Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet

Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune cells, its activation regulating inflammatory cytokines and chemotactic factor secretion. Recently, a Lox-1 truncated protein isoform lacking the ox-LDL binding domain named LOXIN has been described. We have previously shown that LOXIN overexpression blocked Lox-1-mediated ox-LDL internalization in human endothelial progenitor cells in vitro. However, the functional role of LOXIN in targeting inflammation or tissue injury in vivo remains unknown. In this study, we investigate whether LOXIN modulated the expression of Lox-1 and reduced the inflammatory response in a high-fat-diet mice model. Results indicate that human LOXIN blocks Lox-1 mediated uptake of ox-LDL in H4-II-E-C3 cells. Furthermore, in vivo experiments showed that overexpression of LOXIN reduced both fatty streak lesions in the aorta and inflammation and fibrosis in the liver. These findings were associated with the down-regulation of Lox-1 in endothelial cells. Then, LOXIN prevents hepatic and aortic tissue damage in vivo associated with reduced Lox-1 expression in endothelial cells. We encourage future research to understand better the underlying molecular mechanisms and potential therapeutic use of LOXIN.     

Experimental Evidence for Seed Metabolic Allometry in Barrel Medic (Medicago truncatula Gaertn.)

Seed size is often considered to be an important trait for seed quality, i.e., vigour and germination performance. It is believed that seed size reflects the quantity of reserve material and thus the C and N sources available for post-germinative processes. However, mechanisms linking seed size and quality are poorly documented. In particular, specific metabolic changes when seed size varies are not well-known. To gain insight into this aspect, we examined seed size and composition across different accessions of barrel medic (Medicago truncatula Gaertn.) from the genetic core collection. We conducted multi-elemental analyses and isotope measurements, as well as exact mass GC–MS metabolomics. There was a systematic increase in N content (+0.17% N mg⁻¹) and a decrease in H content (–0.14% H mg⁻¹) with seed size, reflecting lower lipid and higher S-poor protein quantity. There was also a decrease in ²H natural abundance (δ²H), due to the lower prevalence of ²H-enriched lipid hydrogen atoms that underwent isotopic exchange with water during seed development. Metabolomics showed that seed size correlates with free amino acid and hexoses content, and anticorrelates with amino acid degradation products, disaccharides, malic acid and free fatty acids. All accessions followed the same trend, with insignificant differences in metabolic properties between them. Our results show that there is no general, proportional increase in metabolite pools with seed size. Seed size appears to be determined by metabolic balance (between sugar and amino acid degradation vs. utilisation for storage), which is in turn likely determined by phloem source metabolite delivery during seed development.     

Subharmonic Resonance Behavior for the Classical Hydrogen Atomic System

Previously unexplored resonance conditions are shown to exist for the classical hydrogen atomic system, where the electron is treated as a classical charged point particle following the nonrelativistic Lorentz-Dirac equation of motion about a stationary nucleus of opposite charge. For circularly polarized (CP) light directed normal to the orbit, very pronounced subharmonic resonance behavior is shown to occur with a variety of interesting properties. In particular, only if the amplitude of the CP light exceeds a critical value, will the resonance continue without radius and energy decay. A perturbation analysis is carried out to illustrate the main features of the behavior. The present phenomena adds to a growing list of other nonlinear dynamical behaviors of this simple system, that may well be important for more deeply understanding classical and quantum connections.     

Effective Natural Killer Cell Degranulation Is an Essential Key in COVID-19 Evolution

NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.     

TRPA1 Role in Inflammatory Disorders: What Is Known So Far?

The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, is primarily localized in a subpopulation of primary sensory neurons of the trigeminal, vagal, and dorsal root ganglia, where its activation mediates neurogenic inflammatory responses. TRPA1 expression in resident tissue cells, inflammatory, and immune cells, through the indirect modulation of a large series of intracellular pathways, orchestrates a range of cellular processes, such as cytokine production, cell differentiation, and cytotoxicity. Therefore, the TRPA1 pathway has been proposed as a protective mechanism to detect and respond to harmful agents in various pathological conditions, including several inflammatory diseases. Specific attention has been paid to TRPA1 contribution to the transition of inflammation and immune responses from an early defensive response to a chronic pathological condition. In this view, TRPA1 antagonists may be regarded as beneficial tools for the treatment of inflammatory conditions.     

Unsaturated Copolyesters from Macrolactone/Norbornene: Toward Reaction Kinetics of Metathesis Copolymerization Using Ruthenium Carbene Catalysts

Unsaturated copolyesters are of great interest in polymer science due to their broad potential applications and sustainability. Copolyesters were synthesized from the ring-opening metathesis copolymerization of ω-6-hexadecenlactone (HDL) and norbornene (NB) using ruthenium-alkylidene [Ru(Cl₂)(=CHPh)(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)(PCy₃)] (Ru1), [Ru(Cl)₂(=CHPh)(PCy₃)₂] (Ru2), and ruthenium-vinylidene [RuCl₂(=C=CH(p-C₆H₄CF₃))(PCy₃)₂] (Ru3) catalysts, respectively, yielding HDL-NB copolymers with different ratios of the monomer HDL in the feed. The activity of N-heterocyclic-carbene (NHC) (Ru1) and phosphine (Ru2 and Ru3) ligands containing ruthenium-carbene catalysts were evaluated in the synthesis of copolymer HDL-NB. The catalysts Ru1 with an NHC ligand showed superior activity and stability over catalysts Ru2 and Ru3 bearing PCy₃ ligands. The incorporation of the monomers in the copolymers determined by ¹H-NMR spectroscopy was similar to that of the HDL-NB values in the feed. Experiments, at distinct monomer molar ratios, were carried out using the catalysts Ru1–Ru3 to determine the copolymerization reactivity constants by applying the Mayo–Lewis and Fineman–Ross methods. The copolymer distribution under equilibrium conditions was studied by the ¹³C NMR spectra, indicating that the copolymer HDL-NB is a gradient copolymer. The main factor determining the decrease in melting temperature is the inclusion of norbornene units, indicating that the PNB units permeate trough the HDL chains. The copolymers with different molar ratios [HDL]/[NB] have good thermal stability up to 411 °C in comparison with the homopolymer PHDL (384 °C). Further, the stress–strain measurements in tension for these copolymers depicted the appreciable increment in stress values as the NB content increases.     

Leptin Signaling in Obesity and Colorectal Cancer

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin’s relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.