Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice

The mammalian retina contains approximately 30 neuropeptides that are synthetized by different neuronal cell populations, glia, and the pigmented epithelium. The presence of these neuropeptides leaves a mark on normal retinal molecular processes and physiology, and they are also crucial in fighting various pathologies (e.g., diabetic retinopathy, ischemia, age-related pathologies, glaucoma) because of their protective abilities. Retinal pathologies of different origin (metabolic, genetic) are extensively investigated by genetically manipulated in vivo mouse models that help us gain a better understanding of the molecular background of these pathomechanisms. These models offer opportunities to manipulate gene expression in different cell types to help reveal their roles in the preservation of retinal health or identify malfunction during diseases. In order to assess the current status of transgenic technologies available, we have conducted a literature survey focused on retinal disorders of metabolic origin, zooming in on the role of retinal neuropeptides in diabetic retinopathy and ischemia. First, we identified those neuropeptides that are most relevant to retinal pathologies in humans and the two clinically most relevant models, mice and rats. Then we continued our analysis with metabolic disorders, examining neuropeptide-related pathways leading to systemic or cellular damage and rescue. Last but not least, we reviewed the available literature on genetically modified mouse strains to understand how the manipulation of a single element of any given pathway (e.g., signal molecules, receptors, intracellular signaling pathways) could lead either to the worsening of disease conditions or, more frequently, to substantial improvements in retinal health. Most attention was given to studies which reported successful intervention against specific disorders. For these experiments, a detailed evaluation will be given and the possible role of converging intracellular pathways will be discussed. Using these converging intracellular pathways, curative effects of peptides could potentially be utilized in fighting metabolic retinal disorders.

Disposable Stainless-Steel Wire-Based Electrochemical Microsensor for In Vivo Continuous Monitoring of Hydrogen Peroxide in Vein of Tomato Leaf

As one of the pivotal signal molecules, hydrogen peroxide (H2O2) has been demonstrated to play important roles in many physiological processes of plants. Continuous monitoring of H2O2 in vivo could help understand its regulation mechanism more clearly. In this study, a disposable electrochemical microsensor for H2O2 was developed. This microsensor consists of three parts: low-cost stainless-steel wire with a diameter of 0.1 mm modified by gold nanoparticles (disposable working electrode), an untreated platinum wire with a diameter of 0.1 mm (counter electrode), and an Ag/AgCl wire with a diameter of 0.1 mm (reference electrode), respectively. The microsensor could detect H2O2 in levels from 10 to 1000 µM and exhibited excellent selectivity. On this basis, the dynamic change in H2O2 in the vein of tomato leaf under high salinity was continuously monitored in vivo. The results showed that the production of H2O2 could be induced by high salinity within two hours. This study suggests that the disposable electrochemical microsensor not only suits continuously detecting H2O2 in microscopic plant tissue in vivo but also reduces the damage to plants. Overall, our strategy will help to pave the foundation for further investigation of the generation, transportation, and elimination mechanism of H2O2 in plants.

Positive Effect of Lactobacillus acidophilus EG004 on Cognitive Ability of Healthy Mice by Fecal Microbiome Analysis Using Full-Length 16S-23S rRNA Metagenome Sequencing

Recently, the concept of the “gut-brain axis” has risen and suggested that microbes in the GI tract affect the brain by modulating signal molecules. Although many pieces of research were reported in a short period, a signaling mechanism and the effects of a specific bacterial strain are still unclear.

