Comprehensive analysis of phospholipid in milk and their biological roles as nutrients and biomarkers.

Phospholipids (PL) have garnered significant attention due to their physiological activities. Milk and other dairy products are important dietary sources for humans and have been extensively used to analyze the presence of PL by various analytical techniques. In this paper, the analysis techniques of PL were reviewed with the eight trigrams of phospholipidomics and a comprehensive fingerprint of 1295 PLs covering 8 subclasses in milk and other dairy products, especially. Technology is the primary productive force. Based on phospholipidomics technology, we further review the relationship between the composition of PL and factors that may be involved in processing and experimental operation, and emphasized the significance of the biological role played by PL in dietary supplements and biomarkers (production, processing and clinical research), and providing the future research directions.

Comparative clinical significance and biological roles of PFKFB family members in oral squamous cell carcinoma.

BACKGROUND: Cancer cells promote glycolysis, which supports rapid cell growth and proliferation. Phosphofructokinase-fructose bisphosphatases (PFKFBs), a family of bidirectional glycolytic enzymes, play key roles in the regulation of glycolysis in many types of cancer. However, their roles in oral squamous cell carcinoma (OSCC), the most common type of oral cancer, are still unknown. METHODS: We compared the gene expression levels of PFKFB family members and analyzed their clinical significance in oral cancer patients, whose clinical data were obtained the Cancer Genome Atlas database. Moreover, real-time quantitative polymerase chain reaction, western blotting, assays for cell viability, cell cycle, cell migration and viability of cell spheroid were performed in scramble and PFKFB-silenced cells. RESULTS: We discovered that PFKFB3 expression in tumor tissues was slightly higher than that in tumor adjacent normal tissues but that PFKFB4 expression was significantly higher in the tumor tissues of oral cancer patients. High PFKFB3 and PFKFB4 expression had different effects on the prognosis of oral cancer patients with different clinicopathological outcomes. Our data showed that PFKFB3 and PFKFB4 play different roles; PFKFB3 is involved in cell viability, G2/M cell cycle progression, invasion, and migration, whereas PFKFB4 is involved in the drug resistance and cancer stemness of OSCC cells. Furthermore, oral cancer patients with co-expressions of PFKFB3/cell cycle or EMT markers and PFKFB4/stemness markers had poor prognosis. CONCLUSIONS: PFKFB3 and PFKFB4 play different biological roles in OSCC cells, which implying that they might be potential prognostic biomarkers for OSCC patients with certain clinicopathological outcomes.

The game of models: Dietary reconstruction in human evolution.

Despite substantial additions to the paleontological record and unanticipated improvements in analytical techniques since the Journal of Human Evolution was first published, consensus on the diet of early hominin species remains elusive. For instance, the notable advances in the analyses of hominin dental microwear and stable isotopes have provided a plethora of data that have in some instances clouded what was once ostensibly a clear picture of dietary differentiation between and within hominin taxa. In the present study, we explore the reasons why the retrodiction of diet in human evolution has proven vexing over the last half century from the perspective of both ecological and functional-mechanical models. Such models continue to be indispensable for paleobiological reconstructions, but they often contain rigid or unstated assumptions about how primary paleontological data, such as fossils and their geological and taphonomic contexts, allow unambiguous insight into the evolutionary processes that produced them. In theoretical discussions of paleobiology, it has long been recognized that a mapping function of morphology to adaptation is not one-to-one, in the sense that a particular trait cannot necessarily be attributed to a specific selective pressure and/or behavior. This article explores how the intrinsic variability within biological systems has often been underappreciated in paleoanthropological research. For instance, to claim that derived anatomical traits represent adaptations related to stereotypical behaviors largely ignores the importance of biological roles (i.e., how anatomical traits function in the environment), a concept that depends on behavioral flexibility for its potency. Similarly, in the paleoecological context, the underrepresentation of variability within the 'edible landscapes' our hominin ancestors occupied has inhibited an adequate appreciation of early hominin dietary flexibility. Incorporating the reality of variation at organismal and ecological scales makes the practice of paleobiological reconstruction more challenging, but in return, allows for a better appreciation of the evolutionary possibilities that were open to early hominins.

