Omics studies of DNA G-/C-quadruplexes in plants.

Genome-wide studies of DNA G- and C-quadruplexes (G4s and i-motifs, respectively) can boost the pace of progress towards a comprehensive understanding of their biological implications and practical applications in plants. We summarize the current state of knowledge about omics studies in order to highlight the current challenges and propose future directions to take studies of plant quadruplexes to the next step.

Homotherapy for heteropathy: Interleukin-41 and its biological functions.

Interleukin-41 (IL-41) is a newly discovered cytokine, named Cometin, Subfatin, meteorin-like transcription (Metrnl), and so forth. It is widely expressed in animals and can exert its biological roles through autocrine and paracrine forms. It has functions such as anti-inflammatory, improving body metabolism, regulating immunity, regulating fat metabolism and participates in the process of autoimmune disease or inflammatory injury. It plays an important role in psoriasis, diabetes, Crohn's disease (CD), osteoarthritis, Kawasaki disease (KD), Graves' disease, autoimmune hepatitis, infertility, obesity, sepsis, cardiovascular diseases and respiratory diseases. This paper reviews the biological functions of IL-41, the relationship between IL-41 and diseases, the effects of IL-41 in the cytokine network and the possible signalling pathways. In order to explore the same target or the same drug for the treatment of different diseases from the perspective of homotherapy for heteropathy, cytokine strategies based on IL-41 have been put forward for the precise treatment of immune diseases and inflammatory diseases. It is worth noting that IL-41 related preparations for lung protection and smoking cessation are interesting research fields.

Topological ranks reveal functional knowledge encoded in biological networks: a comparative analysis.

MOTIVATION: Biological networks topology yields important insights into biological function, occurrence of diseases and drug design. In the last few years, different types of topological measures have been introduced and applied to infer the biological relevance of network components/interactions, according to their position within the network structure. Although comparisons of such measures have been previously proposed, to what extent the topology per se may lead to the extraction of novel biological knowledge has never been critically examined nor formalized in the literature. RESULTS: We present a comparative analysis of nine outstanding topological measures, based on compact views obtained from the rank they induce on a given input biological network. The goal is to understand their ability in correctly positioning nodes/edges in the rank, according to the functional knowledge implicitly encoded in biological networks. To this aim, both internal and external (gold standard) validation criteria are taken into account, and six networks involving three different organisms (yeast, worm and human) are included in the comparison. The results show that a distinct handful of best-performing measures can be identified for each of the considered organisms, independently from the reference gold standard. AVAILABILITY: Input files and code for the computation of the considered topological measures and K-haus distance are available at https://gitlab.com/MaryBonomo/ranking. CONTACT: simona.rombo@unipa.it. SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online.

ARAP1-AS1: a novel long non-coding RNA with a vital regulatory role in human cancer development.

Long non-coding RNAs (lncRNAs) have garnered significant attention in biomedical research due to their pivotal roles in gene expression regulation and their association with various human diseases. Among these lncRNAs, ArfGAP With RhoGAP Domain, Ankyrin Repeat, And PH Domain 1 - Antisense RNA 1 (ARAP1-AS1) has recently emerged as an novel oncogenic player. ARAP1-AS1 is prominently overexpressed in numerous solid tumors and wields influence by modulating gene expression and signaling pathways. This regulatory impact is realized through dual mechanisms, involving both competitive interactions with microRNAs and direct protein binding. ARAP1-AS1 assumes an important role in driving tumorigenesis and malignant tumor progression, affecting biological characteristics such as tumor expansion and metastasis. This paper provides a concise review of the regulatory role of ARAP1-AS1 in malignant tumors and discuss its potential clinical applications as a biomarker and therapeutic target. We also address existing knowledge gaps and suggest avenues for future research. ARAP1-AS1 serves as a prototypical example within the burgeoning field of lncRNA studies, offering insights into the broader landscape of non-coding RNA molecules. This investigation enhances our comprehension of the complex mechanisms that govern the progression of cancer.

Clinical pathological significance and biological function of PLIN1 in hepatocellular carcinoma: bioinformatics analysis and in vitro experiments.

