BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis

Apoptosis is an evolutionarily conserved and tightly regulated cell death pathway. Physiological cell death is important for maintaining homeostasis and optimal biological conditions by continuous elimination of undesired or superfluous cells. The BH3-only pro-apoptotic members are strong inducers of apoptosis. The pro-apoptotic BH3-only protein Noxa activates multiple death pathways by inhibiting the anti-apoptotic Bcl-2 family protein, Mcl-1, and other protein members leading to Bax and Bak activation and MOMP. On the other hand, Puma is induced by p53-dependent and p53-independent apoptotic stimuli in several cancer cell lines. Moreover, this protein is involved in several physiological and pathological processes, such as immunity, cancer, and neurodegenerative diseases. Future heat shock research could disclose the effect of hyperthermia on both Noxa and BH3-only proteins. This suggests post-transcriptional mechanisms controlling the translation of both Puma and Noxa mRNA in heat-shocked cells. This study was also the chance to recapitulate the different reactional mechanisms investigated for caspases

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

International audienceViruses 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

Regulation of cell cycle components during exposure to anoxia or dehydration stress in the wood frog, Rana sylvatica

The wood frog (Rana sylvatica) exhibits a well-developed natural anoxia and dehydration tolerance. The degree of stress tolerance depends on numerous biochemical adaptations, including stress-induced hypometabolism that helps to preserve long-term viability by reducing ATP demand. We hypothesized that the mechanisms involved in cell cycle control could act to aid in the establishment of the hypometabolic state required for stress survival. Selected proteins involved in the proliferation of cells were evaluated using immunoblotting in liver and skeletal muscle of wood frogs comparing controls with animals subjected to either 24-hr anoxia exposure under a nitrogen gas atmosphere or dehydration to 40% of total body water lost (all at 5°C). Levels of cyclins (type A, B, D, and E) decreased significantly under both stresses in liver and skeletal muscle. Similar reductions were seen for Cyclin-dependant kinases (Cdk) types 2, 4, and 6 in both liver and skeletal muscle; however, an increase in the relative amount of phosphorylated inactive p-Cdk (Thr14/Tyr15) was observed in liver under both stresses. Levels of positive regulators of Cdk activity (Cdc25 type A and C) were significantly reduced in both tissues under both stresses, whereas negative regulators of Cdk activity (p16 INK4a and p27 KIP1) increased significantly in liver under both anoxia and dehydration stress (but not in muscle). This study provides the first report of differential regulation of cell cycle components in an anoxia and dehydration tolerant vertebrate, the wood frog, suggesting that cell cycle suppression is an active part of stress resistance and life extension in hypometabolic states

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

Inhibitors of ATP Synthase as New Antibacterial Candidates

ATP, the power of all cellular functions, is constantly used and produced by cells. The enzyme called ATP synthase is the energy factory in all cells, which produces ATP by adding inorganic phosphate (Pi) to ADP. It is found in the inner, thylakoid and plasma membranes of mitochondria, chloroplasts and bacteria, respectively. Bacterial ATP synthases have been the subject of multiple studies for decades, since they can be genetically manipulated. With the emergence of antibiotic resistance, many combinations of antibiotics with other compounds that enhance the effect of these antibiotics have been proposed as approaches to limit the spread of antibiotic-resistant bacteria. ATP synthase inhibitors, such as resveratrol, venturicidin A, bedaquiline, tomatidine, piceatannol, oligomycin A and N,N-dicyclohexylcarbodiimide were the starting point of these combinations. However, each of these inhibitors target ATP synthase differently, and their co-administration with antibiotics increases the susceptibility of pathogenic bacteria. After a brief description of the structure and function of ATP synthase, we aim in this review to highlight therapeutic applications of the major bacterial ATP synthase inhibitors, including animal’s venoms, and to emphasize their importance in decreasing the activity of this enzyme and subsequently eradicating resistant bacteria as ATP synthase is their source of energy

The Application of Principal Component Analysis (PCA) for the Optimization of the Conditions of Fabrication of Electrospun Nanofibrous Membrane for Desalination and Ion Removal

Nowadays, acquiring a water supply for urban and industrial uses is one of the greatest challenges facing humanity for ensuring sustainability. Membrane technology has been considered cost-effective, encompasses lower energy requirements, and at the same time, offers acceptable performance. Electrospun nanofibrous membranes (ENMs) are considered a novel and promising strategy for the production of membranes that could be applied in several treatment processes, especially desalination and ion removal. In this study, we apply an unsupervised machine-learning strategy, the so-called principal component analysis (PCA), for the purpose of seeking discrepancies and similarities between different ENMs. The main purpose was to investigate the influence of membrane fabrication conditions, characteristics, and process conditions in order to seek the relevance of the application of different electrospun nanofibrous membranes (ENMs). Membranes were majorly classified into single polymers/layers, from one side, and dual multiple layer ENMs, from another side. For both classes, variables related to membrane fabrication conditions were not separated from membrane characterization variables. This reveals that membranes’ characteristics not only depend on the chemical composition, but also on the fabrication conditions. On the other hand, the process conditions of ENM fabrication showed an extensive effect on membranes’ performance

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

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

Protective Role and Functional Engineering of Neuropeptides in Depression and Anxiety: An Overview

Behavioral disorders, such as anxiety and depression, are prevalent globally and touch children and adults on a regular basis. Therefore, it is critical to comprehend how these disorders are affected. It has been demonstrated that neuropeptides can influence behavior, emotional reactions, and behavioral disorders. This review highlights the majority of the findings demonstrating neuropeptides’ behavioral role and functional engineering in depression and anxiety. Gut–brain peptides, hypothalamic releasing hormone peptides, opioid peptides, and pituitary hormone peptides are the four major groups of neuropeptides discussed. Some neuropeptides appear to promote depression and anxiety-like symptoms, whereas others seem to reduce it, all depending on the receptors they are acting on and on the brain region they are localized in. The data supplied here are an excellent starting point for future therapy interventions aimed at treating anxiety and depression