Hydrogen: A Novel Treatment Strategy in Kidney Disease

<b><i>Background:</i></b> Hydrogen is a chemical substance that has yet to be widely used in medicine. However, recent evidence indicates that hydrogen has multi-faceted pharmacological effects such as antioxidant, anti-inflammatory, and antiapoptotic properties. An increased number of studies are being conducted on the application of hydrogen in various diseases, especially those affecting the renal system. <b><i>Summary:</i></b> Hydrogen can be inhaled, as a gas or liquid, and can be administered orally, intravenously, or locally. Hydrogen can rapidly enter suborganelles such as mitochondria and nucleus by simple diffusion, producing reactive oxygen species (ROS) and triggering DNA damage. Hydrogen can selectively scavenge hydroxyl radical (•OH) and peroxynitrite (ONOO⁻), but not other reactive oxygen radicals with physiological functions, such as peroxyanion (O₂⁻) and hydrogen peroxide (H₂O₂). Although the regulatory effect of hydrogen on the signal transduction pathway has been confirmed, the specific mechanism of its influence on signal molecules remains unknown. Although many studies have investigated the therapeutic and preventive effects of H₂ in cellular and animal experiments, clinical trials are few and still far behind. As a result, more clinical trials are required to investigate the role of hydrogen in kidney disease, as well as the effect of its dose, timing, and form on the overall efficacy. Large-scale randomized controlled clinical trials will be required before hydrogen can be used to treat renal illnesses. <b><i>Key Messages:</i></b> This article reviews the mechanisms of hydrogen in the treatment of renal disease and explores the possibilities of its use in clinical practice.

Agr Quorum Sensing influences the Wood-Ljungdahl pathway in Clostridium autoethanogenum

Acetogenic bacteria are capable of fermenting CO2 and carbon monoxide containing waste-gases into a range of platform chemicals and fuels. Despite major advances in genetic engineering and improving these biocatalysts, several important physiological functions remain elusive. Among these is quorum sensing, a bacterial communication mechanism known to coordinate gene expression in response to cell population density. Two putative agr systems have been identified in the genome of Clostridium autoethanogenum suggesting bacterial communication via autoinducing signal molecules. Signal molecule-encoding agrD1 and agrD2 genes were targeted for in-frame deletion. During heterotrophic growth on fructose as a carbon and energy source, single deletions of either gene did not produce an observable phenotype. However, when both genes were simultaneously inactivated, final product concentrations in the double mutant shifted to a 1.5:1 ratio of ethanol:acetate, compared to a 0.2:1 ratio observed in the wild type control, making ethanol the dominant fermentation product. Moreover, CO2 re-assimilation was also notably reduced in both hetero- and autotrophic growth conditions. These findings were supported through comparative proteomics, which showed lower expression of carbon monoxide dehydrogenase, formate dehydrogenase A and hydrogenases in the ∆agrD1∆agrD2 double mutant, but higher levels of putative alcohol and aldehyde dehydrogenases and bacterial micro-compartment proteins. These findings suggest that Agr quorum sensing, and by inference, cell density play a role in carbon resource management and use of the Wood-Ljungdahl pathway as an electron sink.

Plant Flavonoids in Mediterranean Species: A Focus on Flavonols as Protective Metabolites under Climate Stress

Flavonoids are specialized metabolites largely widespread in plants where they play numerous roles including defense and signaling under stress conditions. These compounds encompass several chemical subgroups such as flavonols which are one the most represented classes. The most studied flavonols are kaempferol, quercetin and myricetin to which research attributes antioxidative properties and a potential role in UV-defense through UV-screening mechanisms making them critical for plant adaptation to climate change. Despite the great interest in flavonol functions in the last decades, some functional aspects remain under debate. This review summarizes the importance of flavonoids in plant defense against climate stressors and as signal molecules with a focus on flavonols in Mediterranean plant species. The review emphasizes the relationship between flavonol location (at the organ, tissue and cellular scales) and their function as defense metabolites against climate-related stresses. It also provides evidence that biosynthesis of flavonols, or flavonoids as a whole, could be a crucial process allowing plants to adapt to climate change, especially in the Mediterranean area which is considered as one of the most sensitive regions to climate change over the globe.

