International Journal of Molecular Sciences最新文献

In most mammals, postural soleus muscles are involved in the maintenance of the stability of the body in the gravitational field of Earth. It is well established that immediately after a laboratory rat is exposed to conditions of weightlessness (parabolic flight) or simulated microgravity (hindlimb suspension/unloading), a sharp decrease in soleus muscle electrical activity occurs. However, starting from the 3rd day of mechanical unloading, soleus muscle electrical activity begins to increase and reaches baseline levels approximately by the 14th day of hindlimb suspension. This phenomenon, observed in the course of rat hindlimb suspension, was named the "spontaneous electrical activity of postural muscle". The present review discusses spinal mechanisms underlying the development of such spontaneous activity of rat soleus muscle and the effect of this activity on intracellular signaling in rat soleus muscle during mechanical unloading.

Oxidative stress from environmental exposures is thought to play a role in neurodevelopmental disorders; therefore, understanding the underlying molecular regulatory network is essential for mitigating its impacts. In this study, we analysed the competitive endogenous RNA (ceRNA) network mediated by circRNAs, a novel class of regulatory molecules, in an SH-SY5Y cell model of oxidative stress, both prior to and during neural differentiation, using RNA sequencing and in silico analysis. We identified 146 differentially expressed circRNAs, including 93 upregulated and 53 downregulated circRNAs, many of which were significantly co-expressed with mRNAs that potentially interact with miRNAs. We constructed a circRNA-miRNA-mRNA network and identified 15 circRNAs serving as hubs within the regulatory axes, with target genes enriched in stress- and neuron-related pathways, such as signaling by VEGF, axon guidance, signaling by FGFR, and the RAF/MAP kinase cascade. These findings provide insights into the role of the circRNA-mediated ceRNA network in oxidative stress during neuronal differentiation, which may help explain the regulatory mechanisms underlying neurodevelopmental disorders associated with oxidative stress.

Type 2 diabetes mellitus (T2DM) is one of the most significant health issues worldwide, with associated healthcare costs estimated to surpass USD 1054 billion by 2045. The leading cause of death in T2DM patients is the development of cardiovascular disease (CVD). In the early stages of T2DM, patients develop cardiovascular autonomic dysfunction due to the withdrawal of cardiac parasympathetic activity. Diminished cardiac parasympathetic tone can lead to cardiac arrhythmia-related sudden cardiac death, which accounts for 50% of CVD-related deaths in T2DM patients. Regulation of cardiovascular parasympathetic activity is integrated by neural circuitry at multiple levels including afferent, central, and efferent components. Efferent control of cardiac parasympathetic autonomic tone is mediated through the activity of preganglionic parasympathetic neurons located in the cardiac extensions of the vagus nerve that signals to postganglionic parasympathetic neurons located in the intracardiac ganglia (ICG) on the heart. Postganglionic parasympathetic neurons exert local control on the heart, independent of higher brain centers, through the release of neurotransmitters, such as acetylcholine. Structural and functional alterations in cardiac parasympathetic postganglionic neurons contribute to the withdrawal of cardiac parasympathetic tone, resulting in arrhythmogenesis and sudden cardiac death. This review provides an overview of the remodeling of parasympathetic postganglionic neurons in the ICG, and potential mechanisms contributing to the withdrawal of cardiac parasympathetic tone, ventricular arrhythmogenesis, and sudden cardiac death in T2DM. Improving cardiac parasympathetic tone could be a therapeutic avenue to reduce malignant ventricular arrhythmia and sudden cardiac death, increasing both the lifespan and improving quality of life of T2DM patients.

The epidermis, the outer layer of the skin, relies on a delicate balance of cell growth and keratinocyte differentiation for its function and renewal. Recent research has shed light on exosomes' role in facilitating skin communication by transferring molecules like miRNAs, which regulate gene expression post-transcriptionally. Additionally, these factors lead to skin aging through oxidative stress caused by reactive oxygen species (ROS). In this research project, experiments were conducted to study the impact of Sun2000 solar simulator irradiation on exosomal miRNA profiles in HEKa cells. We hypothesized that acute oxidative stress induced by solar simulator irradiation would alter the expression profile of exosomal miRNAs in HEKa cells. The cells were exposed to different durations of irradiation to induce oxidative stress, and the levels of reactive ROS were measured using the CellROX Deep Red flow cytometry assay kit. Exosomes were isolated from both control and irradiated cells, characterized using DLS and SEM techniques, and their miRNAs were extracted and analyzed using qPCR. Solar simulator irradiation led to a time-dependent increase in intracellular ROS and a decrease in cell viability. Exosomal size increased in irradiated cells. Fifty-nine exosomal miRNAs were differentially expressed in irradiated HEKa cells, including hsa-miR-425-5p, hsa-miR-181b-5p, hsa-miR-196b-5p, hsa-miR-376c-3p, and hsa-miR-15a-5p. This study highlights the significant impact of solar radiation on exosomal miRNA expression in keratinocytes, suggesting their potential role in the cellular response to oxidative stress.