BACKGROUND & AIMS: Perilipin 1 (PLIN1) is an essential lipid droplet surface protein that participates in cell life activities by regulating energy balance and lipid metabolism. PLIN1 has been shown to be closely related to the development of numerous tumor types. The purpose of this work was to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and to investigate the underlying mechanisms involved. METHODS: Public high-throughput RNA microarray and RNA sequencing data were collected to examine PLIN1 levels and clinical significance in patients with HCC. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) were conducted to assess the expression levels and the clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressing PLIN1. CCK8 assay, wound healing assay, transwell assay, and flow cytometric analysis were conducted to explore the effects of PLIN1 overexpression on HCC cell proliferation, migration, invasion, and cell cycle distribution. Ultimately, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the underlying mechanisms of PLIN1 in HCC progression based on HCC differentially expressed genes and PLIN1 co-expressed genes. RESULTS: PLIN1 was markedly downregulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion of SK and Huh7 cells in vitro, as well as arresting the HCC cell cycle at the G0/G1 phase. More significantly, energy conversion-related biological processes, lipid metabolism, and cell cycle signalling pathways were the three most enriched molecular mechanisms. CONCLUSION: The present study revealed that PLIN1 downregulation is associated with poor prognosis in HCC patients and accelerated HCC progression by promoting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.

The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors.

Digestive tract tumors are heterogeneous and involve the dysregulation of multiple signaling pathways. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a notable role in the oncogenesis of digestive tract tumors. Typically activated by pro-inflammatory cytokines, it regulates important biological processes, such as cell growth, differentiation, apoptosis, immune responses, and inflammation. The aberrant activation of this pathway manifests in different forms, including mutations in JAKs, overexpression of cytokine receptors, and sustained STAT activation, and contributes to promoting the malignant characteristics of cancer cells, including uncontrolled proliferation, resistance to apoptosis, enhanced invasion and metastasis, angiogenesis, acquisition of stem-like properties, and drug resistance. Numerous studies have shown that aberrant activation of the JAK-STAT pathway is closely related to the development and progression of digestive tract tumors, contributing to tumor survival, angiogenesis, changes in the tumor microenvironment, and even immune escape processes. In addition, this signaling pathway also affects the sensitivity of digestive tract tumors to chemotherapy and targeted therapy. Therefore, it is crucial to comprehensively understand the oncogenic mechanisms underlying the JAK-STAT pathway in order to develop effective therapeutic strategies against digestive tract tumors. Currently, several JAK-STAT inhibitors are undergoing clinical and preclinical trials as potential treatments for various human diseases. However, further investigation is required to determine the role of this pathway, as well as the effectiveness and safety of its inhibitors, especially in the context of digestive tract tumors. In this review, we provide an overview of the structure, classic activation, and negative regulation of the JAK-STAT pathway. Furthermore, we discuss the pathogenic mechanisms of JAK-STAT signaling in different digestive tract tumors, with the aim of identifying potential novel therapeutic targets. Video Abstract.

Advances in the investigation of N6-isopentenyl adenosine i6A RNA modification.

Prenylation (isopentenylation), a key post-transcriptional modification with a hydrophobic prenyl group onto the biomacromolecules such as RNA and proteins, influences their localization and function. Prenyltransferases mediate this process, while cytokinin oxidases degrade the prenylated adenosine in plants. This review summarizes current progress in detecting prenylation modifications in RNA across species and their effects on protein synthesis. Advanced methods have been developed to label and study these modifications in vitro and in vivo, despite challenges posed by the inert chemical properties of prenyl groups. Continued advancements in bioorthogonal chemistry promise new tools for understanding the precise biological functions of prenylated RNA modifications and other related proteins.

DARS-AS1: A Vital Oncogenic LncRNA Regulator with Potential for Cancer Prognosis and Therapy.

DARS-AS1, short for Aspartyl-tRNA synthetase antisense RNA 1, has emerged as a pivotal player in cancers. Upregulation of this lncRNA is a recurrent phenomenon observed across various cancer types, where it predominantly assumes oncogenic roles, exerting influence on multiple facets of tumor cell biology. This aberrant expression of DARS-AS1 has triggered extensive research investigations, aiming to unravel its roles and clinical values in cancer. In this review, we elucidate the significant correlation between dysregulated DARS-AS1 expression and adverse survival prognoses in cancer patients, drawing from existing literature and pan-cancer analyses from The Cancer Genome Atlas (TCGA). Additionally, we provide comprehensive insights into the diverse functions of DARS-AS1 in various cancers. Our review encompasses the elucidation of the molecular mechanisms, ceRNA networks, functional mediators, and signaling pathways, as well as its involvement in therapy resistance, coupled with the latest advancements in DARS-AS1-related cancer research. These recent updates enrich our comprehensive comprehension of the pivotal role played by DARS-AS1 in cancer, thereby paving the way for future applications of DARS-AS1-targeted strategies in tumor prognosis evaluation and therapeutic interventions. This review furnishes valuable insights to advance the ongoing efforts in combating cancer effectively.

