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Diabetes mellitus (DM) is one of the most prevalent metabolic disorders that poses a global threat to human health. It can lead to complications in multiple organs and tissues, owing to its wide-ranging impact on the human body. Diabetic cardiomyopathy (DCM) is a specific cardiac manifestation of DM, which is characterized by heart failure in the absence of coronary heart disease, hypertension and valvular heart disease. Given that oxidative stress is a key factor in the pathogenesis of DCM, intervening to mitigate oxidative stress may serve as a therapeutic strategy for managing DCM. Naringenin is a natural product with anti-oxidative stress properties that can suppress oxidative damage by regulating various oxidative stress signaling pathways. In this review, we address the relationship between oxidative stress and its primary signaling pathways implicated in DCM, and explores the therapeutic potential of naringenin in DCM. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with an increased risk of death, but its underlying mechanisms are not fully understood. Circular RNAs (circRNAs) have recently been implicated in various biological processes. The aim of this study was to investigate the key circRNAs related to RA. A microarray assay was used to identify the differentially expressed circRNAs (DEcircRNAs) in peripheral blood mononuclear cells (PBMCs) from patients with RA compared to patients with osteoarthritis (OA) and healthy controls. Then, quantitative real-time PCR was applied to verify the DEcircRNAs, and correlations between the levels of DEcircRNAs and laboratory indices were analysed. We also performed extensive bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway and potential circRNA–miRNA–mRNA network analyses to predict the function of these DEcircRNAs. A total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively. Nine out of the DEcircRNAs in RA were validated by real-time PCR. There were correlations between the levels of DEcircRNAs and some of the laboratory indices. GO analyses revealed that these DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, cell cycle, posttranslational protein modification and collagen formation. Functional annotation of host genes of these DEcircRNAs was implicated in several significantly enriched pathways, including metabolic pathways, ECM–receptor interaction, the PI3K–Akt signalling pathway, the AMPK signalling pathway, leukocyte transendothelial migration, platelet activation and the cAMP signalling pathway, which might be responsible for the pathophysiology of RA. The findings of this study may help to elucidate the role of circRNAs in the specific mechanism underlying RA. Microarray assays showed that a total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively. Nine out of the DEcircRNAs in RA were validated by real-time PCR, and the levels of the DEcircRNAs were related to some of the laboratory indices. GO analyses revealed that the DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, etc. Functional annotation of host genes of the DEcircRNAs in RA was implicated in several significantly enriched pathways, including metabolic pathways, ECM–receptor interaction, the PI3K–Akt signalling pathway, etc. [ABSTRACT FROM AUTHOR]