The goat breeding industry on the Tibetan Plateau faces strong selection pressure to enhance fertility. Consequently, there is an urgent need to develop goat lines with higher fertility and adaptability. The ovary, as a key organ determining reproductive performance, is regulated by a complex transcriptional network involving numerous protein-coding and non-coding genes. However, the molecular mechanisms of the key mRNA-miRNA-lncRNA regulatory network in goat ovaries remain largely unknown. This study focused on the histology and differential mRNA/miRNA/lncRNA between Chuanzhong black goat (CBG, high productivity, multiple births) and Tibetan goat (TG, strong adaptability, single birth) ovaries. Histomorphological analysis showed that the medulla proportion in CBG ovaries was significantly reduced compared to TG. RNA-Seq and small RNA-Seq analysis identified 1218 differentially expressed (DE) mRNAs, 100 DE miRNAs, and 326 DE lncRNAs, which were mainly enriched in ovarian steroidogenesis, oocyte meiosis, biosynthesis of amino acids and protein digestion, and absorption signaling pathways. Additionally, five key mRNA-miRNA-lncRNA interaction networks regulating goat reproductive performance were identified, including TCL1B-novel68_mature-ENSCHIT00000010023, AKAP6-novel475_mature-ENSCHIT00000003176, GLI2-novel68_mature-XR_001919123.1, ITGB5-novel65_star-TCONS_00013850, and VWA2-novel71_mature-XR_001919911.1. Further analyses showed that these networks mainly affected ovarian function and reproductive performance by regulating biological processes such as germ cell development and oocyte development, which also affected the plateau adaptive capacity of the ovary by participating in the individual immune and metabolic capacities. In conclusion, we identified numerous mRNA-miRNA-lncRNA interaction networks involved in regulating ovarian function and reproductive performance in goats. This discovery offers new insights into the molecular breeding of Tibetan Plateau goats and provides a theoretical foundation for developing new goat lines with high reproductive capacity and strong adaptability to the plateau environment.

The literature analysis conducted in this review discusses the latest achievements in the identification of cardiovascular damage induced by oxidative stress with secondary platelet mitochondrial dysfunction. Damage to the platelets of mitochondria as a result of their interactions with reactive oxygen species (ROS) and reactive nitrogen species (RNS) can lead to their numerous ischemic events associated with hypoxia or hyperoxia processes in the cell. Disturbances in redox reactions in the platelet mitochondrial membrane lead to the direct oxidation of cellular macromolecules, including nucleic acids (DNA base oxidation), membrane lipids (lipid peroxidation process) and cellular proteins (formation of reducing groups in repair proteins and amino acid peroxides). Oxidative changes in biomolecules inducing tissue damage leads to inflammation, initiating pathogenic processes associated with faster cell aging or their apoptosis. The consequence of damage to platelet mitochondria and their excessive activation is the induction of cardiovascular and neurodegenerative diseases (Parkinson's and Alzheimer's), as well as carbohydrate metabolism disorders (diabetes). The oxidation of mitochondrial DNA can lead to modifications in its bases, inducing the formation of exocyclic adducts of the ethano and propano type. As a consequence, it disrupts DNA repair processes and conduces to premature neoplastic transformation in critical genes such as the p53 suppressor gene, which leads to the development of various types of tumors. The topic of new innovative methods and techniques for the analysis of oxidative stress in platelet mitochondria based on methods such as a nicking assay, oxygen consumption assay, Total Thrombus formation Analysis System (T-Tas), and continuous-flow left ventricular assist devices (CF-LVADs) was also discussed. They were put together into one scientific and research platform. This will enable the facilitation of faster diagnostics and the identification of platelet mitochondrial damage by clinicians and scientists in order to implement adequate therapeutic procedures and minimize the risk of the induction of cardiovascular diseases, including ischemic events correlated with them. A quantitative analysis of the processes of thrombus formation in cardiovascular diseases will provide an opportunity to select specific anticoagulant and thrombolytic drugs under conditions of preserved hemostasis.

