Selective Killing of Cancer Cells by Ashwagandha Leaf Extract and Its Component Withanone Involves ROS Signaling

Ashwagandha is a popular Ayurvedic herb used in Indian traditional home medicine. It has been assigned a variety of health-promoting effects of which the mechanisms remain unknown. We previously reported the selective killing of cancer cells by leaf extract of Ashwagandha (i-Extract) and its purified component Withanone. In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing) of the cellular targets and gene pathways.Randomized ribozyme library was introduced into cancer cells prior to the treatment with i-Extract. Ribozymes were recovered from cells that survived the i-Extract treatment. Gene targets of the selected ribozymes (as predicted by database search) were analyzed by bioinformatics and pathway analyses. The targets were validated for their role in i-Extract induced selective killing of cancer cells by biochemical and molecular assays. Fifteen gene-targets were identified and were investigated for their role in specific cancer cell killing activity of i-Extract and its two major components (Withaferin A and Withanone) by undertaking the shRNA-mediated gene silencing approach. Bioinformatics on the selected gene-targets revealed the involvement of p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling. We examined the involvement of ROS-signaling components (ROS levels, DNA damage, mitochondrial structure and membrane potential) and demonstrate that the selective killing of cancer cells is mediated by induction of oxidative stress.Ashwagandha leaf extract and Withanone cause selective killing of cancer cells by induction of ROS-signaling and hence are potential reagents that could be recruited for ROS-mediated cancer chemotherapy

Neuromuscular disease genetics in under-represented populations: increasing data diversity

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses \u27solved\u27 or \u27possibly solved\u27 ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% \u27solved\u27 and ∼13% \u27possibly solved\u27 outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

Happiness around the world: A combined etic-emic approach across 63 countries.

What does it mean to be happy? The vast majority of cross-cultural studies on happiness have employed a Western-origin, or "WEIRD" measure of happiness that conceptualizes it as a self-centered (or "independent"), high-arousal emotion. However, research from Eastern cultures, particularly Japan, conceptualizes happiness as including an interpersonal aspect emphasizing harmony and connectedness to others. Following a combined emic-etic approach (Cheung, van de Vijver & Leong, 2011), we assessed the cross-cultural applicability of a measure of independent happiness developed in the US (Subjective Happiness Scale; Lyubomirsky & Lepper, 1999) and a measure of interdependent happiness developed in Japan (Interdependent Happiness Scale; Hitokoto & Uchida, 2015), with data from 63 countries representing 7 sociocultural regions. Results indicate that the schema of independent happiness was more coherent in more WEIRD countries. In contrast, the coherence of interdependent happiness was unrelated to a country's "WEIRD-ness." Reliabilities of both happiness measures were lowest in African and Middle Eastern countries, suggesting these two conceptualizations of happiness may not be globally comprehensive. Overall, while the two measures had many similar correlates and properties, the self-focused concept of independent happiness is "WEIRD-er" than interdependent happiness, suggesting cross-cultural researchers should attend to both conceptualizations

The Recent Development of Acoustic Sensors as Effective Chemical Detecting Tools for Biological Cells and Their Bioactivities

One of the most significant developed technologies is the use of acoustic waves to determine the chemical structures of biological tissues and their bioactivities. In addition, the use of new acoustic techniques for in vivo visualizing and imaging of animal and plant cellular chemical compositions could significantly help pave the way toward advanced analytical technologies. For instance, acoustic wave sensors (AWSs) based on quartz crystal microbalance (QCM) were used to identify the aromas of fermenting tea such as linalool, geraniol, and trans-2-hexenal. Therefore, this review focuses on the use of advanced acoustic technologies for tracking the composition changes in plant and animal tissues. In addition, a few key configurations of the AWS sensors and their different wave pattern applications in biomedical and microfluidic media progress are discussed

The Optimum Concentration of N-Methyl D-Aspartate to Induce Dorsal Root Ganglion Neuron Activation through the N-Methyl D-Aspartate Receptor Pathway: Creating a Neuron Model For the in-vitro Study of Pain