Why might animals remember? A functional framework for episodic memory research in comparative psychology.

One of Clayton's major contributions to our understanding of animal minds has been her work on episodic-like memory. A central reason for the success of this work was its focus on ecological validity: rather than looking for episodic memory for arbitrary stimuli in artificial contexts, focussing on contexts in which episodic memory would serve a biological function such as food caching. This review aims to deepen this insight by surveying the numerous functions that have been proposed for episodic memory, articulating a philosophically grounded framework for understanding what exactly functions are, and drawing on these to make suggestions for future directions in the comparative cognitive psychology of episodic memory. Our review suggests four key insights. First, episodic memory may have more than one function and may have different functions in different species. Second, cross-disciplinary work is key to developing a functional account of episodic memory. Third, there is scope for further theoretical elaboration of proposals relating episodic memory to food caching and, in particular, future-oriented cognition. Finally, learning-related functions suggested by AI (artificial intelligence)-based models are a fruitful avenue for future behavioural research.

Comparative Proteome Profiling of Extracellular Vesicles from Three Growth Phases of Haematococcus pluvialis under High Light and Sodium Acetate Stresses.

Extracellular vesicles (EVs) are nano-sized particles involved in intercellular communications that intrinsically possess many attributes as a modern drug delivery platform. Haematococcus pluvialis-derived EVs (HpEVs) can be potentially exploited as a high-value-added bioproduct during astaxanthin production. The encapsulation of HpEV cargo is a crucial key for the determination of their biological functions and therapeutic potentials. However, little is known about the composition of HpEVs, limiting insights into their biological properties and application characteristics. This study examined the protein composition of HpEVs from three growth phases of H. pluvialis grown under high light (350 µmol·m-2·s-1) and sodium acetate (45 mM) stresses. A total of 2038 proteins were identified, the majority of which were associated with biological processes including signal transduction, cell proliferation, cell metabolism, and the cell response to stress. Comparative analysis indicated that H. pluvialis cells sort variant proteins into HpEVs at different physiological states. It was revealed that HpEVs from the early growth stage of H. pluvialis contain more proteins associated with cellular functions involved in primary metabolite, cell division, and cellular energy metabolism, while HpEVs from the late growth stage of H. pluvialis were enriched in proteins involved in cell wall synthesis and secondary metabolism. This is the first study to report and compare the protein composition of HpEVs from different growth stages of H. pluvialis, providing important information on the development and production of functional microalgal-derived EVs.

Precision Sequence-Defined Polymers: From Sequencing to Biological Functions.

Precise sequence-defined polymers (SDPs) with uniform chain-to-chain structure including chain length, unit sequence, and end functionalities represent the pinnacle of sophistication in the realm of polymer science. For example, the absolute control over the unit sequence of SDPs allows for the bottom-up design of polymers with hierarchical microstructures and functions. Accompanied with the development of synthetic techniques towards precision SDPs, the decoding of SDP sequences and construction of advanced functions irreplaceable by other synthetic materials is of central importance. In this Minireview, we focus on recent advances in SDP sequencing techniques including tandem mass spectrometry (MS), chemically assisted primary MS, as well as other non-destructive sequencing methods such as nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), and nanopore sequencing. Additionally, we delve into the promising prospects of SDP functions in the area of cutting-edge biological research. Topics of exploration include gene delivery systems, the development of hybrid materials combining SDPs and nucleic acids, protein recognition and regulation, as well as the interplay between chirality and biological functions. A brief outlook towards the future directions of SDPs is also presented.

FYN: emerging biological roles and potential therapeutic targets in cancer.