Bananas (Musa spp.) are among the most important fruit and staple food crops globally, holding a significant strategic position in food security in tropical and subtropical regions. However, the industry is grappling with a significant threat from Fusarium wilt, a disease incited by Fusarium oxysporum f. sp. cubense (Foc). In this study, we explored the potential of Piriformospora indica (Pi), a mycorrhizal fungus renowned for bolstering plant resilience and nutrient assimilation, to fortify bananas against this devastating disease. Through a meticulous comparative analysis of mRNA and miRNA expression in control, Foc-inoculated, Pi-colonized, and Pi-colonized followed by Foc-inoculated plants via transcriptome and sRNAome, we uncovered a significant enrichment of differentially expressed genes (DEGs) and DE miRNAs in pathways associated with plant growth and development, glutathione metabolism, and stress response. Our findings suggest that P. indica plays a pivotal role in bolstering banana resistance to Foc. We propose that P. indica modulates the expression of key genes, such as glutathione S-transferase (GST), and transcription factors (TFs), including TCP, through miRNAs, thus augmenting the plant's defensive capabilities. This study offers novel perspectives on harnessing P. indica for the management of banana wilt disease.

The effect of dark deprivation on the morphofunctional state and rhythmostasis of the liver under CCl₄ toxic exposure has been studied. The relevance of this study is due to the fact that the hepatotoxic effect of carbon tetrachloride on the liver is well studied, but there are very few data on the relationship between CCl₄ intoxication and circadian biorhythms, and most of the studies consider the susceptibility of the organism in general and of the liver in particular to the influence of CCl₄ in some separate periods of the rhythm, but not the influence of this chemical agent on the structure of the whole rhythm. In addition, earlier studies indicate that light disturbance causes certain changes in the morphofunctional state of the liver and the structure of the circadian rhythm of a number of parameters. As a result of this study, we found that the effect of CCl₄ in conditions of prolonged dark deprivation causes more significant structural and functional changes in hepatocytes, as well as leading to significant changes in the circadian rhythms of a number of parameters, which was not observed in the action of CCl₄ as a monofactor. We assume that the severity of structural and functional changes is due to the light-induced deficiency of melatonin, which has hepatoprotective properties. Thus, the mechanisms of CCl₄ action on CRs under conditions of light regime violations leave a large number of questions requiring further study, including the role of melatonin in these processes.

The central aim of this study was to investigate whether male Wistar rats chronically fed a high-fat diet (HFD) over 106 days present high levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and Na⁺ and Ca²⁺ transport alterations in the left ventricle, together with dyslipidemia and decreased glucose tolerance, and to investigate the influence of Ang-(3-4). The rats became moderately overweight with an expansion of visceral adiposity. Na⁺-transporting ATPases, sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles from plasma and left-ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). IL-6 and TNF-α increased (62% and 53%, respectively), but returned to normal levels with Angiotensin-(3-4) administration after 106 days. Significant lipidogram alterations accompanied a decrease in glucose tolerance. Angiotensin II receptors abundance did not change. (Na⁺ + K⁺)ATPase and ouabain-resistant Na⁺-ATPase were downregulated and upregulated, respectively, but returned to normal values upon Angiotensin-(3-4) administration. SERCA2a lost its ability to respond to excess ATP. Echocardiography showed no changes in FS or EF. We conclude that being overweight causes an increase in Ang-(3-4)-sensitive IL-6 and TNF-α levels, and ion transport alterations in the left ventricle that could evolve into future heart dysfunction.

The present review investigates the relationship between polyunsaturated fatty acids (PUFAs) and mental health disorders, such as dementia, psychosis, schizophrenia, Alzheimer's disease, anorexia nervosa, and impairment problems in animals and human models. Data were collected from a variety of studies: randomized intervention trials, observational and interventional studies, case reports, and epidemiological studies. The evidence suggests that PUFAs are beneficial for mental health, brain function, and behavior. ALA, EPA, and DHA have very significant neuroprotective properties, particularly in inducing changes to the synaptic membrane and modulating brain cell signaling. In the case of neurodegenerative disorders, PUFAs incorporated into cellular membranes have been shown to protect against cell atrophy and death. The formal analyses of the included studies pointed to a decrease in ALA, EPA, and DHA levels in various populations (e.g., children, adolescents, adults, and seniors) presenting with different types of mental disorders. These results indicate that PUFA supplementation may be considered as an innovative therapeutic strategy to reduce the risk of neuronal degeneration.