Regulation of stressed-induced cell death by the Bcl-2 family of apoptotic proteins.

Apoptosis is often deregulated in a number of human diseases. Heat-induced apoptosis is a model system for studying the consequences of protein misfolding and is mediated by the Bcl-2 family of proteins. This family consists of both pro-apoptotic and anti-apoptotic members that control mitochondrial integrity. The BH3-only pro-apoptotic members are strong inducers of apoptotic cell death. Protein damaging stress can activate a process of cellular destruction known as apoptosis. The pro-apoptotic BH3-only proteins and transcription factors activate this death pathway by inhibiting the anti-apoptotic Bcl-2 family proteins eliminating cancer cells in a short period of time.

Heat shock inhibition of CDK5 increases NOXA levels through miR-23a repression.

Hyperthermia is a proteotoxic stress that is lethal when exposure is extreme but also cytoprotective in that sublethal exposure leads to the synthesis of heat shock proteins, including HSP70, which are able to inhibit stress-induced apoptosis. CDK5 is an atypical cyclin-dependent kinase family member that regulates many cellular functions including motility and survival. Here we show that exposure of a human lymphoid cell line to hyperthermia causes CDK5 insolubilization and loss of tyrosine-15 phosphorylation, both of which were prevented in cells overexpressing HSP70. Inhibition of CDK5 activity with roscovitine-sensitized cells to heat induced apoptosis indicating a protective role for CDK5 in inhibiting heat-induced apoptosis. Both roscovitine and heat shock treatment caused increased accumulation of NOXA a pro-apoptotic BH3-only member of the BCL2 family. The increased abundance of NOXA by CDK5 inhibition was not a result of changes in NOXA protein turnover. Instead, CDK5 inhibition increased NOXA mRNA and protein levels by decreasing the expression of miR-23a, whereas overexpressing the CDK5 activator p35 attenuated both of these effects on NOXA and miR-23a expression. Lastly, overexpression of miR-23a prevented apoptosis under conditions in which CDK5 activity was inhibited. These results demonstrate that CDK5 activity provides resistance to heat-induced apoptosis through the expression of miR-23a and subsequent suppression of NOXA synthesis. Additionally, they indicate that hyperthermia induces apoptosis through the insolubilization and inhibition of CDK5 activity.

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.

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.

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.

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.

Exploring Gel-Point Identification in Epoxy Resin Using Rheology and Unsupervised Learning.

Any thermoset resin's processing properties and end-use performance are heavily influenced by the gel time. The complicated viscosity of resin as a function of temperature is investigated in this work, with a particular emphasis on identifying the gel point and comprehending polymerization. Rheology studies carried out using a plate-plate controlled stress rheometer under isothermal conditions were used to compare three experimental techniques for figuring out an epoxy resin's gel point. We also look at the basic modifications that take place during polymerization. We verify the reliability of the three strategies by including Principal Component Analysis (PCA), an unsupervised machine learning methodology. PCA assists in uncovering hidden connections between these methods and various affecting factors. PCA serves a dual role in our study, confirming method validity and identifying patterns. It sheds light on the intricate relationships between experimental techniques and material properties. This concise study expands our understanding of resin behavior and provides insights that are essential for optimizing resin-based processes in a variety of industrial applications.

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.

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.

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.

The Role of Vaccination and Face Mask Wearing on COVID-19 Infection and Hospitalization: A Cross-Sectional Study of the MENA Region.

Since the emergence of the Coronavirus disease (COVID-19) pandemic, the disease has affected more than 675 million people worldwide, including more than 6.87 million deaths. To mitigate the effects of this pandemic, many countries established control measures to contain its spread. Their riposte was based on a combination of pharmaceutical (vaccination) and non-pharmaceutical (such as facemask wearing, social distancing, and quarantine) measures. In this way, cross-sectional research was conducted in Algeria from 23 December 2021 to 12 March 2022 to investigate the effectiveness of preventative interventions in lowering COVID-19 infection and severity. More specifically, we investigated the link between mask-wearing and infection on one side, and the relationship between vaccination and the risk of hospitalization on the other. For this purpose, we used binary logistic regression modeling that allows learning the role of mask-wearing and vaccination in a heterogeneous society with respect to compliance with barrier measures. This study determined that wearing a mask is equally important for people of all ages. Further, findings revealed that the risk of infection was 0.79 times lower among those who were using masks (odds ratio (OR) = 0.79; confidence interval (CI) 95% = 0.668-0.936; p-value = 0.006). At the same time, vaccination is a necessary preventive measure as the risk of hospitalization increases with age. Compared with those who did not get vaccinated, those who got vaccinated were 0.429 times less likely to end up in the hospital (OR = 0.429; CI95% = 0.273-0.676; p < 0.0001). The model performance demonstrates significant relationships between the dependent and independent variables, with the absence of over-dispersion in both studied models, such as the Akaike Information Criterion (AIC) scores. These findings emphasize the significance of preventative measures and immunization in the battle against the COVID-19 pandemic.

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.

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.

The Importance of Behavioral and Native Factors on COVID-19 Infection and Severity: Insights from a Preliminary Cross-Sectional Study.