Background: In the in-vitro study on chronic pain, the N-methyl D-Aspartate receptor (NMDAR) activation in the dorsal root ganglion (DRG) neuron became one of the most important mechanisms to activate the chronic pain pathways. NMDAR activation can be induced using an NMDAR agonist. No guidelines explain the NMDA optimum concentration to induce DRG neuron activation through the NMDAR pathway. This study aims to find the optimum concentration of NMDA to induce DRG neuron activation through the NMDAR pathway. Materials and Methods: We treat DRG neuron culture derived from the F11 cell line with 10, 20, 40, 60, 80, and 100 µM NMDA. Phosphorylated extracellular signal-regulated kinase (pERK), an activated neuron biomarker, is measured using an immunocytochemistry assay as a neuron activation biomarker. We validate the NMDA optimum concentration by measuring intracellular Ca2+ level, mitochondrial membrane potential (Δψm), and cytosolic adenosine triphosphate (ATP) in the activated neuron. Those parameters are the downstream process following NMDAR activation and are related to neuron activity. Statistical analysis was performed using the One-Way ANOVA test with α=5%. Results: We found that NMDA 80 µM significantly had the highest pERK intensity and showed the most optimum neuron activation. Validation tests show an increase in intracellular Ca2+ influx and Δψm. NMDA 80 µM also causes significant depletion in the cytosolic ATP concentration related to neuron activation. NMDA 80 µM induces neuron activation by increasing pERK, Ca2+ influx, Δψm, and cytosolic ATP depletion. Conclusion: NMDA 80 µM is the optimum concentration to induce DRG neuron activation through the NMDA receptor pathway

Induction Motor Speed Control with Solar Cell Using MPPT Algorithm by Incremental Conductance Method

In the world, optimizing energy and finding new sources is important because of the increased consumption that occurred in all aspects of life. Nowadays, the world suffers of the reduction in the fossil fuel continuously. One solution to this problem is the sun and the photovoltaic (PV) cell. To get the benefits of PV, the DC/DC and DC/AC converters and inverters are combined in one set to get the better usage of these capabilities. Induction motor (IM) is the horsepower in the industry and will be considered the load in this work. The DC/DC Converter is used for control of IM speed in combination with maximum power point tracking (MPPT). Temperature and radiation change constantly over time, and the maximum energy should be tracked. This follow-up was performed using Incremental Conductance method (INC). INC is control buck-boost duty cycle converter. We get the best performance in INC technology and have less effect on the system. This algorithm uses INC of the MPPT to control half of horse power of IM. The sine pulse width modulation technique (SPWM) is used with three level inverters. Simulation on the Three-phase proves the efficiency of the suggested technique

Exploring <i>Ocimum basilicum</i>’s Secondary Metabolites: Inhibition and Molecular Docking against <i>Rhynchophorus ferrugineus</i> for Optimal Action

The objective of our work is to create a practical procedure to produce in vitro cell suspensions of O. basilicum and to ascertain the factors that encourage enhanced secondary metabolite production. We investigated the impact of these metabolites on Rhynchophorus ferrugineus’s adult and larval target enzymes. The explants were cultivated on Murashige and Skoog (MS) media with 0.1 to 1 mg/L plant growth regulators (PGRs) to create calluses. 2,4-Dichlorophenoxyacetic acid (2,4-D), kinetin, 1-naphthylacetic acid (NAA), and indole-3-butryic acid (IBA) at 0.5, 0.5, 0.1, and 1 mg/L, respectively, with 3% sucrose led to the highest biomass accumulation. In cell suspensions, the total phenolic content (TPC) and total flavonoid content (TFC) were 39.68 and 5.49 mg/g DW, respectively, with abiotic Verticillium dahliae as an activator. Rosmarinic acid, ursolic acid, nepetoidin A and B, salvigenin, and quercetin-3-O-rutinoside as flavonoids and phenolics were analyzed using UPLC-I TQD MS, with the highest concentrations reached after 40 days. The extract demonstrates insecticidal activity against the fourth-instar larvae of R. ferrugineus, with adults at 1197 µg/mL and 12.5 µg/larvae as LC50 and LD50 values. The extract inhibited acetylcholine esterase (AChE), acid phosphatases (ACPs), alkaline phosphatases (ALPs), and gamma-aminobutyric acid-transaminase (GABA-T) in larval tissue in vitro, with IC50 values of 124.2, 149.3, 157.8, and 204.8 µg/mL, and in vivo, with IC50 values of 157.2, 179.4, 185.3, and 241.6 µg/mL, after 24 h. Pure compounds identified the activity of the extract, showing the inhibition of AChE, ACPs, ALPs, and GABA-T with IC50 values ˂ 200 µg/mL (in vitro). The ABMET examination revealed good oral permeability, and docking tests showed that the compounds bind AChE, ACPs, ALPs, and GABA-T. These findings show that a green bioprocessing method such as an O. basilicum cell suspension is a quick and straightforward technique for producing phenolic compounds, and it may be used to develop sustainable bio-insecticides and new green procedures