflows that lead to the comprehensive dissection of the scorpion venom proteome, with an emphasis on AMPs. These workflows differ based on whether the venom is pre-fractionated using separation techniques or is proteolytically digested directly before further proteomic analyses. Since the composition and functionality of scorpion venoms are species-specific, the selection and sequence of the techniques for venom analyses, including these workflows, should be tailored to the specific parameters of the study.

2C protein of Enterovirus: key protein of viral replication and antiviral target.

Enteroviruses (EVs) include many human pathogens of increasing public health concern. These EVs are often associated with mild clinical manifestations, but they can lead to serious complications such as encephalitis, meningitis, pneumonia, myocarditis or poliomyelitis. Despite significant advances, there is no approved antiviral therapy for the treatment of enterovirus infections. Due to the high genotypic diversity of EVs, molecules targeting highly conserved viral proteins may be considered for developing a pan-EV treatment. In this regard, the ATPase/Helicase 2C, which is a highly conserved non-structural protein among EVs, has essential functions for viral replication and is therefore an attractive antiviral target. Recent functional and structural studies on the 2C protein led to the identification of molecules showing ex vivo anti-EV activity and associated with resistance mutations on the coding sequence of the 2C protein. This review presents the current state of knowledge about the 2C protein from an antiviral target perspective and the mode of action of specific inhibitors for this therapeutic target.