Our recent multi-omics studies have revealed rich sources of novel bioactive proteins and polypeptides from marine organisms including cnidarians. In the present study, we initially conducted a transcriptomic analysis to review the composition profile of polypeptides from Zoanthus sociatus. Then, a newly discovered NPY-like polypeptide-ZoaNPY was selected for further in silico structural, binding and virtually pharmacological studies. To evaluate the pro-angiogenic effects of ZoaNPY, we employed an in vitro HUVECs model and an in vivo zebrafish model. Our results indicate that ZoaNPY, at 1–100 pmol, enhances cell survival, migration and tube formation in the endothelial cells. Besides, treatment with ZoaNPY could restore a chemically-induced vascular insufficiency in zebrafish embryos. Western blot results demonstrated the application of ZoaNPY could increase the phosphorylation of proteins related to angiogenesis signaling including PKC, PLC, FAK, Src, Akt, mTOR, MEK, and ERK1/2. Furthermore, through molecular docking and surface plasmon resonance (SPR) verification, ZoaNPY was shown to directly and physically interact with NPY Y2 receptor. In view of this, all evidence showed that the pro-angiogenic effects of ZoaNPY involve the activation of NPY Y2 receptor, thereby activating the Akt/mTOR, PLC/PKC, ERK/MEK and Src- FAK-dependent signaling pathways. Furthermore, in an excision wound model, the treatment with ZoaNPY was shown to accelerate the wound healing process in mice. Our findings provide new insights into the discovery and development of novel pro-angiogenic drugs derived from NPY-like polypeptides in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective. Forsythia suspensa leaf (FSL) has been used as a health tea in China for centuries. Previous experiments have proved that FSL extract has a good effect on the antirespiratory syncytial virus (RSV) in vitro, but its exact mechanism is not clear. Therefore, this study aims to determine the active components and targets of FSL and further explore its anti-RSV mechanism. Methods. UPLC-Q-Exactive-MS was used to analyze the main chemical components of FSL. The compound disease target network, PPI, GO, and KEGG were used to obtain key targets and potential ways. Then, the molecular docking was verified by Schrödinger Maestro software. Next, the cell model of RSV infection was established, and the inhibitory effect of each drug on RSV was detected. Finally, western blotting was used to detect the effect of the active components of FSL on the expression of PI3K/AKT signaling pathway-related protein. Results. UPLC-Q-Exactive-MS analysis showed that there were 67 main chemical constituents in FSL, while network pharmacological analysis showed that there were 169 anti-RSV targets of the active components in FSL, involving 177 signal pathways, among which PI3K/AKT signal pathway played an important role in the anti-RSV process of FSL. The results of molecular docking showed that cryptochlorogenic acid, phillyrin, phillygenin, rutin, and rosmarinic acid had higher binding activities to TP53, STAT3, MAPK1, AKT1, and MAPK3, respectively. In vitro experiments showed that phillyrin and rosmarinic acid could effectively improve the survival rate of RSV-infected cells, increase the expression level of PI3K, and decrease the expression level of AKT. Conclusion. The active ingredients of FSL, phillyrin, and rosmarinic acid can play an anti-RSV role by inhibiting PI3K/AKT signaling pathway. This study provides reliable theoretical and experimental support for the anti-RSV treatment of FSL. [ABSTRACT FROM AUTHOR]

As one of the cash crops, cotton is facing the threat of abiotic stress during its growth and development. It has been reported that melatonin is involved in plant defense against salt stress, but whether melatonin can improve cotton salt tolerance and its molecular mechanism remain unclear. We investigated the role of melatonin in cotton salt tolerance by silencing melatonin synthesis gene and exogenous melatonin application in upland cotton. In this study, applicating of melatonin can improve salt tolerance of cotton seedlings. The content of endogenous melatonin was different in cotton varieties with different salt tolerance. The inhibition of melatonin biosynthesis related genes and endogenous melatonin content in cotton resulted in the decrease of antioxidant enzyme activity, Ca2+ content and salt tolerance of cotton. To explore the protective mechanism of exogenous melatonin against salt stress by RNA-seq analysis. Melatonin played an important role in the resistance of cotton to salt stress, improved the salt tolerance of cotton by regulating antioxidant enzymes, transcription factors, plant hormones, signal molecules and Ca2+ signal transduction. This study proposed a regulatory network for melatonin to regulate cotton's response to salt stress, which provided a theoretical basis for improving cotton's salt tolerance. [ABSTRACT FROM AUTHOR]