Src family protein kinases (SFKs) play a key role in cell adhesion, invasion, proliferation, survival, apoptosis, and angiogenesis during tumor development. In humans, SFKs consists of eight family members with similar structure and function. There is a high level of overexpression or hyperactivity of SFKs in tumor, and they play an important role in multiple signaling pathways involved in tumorigenesis. FYN is a member of the SFKs that regulate normal cellular processes. Additionally, FYN is highly expressed in many cancers and promotes cancer growth and metastasis through diverse biological functions such as cell growth, apoptosis, and motility migration, as well as the development of drug resistance in many tumors. Moreover, FYN is involved in the regulation of multiple cancer-related signaling pathways, including interactions with ERK, COX-2, STAT5, MET and AKT. FYN is therefore an attractive therapeutic target for various tumor types, and suppressing FYN can improve the prognosis and prolong the life of patients. The purpose of this review is to provide an overview of FYN's structure, expression, upstream regulators, downstream substrate molecules, and biological functions in tumors.

Encapsulation of cinnamaldehyde: an insight on delivery systems and food applications.

Cinnamaldehyde is an essential oil extracted from the leaves, bark, roots and flowers of cinnamon plants (genus Cinnamomum). Cinnamaldehyde has shown biological functions such as antioxidants, antimicrobials, anti-diabetic, anti-obesity and anti-cancer. However, poor solubility in water as well as molecular sensitivity to oxygen, light, and high temperature limit the direct application of cinnamaldehyde. Researchers are using different encapsulation techniques to maximize the potential biological functions of cinnamaldehyde. Different delivery systems such as liposomes, emulsions, biopolymer nanoparticles, complex coacervation, molecular inclusion, and spray drying have been developed for this purpose. The particle size and morphology, composition and physicochemical properties influence the performance of each delivery system. Consequently, the individual delivery system has its advantages and limitations for specific applications. Given the essential role of cinnamaldehyde in functional food and food preservation, appropriate approaches should be applied in the encapsulation and application of encapsulated cinnamaldehyde. This review systematically analyzes available encapsulation techniques for cinnamaldehyde in terms of their design, properties, advantages and limitations, and food application status. The information provided in this manuscript will assist in the development and widespread use of cinnamaldehyde-loaded particles in the food and beverage industries.

High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma.

Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.

The biogenesis, biological functions and modification of Circular RNAs.

Circular RNAs are covalently closed and non-coding in eukaryotes, which have tissue- specific and temporal-specific expression patterns whose biogenesis is regulated by transcription and splicing. Most circular RNAs are localized in the cytoplasm. The sequences and protein-binding elements of circular RNAs facilitate circular RNAs in exerting biological functions through complementary base pairing, regulating protein function or self-translation. Recent studies have revealed that N6-Methyladenosine (m6A), a prevalent post-transcriptional modification, can affect the translation, localization, and degradation of circular RNAs. Cutting-edge research into circular RNAs have benefitted from the development of high-throughput sequencing technology. Furthermore, the expansion of novel research methods has promoted progress into circular RNA research.

Insight into crustacean cathepsins: Structure-evolutionary relationships and functional roles in physiological processes.

Cathepsins belong to a group of proteins that are present in both prokaryotic and eukaryotic organisms and have an extremely high degree of evolutionary conservation. These proteins are functionally active in extracellular environments as soluble enzymatic proteins or attached to plasma membrane receptors. In addition, they occur in cellular secretory vesicles, mitochondria, the cytosol, and within the nuclei of eukaryotic cells. Cathepsins are classified into various groups based on their sequence variations, leading to their structural and functional diversification. The molecular understanding of the physiology of crustaceans has shown that proteases, including cathepsins, are expressed ubiquitously. They also contain one of the central regulatory systems for crustacean reproduction, growth, and immune responses. This review focuses on various aspects of the crustaceans cathepsins and emphasizes their biological roles in different physiological processes such as reproduction, growth, development, and immune responses. We also describe the bioactivity of crustaceans cathepsins. Because of the vital biological roles that cathepsins play as cellular proteases in physiological processes, they have been proposed as potential novel targets for the development of management strategies for the aquaculture industries.

Functional characterization of differentially expressed proteins coming from unisexual and bisexual infected Schistosoma japonicum female worms.

