Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal

4-hydroxy-2,3-trans-nonenal (C9H16O2), also known as 4-hydroxy-2E-nonenal (C9H16O2; HNE) is an α,β-unsaturated hydroxyalkenal. HNE is a major aldehyde, formed in the peroxidation process of ω-6 polyunsaturated fatty acids (ω-6 PUFAs), such as linoleic and arachidonic acid. HNE is not only harmful but also beneficial. In the 1980s, the HNE was regarded as a “toxic product of lipid peroxidation” and the “second toxic messenger of free radicals”. However, already at the beginning of the 21st century, HNE was perceived as a reliable marker of oxidative stress, growth modulating factor and signaling molecule. Many literature data also indicate that an elevated level of HNE in blood plasma and cells of the animal and human body is observed in the course of many diseases, including cancer. On the other hand, it is currently proven that cancer cells divert to apoptosis if they are exposed to supraphysiological levels of HNE in the cancer microenvironment. In this review, we briefly summarize the current knowledge about the biological properties of HNE.

Benzyl Farnesyl Amine Mimetics are Potent Inhibitors of the Sterol Biosynthesis Pathway in Leishmania Amazonensis Leading to Oxidative Stress, Growth Arrest, and Ultrastructural Alterations

Leishmaniasis is a neglected disease caused by protozoan parasites of the Leishmania genus spread around the world. Benzyl farnesyl amine mimetics are known class of compounds selectively designed to inhibit the squalene synthase (SQS) enzyme that catalyzes the first committed reaction on the sterol biosynthesis pathway. Herein, we studied seven new benzyl farnesyl amine mimetics (SBC 37 - 43) against Leishmania amazonensis. After the first initial screening of cell viability, two inhibitors (SBC 39 and SBC 40) were selected for further studies. Against intracellular amastigotes, SBC 39 and SBC 40 presented selectivity indexes of 117.7 and 180, respectively, indicating that they are highly selective. Analyses of free sterol showed that SBC 39 and SBC 40 inhibit two enzymes, sterol Δ8 → Δ7 isomerase and SQS, resulting in depletion of endogenous 24-methyl sterols. Physiological analysis and electron microscopy revealed three main alterations: 1) in the mitochondrion ultrastructure and function; 2) the presence of lipid bodies and autophagosomes; and 3) the appearance of projections in the plasma membrane and extracellular vesicles inside the flagellar pocket. In conclusion, our results support the notion that benzyl farnesyl amine mimics have a potent effect against Leishmania amazonensis and should be an interesting novel pharmaceutical lead for the development of new chemotherapeutic alternatives to treat leishmaniasis.

The Emerging Role of FUNDC1-Mediated Mitophagy in Cardiovascular Diseases

Mitochondria are highly dynamic organelles and play essential role in ATP synthase, ROS production, innate immunity, and apoptosis. Mitochondria quality control is critical for maintaining the cellular function in response to cellular stress, growth, and differentiation Signals. Damaged or unwanted mitochondria are selectively removed by mitophagy, which is a crucial determinant of cell viability. Mitochondria-associated Endoplasmic Reticulum Membranes (MAMs) are the cellular structures that connect the ER and mitochondria and are involved in calcium signaling, lipid transfer, mitochondrial dynamic, and mitophagy. Abnormal mitochondrial quality induced by mitophagy impairment and MAMs dysfunction is associated with many diseases, including cardiovascular diseases (CVDs), metabolic syndrome, and neurodegenerative diseases. As a mitophagy receptor, FUNDC1 plays pivotal role in mitochondrial quality control through regulation of mitophagy and MAMs and is closely related to the occurrence of several types of CVDs. This review covers the regulation mechanism of FUNDC1-mediated mitophagy and MAMs formation, with a particular focus on its role in CVDs.

Silicon-Mediated Regulation of Sodium Distribution in Barley Plants

Salinity is one of the largest problems in the world today. Silicon (Si)-mediated increase in plant tolerance to saline environment has been well documented, while the underlying mechanisms remain unclear. Monosilicic acid, polysilicic acid, and sodium (Na) were analyzed in the apoplast and symplast of roots, stems and leaves of salt-stressed barley plants in dynamics. Sodium moved predominantly via apoplastic pathway. The dynamics of Na in apoplast represented a parabolic curve. Soluble Si in nutrient solution increased the total Na in the roots but restricted the Na root-to-shoot transport via apoplastic pathway and reduced Na accumulation in stems and leaves. Plant exposure to high concentration of Na resulted in increased polysilicic acids in the root symplast and stem apoplast and symplast. These increases are attributable to Si redistribution within plant with its accumulation in stressed tissue. Probably, Si moves in the form of polysilicic acid. Under optimum or low stress growth conditions, Si mainly accumulated in the roots and leaves. Under higher stress, this Si can be redistributed to a mostly stress-affected place.

Thixotropic Behavior in Defining Particle Packing Density of Highly Filled AP/HTPB-Based Propellant

An alarming, asymmetric flame in rocket combustion originates from a composite solid propellant (CSP) containing defects. The defects are the result of a composition that exceeds the maximum particle packing density. Based on the structure analysis of CSP, the addition of plasticizer causes the correlation between the viscosity of CSP slurry and particle packing density to become uncertain. This work aims to investigate the influence of thixotropic behavior on the maximum particle packing density of CSP. A CSP with different thixotropic behavior was successfully produced using aluminum/plasticizer dioctyl adipate (DOA) of 12–24. During the curing process, viscosity and stress–growth were investigated. The structure of the CSP was defined using X-ray radiography. It is remarkably observed that the peak of thixotropy occurred at the 15th minute of the curing process. The particle packing density of CSP can be decisive for the relative viscosity at the peak time of thixotropic behavior. The CSP with the highest relative viscosity at the peak time was revealed to have voids in the upper part of the CSP. Thus, this parameter was proven to change the preceding parameter, viscosity that was measured at the end of mixing. Based on the stress–growth analysis, it is conceivable that the mechanism involves the time-dependent diffusion of DOA in weakening aluminum agglomerates.

miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact proteotoxicity and muscle function during aging

Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also plastic, and remodeled in response to stress, growth, neural and metabolic inputs. The conserved muscle-enriched microRNA, miR-1, regulates distinct aspects of muscle development, but whether it plays a role during aging is unknown. Here we investigated Caenorhabditis elegans miR-1 in muscle function in response to proteostatic stress. mir-1 deletion improved mid-life muscle motility, pharyngeal pumping, and organismal longevity upon polyQ35 proteotoxic challenge. We identified multiple vacuolar ATPase subunits as subject to miR-1 control, and the regulatory subunit vha-13/ATP6V1A as a direct target downregulated via its 3′UTR to mediate miR-1 physiology. miR-1 further regulates nuclear localization of lysosomal biogenesis factor HLH-30/TFEB and lysosomal acidification. Our studies reveal that miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact muscle function and health during aging.

Effects Of Seed Priming On Root- Shoot Behaviour And Stress Tolerance Of Pea (Pisum Sativum L.)

A pot culture experiment was carried out under controlled conditions for the detailed study of morphophysiological and advanced stress response adaptive mechanisms along with yield performance of pea varieties under the influence of seed priming substances. The performances of selected seed priming substances in different pea varieties were tested with water stress. Growth and physiological parameters documented at the stress period. From the experiment, it can be inferred that seed priming substances like KH2PO4 (1.5 and 3%), H2O2 (10 mM) and PEG (5%) were significantly outperformed in inducing higher growth with positive physiological changes. Bangladesh J. Bot. 50(2): 199-208, 2021 (June)