Aim of the Study. This study is aimed at exploring the effects and pharmacological mechanisms of the extracts from the Heritiera littoralis fruit (EFH) on dextran sulfate sodium- (DSS-) induced ulcerative colitis (UC) in mice. Materials and Methods. The chemical compositions of EFH were identified using LC-ESI-MS. The mice with 3% DSS-induced UC were administered EFH (200, 400, and 800 mg/kg), sulfasalazine (SASP, 200 mg/kg), and azathioprine (AZA, 13 mg/kg) for 10 days via daily gavage. The colonic inflammation was evaluated by the disease activity index (DAI), colonic length, histological scores, and levels of inflammatory mediators. The gut microbiota was characterized by 16S rRNA gene sequencing and analysis. Results. LC-ESI-MS analysis showed that EFH was rich in alkaloids and flavones. The results indicated that EFH significantly improved the DAI score, relieved colon shortening, and repaired pathological colonic variations in colitis. In addition, proteins in the NF-κB pathway were significantly inhibited by EFH. Furthermore, EFH recovered the diversity and balance of the gut microbiota. Conclusions. EFH has protective effects against DSS-induced colitis by keeping the balance of the gut microbiota and suppressing the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation plays a significant role in the occurrence and development of non‐small cell lung cancer (NSCLC). Hydroxysafflor yellow A (HSYA), a chemical compound of the yellow color pigments extracted from the safflower, has been widely used in clinical treatment with positive antioxidation, anti‐inflammation, and antitumor effects. However, the role and underlying mechanisms of HYSA on development and progress in inflammation‐mediated NSCLC are unknown. Methods: Cell counting kit‐8, colony formation, EdU, cell apoptosis, wound healing, Transwell migration and invasion, and enzyme‐linked immunosorbent assays; flow cytometry; and Western blotting were conducted using human NSCLC cell lines A549 and H1299. Results: Lipopolysaccharide (LPS) significantly promoted the proliferation and enhanced colony formation of A549 and H1299 cells, while HYSA notably reversed the effects of LPS. HYSA induced apoptosis of LPS‐mediated A549 and H1299 cells in a dose dependent manner; and remarkably suppressed migration, invasion, and epithelial–mesenchymal transition (EMT), significantly regulated production of LPS‐induced inflammation cytokines, and downregulated protein expression of PI3K/Akt/mTOR and ERK/MAPK signaling pathways in LPS‐induced A549 and H1299 cells. Furthermore, PI3K (LY294002) and ERK (SCH772984) inhibitors remarkably inhibited proliferation, migration, invasion, and EMT, and induced apoptosis in LPS‐mediated A549 and H1299 cells. These effects were even more obvious in the presence of HYSA and LY294002 or SCH772984 compared to those of either agent alone. Conclusion: HYSA suppressed LPS‐mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation‐mediated NSCLC. [ABSTRACT FROM AUTHOR]

Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone formation and brakes axon growth. Our results therefore provide a novel GAP that regulates axon growth and braking sequentially through Eph receptor-independent and Eph receptor-dependent pathways. [ABSTRACT FROM AUTHOR]

Chemoreceptor (also called methyl-accepting chemotaxis protein, MCP) is the leading signal protein in the chemotaxis signaling pathway. MCP senses and binds chemoeffectors, specifically, and transmits the sensed signal to downstream proteins of the chemotaxis signaling system. The genome of Agrobacterium fabrum (previously, tumefaciens) C58 predicts that a total of 20 genes can encode MCP, but only the MCP-encoding gene atu0514 is located inside the che operon. Hence, the identification of the exact function of atu0514-encoding chemoreceptor (here, named as MCP514) will be very important for us to understand more deeply the chemotaxis signal transduction mechanism of A. fabrum. The deletion of atu0514 significantly decreased the chemotactic migration of A. fabrum in a swim plate. The test of atu0514-deletion mutant (Δ514) chemotaxis toward single chemicals showed that the deficiency of MCP514 significantly weakened the chemotactic response of A. fabrum to four various chemicals, sucrose, valine, citric acid and acetosyringone (AS), but did not completely abolish the chemotactic response. MCP514 was localized at cell poles although it lacks a transmembrane (TM) region and is predicted to be a cytoplasmic chemoreceptor. The replacement of residue Phe328 showed that the helical structure in the hairpin subdomain of MCP514 is a direct determinant for the cellular localization of MCP514. Single respective replacements of key residues indicated that residues Asn336 and Val353 play a key role in maintaining the chemotactic function of MCP514. [ABSTRACT FROM AUTHOR]