Schistosomiasis is an important zoonotic disease affecting up to 40 kinds of animals and is responsible for ∼250 million human cases per year. Due to the extensive use of praziquantel for the treatment of parasitic diseases, drug resistance has been reported. Consequently, novel drugs and effective vaccines are urgently needed for sustained control of schistosomiasis. Targeting reproductive development of Schistosoma japonicum could contribute to the control of schistosomiasis. In this study, five highly expressed proteins (S. japonicum large subunit ribosomal protein L7e, S. japonicum glutathione S-transferase class-mu 26 kDa isozyme, S. japonicum UDP-galactose-4-epimerase and two hypothetical proteins SjCAX70849 and SjCAX72486) in 18, 21, 23, and 25-day mature female worms compared to single-sex infected female worms were selected based on our previous proteomic analysis. Quantitative real-time polymerase chain reaction analysis and long-term interference with small interfering RNA were performed to identify the biological functions of these five proteins. The transcriptional profiles suggested that all five proteins participated in the maturation of S. japonicum. RNA interference against these proteins resulted in morphological changes to S. japonicum. The results of an immunoprotection assay revealed that immunization of mice with recombinant SjUL-30 and SjCAX72486 upregulated production of immunoglobulin G-specific antibodies. Collectively, the results demonstrated that these five differentially expressed proteins were vital to reproduction of S. japonicum and, thus, are potential candidate antigens for immune protection against schistosomiasis.

Proteomic approach-based comparison of metabolic pathways and functional activities of whey proteins derived from Guishan and Saanen goat milk.

Guishan goats, a unique goat breed in Yunnan Province, have a long history and representation, but their whey protein and function remain unclear. In this study, we carried out a quantitative analysis of the Guishan and Saanen goat whey proteome using a label-free proteomic approach. A total of 500 proteins were quantified from the 2 kinds of goat whey proteins, including 463 common proteins, 37 uniquely expressed whey proteins (UEWP), and 12 differentially expressed whey proteins (DEWP). Bioinformatics analysis indicated that UEWP and DEWP were mainly involved in cellular and immune system processes, membrane, and binding. In addition, UEWP and DEWP in Guishan goats participated primarily in metabolism and immune-related pathways, whereas Saanen goat whey proteins were associated mostly with environmental information processing-related pathways. Guishan goat whey promoted the growth of RAW264.7 macrophages more than Saanen goat whey, and significantly reduced the production of nitric oxide in lipopolysaccharide-stimulated RAW264.7 cells. This study provides a reference for further understanding these 2 goat whey proteins and finding functional active substances from them.

Gelsolin, an Actin-Binding Protein: Bioinformatic Analysis and Functional Significance in Urothelial Bladder Carcinoma.

The involvement of the actin-regulatory protein, gelsolin (GSN), in neoplastic transformation has been reported in different cancers including bladder cancer. However, the exact mechanism by which GSN influences bladder cancer development is not well understood. Here, we sought to reveal the functional significance of GSN in bladder cancer by undertaking a comprehensive bioinformatic analysis of TCGA datasets and through the assessment of multiple biological functions. GSN expression was knocked down in bladder cancer cell lines with two siRNA isoforms targeting GSN. Proliferation, migration, cell cycle and apoptosis assays were carried out. GSN expression, enrichment analysis, protein-protein interaction and immune infiltration analysis were verified through online TCGA tools. The data indicated that GSN expression is associated with bladder cancer proliferation, migration and enhanced cell apoptosis through regulation of NF-κB expression. GSN expression correlated with various inflammatory cells and may influence the immunity of the tumor microenvironment. Computational analysis identified several interacting partners which are associated with cancer progression and patient outcome. The present results demonstrate that GSN plays an important role in bladder cancer pathogenesis and may serve as a potential biomarker and therapeutic target for cancer therapy.

Exploring the Role of the Plant Actin Cytoskeleton: From Signaling to Cellular Functions.

The plant actin cytoskeleton is characterized by the basic properties of dynamic array, which plays a central role in numerous conserved processes that are required for diverse cellular functions. Here, we focus on how actins and actin-related proteins (ARPs), which represent two classical branches of a greatly diverse superfamily of ATPases, are involved in fundamental functions underlying signal regulation of plant growth and development. Moreover, we review the structure, assembly dynamics, and biological functions of filamentous actin (F-actin) from a molecular perspective. The various accessory proteins known as actin-binding proteins (ABPs) partner with F-actin to finely tune actin dynamics, often in response to various cell signaling pathways. Our understanding of the significance of the actin cytoskeleton in vital cellular activities has been furthered by comparison of conserved functions of actin filaments across different species combined with advanced microscopic techniques and experimental methods. We discuss the current model of the plant actin cytoskeleton, followed by examples of the signaling mechanisms under the supervision of F-actin related to cell morphogenesis, polar growth, and cytoplasmic streaming. Determination of the theoretical basis of how the cytoskeleton works is important in itself and is beneficial to future applications aimed at improving crop biomass and production efficiency.