Meta-analysis of whole-genome gene expression datasets assessing the effects of IDH1 and IDH2 mutations in isogenic disease models

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are oncogenic drivers to a variable extent in several tumors, including gliomas, acute myeloid leukemia (AML), cholangiocarcinoma, melanoma, and thyroid carcinoma. The pathobiological effects of these mutations vary considerably, impeding the identification of common expression profiles. We performed an expression meta-analysis between IDH-mutant (IDHmut) and IDH-wild-type (IDHwt) conditions in six human and mouse isogenic disease models. The datasets included colon cancer cells, glioma cells, heart tissue, hepatoblasts, and neural stem cells. Among differentially expressed genes (DEGs), serine protease 23 (PRSS23) was upregulated in four datasets, i.e., in human colon carcinoma cells, mouse heart tissue, mouse neural stem cells, and human glioma cells. Carbonic anhydrase 2 (CA2) and prolyl 3-hydroxylase 2 (P3H2) were upregulated in three datasets, and SOX2 overlapping transcript (SOX2-OT) was downregulated in three datasets. The most significantly overrepresented protein class was termed intercellular signal molecules. An additional DEG set contained genes that were both up- and downregulated in different datasets and included oxidases and extracellular matrix structural proteins as the most significantly overrepresented protein classes. In conclusion, this meta-analysis provides a comprehensive overview of the expression effects of IDH mutations shared between different isogenic disease models. The generated dataset includes biomarkers, e.g., PRSS23 that may gain relevance for further research or clinical applications in IDHmut tumors.

Nanoparticles in Agriculture: Characterization, Uptake and Role in Mitigating Heat Stress

Abiotic stresses like heat, drought, and salinity are among the major threats to sustainable crop production. These stresses induce numerous adverse effects in plants by impairing biochemical, physiological and molecular processes, eventually affecting plant growth, development and productivity. The rising temperature is one of the major causes of heat stress in agriculture. The variation in temperature during crop development has led to devastating agricultural losses in terms of yield. To adapt and mitigate these effects, germplasm scientists and agronomists aim to develop heat-tolerant varieties or cultivars. These efforts generally include the identification of alleles responsible for heat tolerance and their introgression into breeding populations through conventional or biotechnological methods. However, heat tolerance is a very complex physio-biochemical response of plants governed by a number of genes positioned at different loci. The accumulation of various additive gene effects into a single genotype is an extremely tedious and time-consuming process in both plant breeding and biotechnology. Recent advancements in agricultural nanotechnology have raised expectations for sustainable productivity without altering the genetic make-up of plants. In this milieu, the application of biologically active nanoparticles (NPs) could be a novel approach to enhance heat tolerance in crops. Recently, the NPs from silver, silicon, titanium and selenium have been proven valuable for plants to combat heat stress by altering their physiological and biochemical responses. Due to nano-scale size and the high surface area along with their slow and steady release, the NPs exert positive effects in plants through their growth-promoting and antioxidant capabilities. In this review, various technologies used for NPs characterization and their applications in agriculture have been discussed. The review further elaborates the uptake mechanism of NPs and their translocation in different plant parts along with the factors affecting them. This article also describes the role of metal or metal oxide NPs, as well as nano, encapsulated plant growth regulators and signal molecules in heat stress tolerance. The review will provide an insight to the scientists working in the area of agricultural sciences to explore new NPs to encounter different types of biotic and abiotic stresses.

Exosomes Regulate NLRP3 Inflammasome in Diseases

Emerging evidence has suggested the unique and critical role of exosomes as signal molecules vector in various diseases. Numerous researchers have been trying to identify how these exosomes function in immune progression, as this could promote their use as biomarkers for the disease process and potential promising diagnostic tools. NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3), a tripartite protein, contains three functional domains a central nucleotide-binding and oligomerization domain (NACHT), an N-terminal pyrin domain (PYD), and a leucine-rich repeat domain (LRR). Of note, existing studies have identified exosome as a novel mediator of the NLRP3 inflammasome, which is critical in diseases progression. However, the actual mechanisms and clinical treatment related to exosomes and NLRP3 are still not fully understood. Herein, we presented an up-to-date review of exosomes and NLRP3 in diseases, outlining what is known about the role of exosomes in the activation of NLRP3 inflammasome and also highlighting areas of this topic that warrant further study.