The COVID-19 pandemic has had a major impact on a global scale. Understanding the innate and lifestyle-related factors influencing the rate and severity of COVID-19 is important for making evidence-based recommendations. This cross-sectional study aims at establishing a potential relationship between human characteristics and vulnerability/resistance to SARS-CoV-2. We hypothesize that the impact of the virus is not the same due to cultural and ethnic differences. A cross-sectional study was performed using an online questionnaire. The methodology included the development of a multi-language survey, expert evaluation, and data analysis. Data were collected using a 13-item pre-tested questionnaire based on a literature review between 9 December 2020 and 21 July 2021. Data were statistically analyzed using logistic regression. For a total of 1125 respondents, 332 (29.5%) were COVID-19 positive; among them, 130 (11.5%) required home-based treatment, and 14 (1.2%) intensive care. The significant and most influential factors on infection included age, physical activity, and health status (p < 0.05), i.e., better physical activity and better health status significantly reduced the possibility of infection, while older age significantly increased it. The severity of infection was negatively associated with the acceptance (adherence and respect) of preventive measures and positively associated with tobacco (p < 0.05), i.e., smoking regularly significantly increases the severity of COVID-19 infection. This suggests the importance of behavioral factors compared to innate ones. Apparently, individual behavior is mainly responsible for the spread of the virus. Therefore, adopting a healthy lifestyle and scrupulously observing preventive measures, including vaccination, would greatly limit the probability of infection and prevent the development of severe COVID-19.

The Role of Retinoblastoma Protein in Cell Cycle Regulation: An Updated Review.

Selected transcription factors have critical roles to play in organism survival by regulating the expression of genes that control the adaptations needed to handle stress conditions. The retinoblastoma (Rb) protein coupled with the E2F transcription factor family was demonstrated to have roles in controlling the cell cycle during freezing and associated environmental stresses (anoxia, dehydration). Rb phosphorylation or acetylation at different sites provides a mechanism for repressing cell proliferation that is under the control of E2F transcription factors in animals facing stresses that disrupt cellular energetics or cell volume controls. Other central regulators of the cell cycle including Cyclins, Cyclin-dependent kinases (Cdks), and checkpoint proteins detect DNA damage or any improper replication, blocking further progression of cell cycle and interrupting cell proliferation. This review provides an insight into the molecular regulatory mechanisms of cell cycle control, focusing on Rb-E2F along with Cyclin-Cdk complexes typically involved in development and differentiation that need to be regulated in order to survive extreme cellular stress.

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.

MicroRNAs: Crucial Regulators of Stress.

BACKGROUND: Signaling pathways including gene silencing, cellular differentiation, homeostasis, development and apoptosis are regulated and controlled by a wide range of miRNAs. OBJECTIVE: Due to their potential binding sites in human-protein coding genes, many studies have also linked their altered expressions in various cancer types making them tumor suppressors agents. METHODS: Moreover, each miRNA is predicted to have many mRNA targets indicating their extensive regulatory role in cell survival and developmental processes. Nowadays, diagnosis of early cancer stage development is now dependent on variable miRNA expression levels as potential oncogenic biomarkers in validating and targeting microRNAs for cancer therapy. RESULTS: As the majority of miRNA, transcripts are derived from RNA polymerase II-directed transcription, stress response could result on a general reduction in the abundance of these transcripts. Over expression of various microRNAs have lead to B cell malignancy, potentiated KrasG12Dinduced lung tumorigenesis, chronic lymphocytic leukemia, lymphoproliferative disease and autoimmunity. CONCLUSION: Altered miRNA expressions could have a significant impact on the abundance of proteins, making them attractive candidates as biomarkers for cancer detection and important regulators of apoptosis.

Examination of the Role of miR-23a in the Development of Thermotolerance.

BACKGROUND: Thermotolerance is an acquired state of increased heat resistance that occurs following exposure to non-lethal proteotoxic stress. A large body of evidences implicates that molecular chaperon members belonging to the heat shock protein family could be acting as potential mediators of the thermotolerant state. OBJECTIVE: Recent evidence has demonstrated heat shock proteins HSP90, HSP70 and HSP27 have inhibited heat-induced cell death by intervening at various steps in stressinduced apoptotic pathways. Previous studies have shown that HSP70 prevented heatinduced apoptosis by preventing the NOXA dependent decrease in MCL-1 levels leading to both BAX activation and cytochrome c release from mitochondria. We have also demonstrated that HSP70 expressing cells have enhanced levels of miR-23a prevent heat-induced increase in NOXA levels and suppress apoptosis. METHODS: Stably transfected cell lines expressing either a control shRNA or a miR-23a targeting shRNA are quantified using both RT-PCR and semi-quantitative RT-PCR to determine the effect of different hyperthermic exposure treatment on miR-23a and Noxa mRNA expression levels. RESULTS: This study shows that thermotolerant-induced pre-heat shock treatment is capable of increasing miR-23a levels. Furthermore, stable cell clones expressing a miR- 23a targeting shRNA having reduced miR-23a levels are incapable of developing a thermotolerance state, leading to apoptosis. CONCLUSION: These results demonstrate the novel finding that miR-23a is an important factor in the development of the thermotolerant state.

CDK5: Key Regulator of Apoptosis and Cell Survival.

The atypical cyclin-dependent kinase 5 (CDK5) is considered as a neuron-specific kinase that plays important roles in many cellular functions including cell motility and survival. The activation of CDK5 is dependent on interaction with its activator p35, p39, or p25. These activators share a CDK5-binding domain and form a tertiary structure similar to that of cyclins. Upon activation, CDK5/p35 complexes localize primarily in the plasma membrane, cytosol, and perinuclear region. Although other CDKs are activated by cyclins, binding of cyclin D and E showed no effect on CDK5 activation. However, it has been shown that CDK5 can be activated by cyclin I, which results in anti-apoptotic functions due to the increased expression of Bcl-2 family proteins. Treatment with the CDK5 inhibitor roscovitine sensitizes cells to heat-induced apoptosis and its phosphorylation, which results in prevention of the apoptotic protein functions. Here, we highlight the regulatory mechanisms of CDK5 and its roles in cellular processes such as gene regulation, cell survival, and apoptosis.