With increasing concerns on the ecological risks of pollutants, many efforts have been devoted to revealing the toxic effects of pollutants on algae or bacteria in their monocultures. However, how pollutants affect algae and bacteria in their cocultures is still elusive but crucial due to its more environmental relevance. The present review outlines the interactions between algae and bacteria, reveals the influential mechanisms of pollutants (including pesticides, metals, engineered nanomaterials, pharmaceutical and personal care products, and aromatic pollutants) to algae and bacteria in their coexisted systems, and puts forward prospects for further advancing toxic studies in algal-bacterial systems. Pollutants affect the physiological and ecological functions of bacteria and algae by interfering with their relationships. Cell-to-cell adhesion, substrate exchange and biodegradation of organic pollutants, enhancement of signal transduction, and horizontal transfer of tolerance genes are important defense strategies in algal-bacterial systems to cope with pollution stress. Developing suitable algal-bacterial models, identifying cross-kingdom signaling molecules, and deciphering the horizontal transfer of pollutant resistant genes between algae and bacteria under pollution stress are the way forward to fully exploit the risks of pollutants in natural aquatic environments. [Display omitted] • Pollutants affect algae and bacteria by interfering algal-bacterial interactions. • Physical contact prevents contaminants from entering the cell. • Substrate exchange and signal transduction are disturbed by pollutants. • Horizontal gene transfer improves the tolerance of organisms to pollutants. • Future prospect for toxicity test based on algal-bacterial coexistent systems. [ABSTRACT FROM AUTHOR]

Abstract In most signal transduction systems, coupling or scaffold proteins establish crucial connections between receptors and histidine kinases. These connections are important for signal transduction. The bacterial chemotaxis system is a canonical signal transduction system that relies on coupling proteins. The coupling proteins in the chemotaxis system have two architectures: CheW or CheV. In a typical chemotaxis signal transduction system, two CheW coupling protein molecules bridge a histidine kinase CheA dimer and two chemoreceptor (also called as methyl-accepting chemotaxis protein, MCP) trimers of dimers to form a core signaling complex and couple CheA activity to chemoreceptor control. Although CheW is a small cytoplasmic protein, it plays multiple functions in chemotaxis. CheW also builds connections between core signaling complexes, which leads to the formation of large chemosensory arrays that are responsible for collecting and amplifying signals from various chemoreceptors. Another coupling protein, CheV, shares a largely redundant ability with CheW; however, the function of CheV is not identical to that of CheW in chemotaxis. In this article, we summarize the molecular mechanism of chemotaxis in Escherichia coli and review the recent advances in the structural details and functions of CheW and CheV. Furthermore, we focus on the diversity of coupling proteins and discuss the relationship among multiple coupling proteins in one organism. [ABSTRACT FROM AUTHOR]

Ca2+ is an essential nutrient for plants and animals which plays an important role in plant signal transduction. Although the function and regulation of mechanism of Ca2+ in alleviating various biotic and abiotic stresses in plants have been studied deeply, the molecular mechanism to adapt high Ca2+ stress is still unclear in cotton. In this study, 103 cotton accessions were germinated under 200 mM CaCl 2 stress, and two extremely Ca2+-resistant (Zhong 9807, R) and Ca2+-sensitive (CRI 50, S) genotypes were selected from 103 cotton accessions. The two accessions were then germinated for 5 days in 0 mM CaCl 2 and 200 mM CaCl 2 respectively, after which they were sampled for transcriptome sequencing. Morphological and physiological analyses suggested that PLR2 specifically expressed in R may enhance the ability of cotton to scavenge ROS by promoting the synthesis of SDG. In conclusion, this study proposed the adaptation mechanisms to response to the high Ca2+ stress in cotton which can contribute to improve the stress resistance of cotton. • CML (Calmodulin-like) proteins play a major role in signal transduction under high Ca2+ stress. • Interaction between CML and ABA (Abscisic acid) signaling pathway under high Ca2+ stress. • High Ca2+ stress promotes SDG (secoisolariciresinol) production in cotton. • SDG alleviates high Ca2+ stress by scavenging ROS. [ABSTRACT FROM AUTHOR]