Functions and underlying mechanisms of miR-650 in human cancers.

MicroRNAs (miRNAs) are one type of noncoding RNAs that interfere with mRNA translation to downregulate gene expression, which results in posttranscriptional gene silencing. Over the past two decades, miRNAs have been widely reported to impact the progression of malignant tumours by interfering with cancer initiation and progression; therefore, miRNAs represent potential new diagnostic and therapeutic tools. miR-650 is a newly identified miR, and increasing studies have demonstrated that miR-650 plays critical roles in cancer progression, such as mediating the Wnt signalling pathway/AXIN1 (axis inhibition protein 1) axis in hepatocellular carcinoma. Nevertheless, associations between the expression patterns and molecular mechanisms of miR-650 in cancer have not been comprehensively described. In this article, we review the existing evidence regarding the mechanisms by which miR-650 expression is altered and their relation to cancer. Moreover, the promising clinical application of miR-650 for diagnosis and treatment is highlighted.

Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets.

TWIK-related acid-sensitive K+ (TASK) channels, including TASK-1, TASK-3, and TASK-5, are important members of the two-pore domain potassium (K2P) channel family. TASK-5 is not functionally expressed in the recombinant system. TASK channels are very sensitive to changes in extracellular pH and are active during all membrane potential periods. They are similar to other K2P channels in that they can create and use background-leaked potassium currents to stabilize resting membrane conductance and repolarize the action potential of excitable cells. TASK channels are expressed in both the nervous system and peripheral tissues, including excitable and non-excitable cells, and are widely engaged in pathophysiological phenomena, such as respiratory stimulation, pulmonary hypertension, arrhythmia, aldosterone secretion, cancers, anesthesia, neurological disorders, glucose homeostasis, and visual sensitivity. Therefore, they are important targets for innovative drug development. In this review, we emphasized the recent advances in our understanding of the biophysical properties, gating profiles, and biological roles of TASK channels. Given the different localization ranges and biologically relevant functions of TASK-1 and TASK-3 channels, the development of compounds that selectively target TASK-1 and TASK-3 channels is also summarized based on data reported in the literature.

Biological roles of glycans.

Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences.

[Biological role of heterogeneous glycoprotein structures]. / A heterogén glikoproteinszerkezetek biológiai szerepe.

Carbohydrate molecules connected mostly with covalent junctions to protein chains are called glycoproteins. These carbohydrate molecules are attached to the protein core in different qualities and order. When the protein core is connected with acidic components such as uronic acid or SO4 radicals, they are called proteoglycans. The currently used name "glycosaminoglycan" in this case is not entirely correct. In the living world polymannane structures occur, too. Glycoproteins do not only exceptionally hold acidic groups but they have neuraminic acid derivatives. Tissue, cellular and matrix structures, and mostly all serum "proteins" are mainly glycoproteins. In the everyday clinical practice glycoproteins are mentioned as proteins. Nevertheless, the inadequate use of the concept may cause errors in the attitudes, too. This paper aims to correct this notion, because the term of "glycobiology" has already been expanded to be an independent scientific field. The practical clinical consequences of recent knowledge in this field are also summarized including novel findings on glycoprotein structures and functions. The importance of the quantity of carbohydrates, and their structural arrangements are also presented. In short, significance of glycoprotein-carbohydrate structures, as well as their physiological and pathological roles are reviewed in order to introduce the field of "glycobiology". Orosomucoid and immunoglobulins are discussed separately. Orv. Hetil., 2016, 157(30), 1185-1192.

LINK-A: unveiling its functional role and clinical significance in human tumors.

LINK-A, also recognized as LINC01139, has emerged as a key oncological lncRNA in cancer. LINK-A is upregulated in solid and liquid tumor samples, including breast cancer, ovarian cancer, glioma, non-small-cell lung cancer, and mantle cell lymphoma. Notably, LINK-A is involved in regulating critical cancer-related pathways, such as AKT and HIF1α signaling, and is implicated in a range of oncogenic activities, including cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), cell invasion and migration, and glycolysis reprogramming. LINK-A's differential expression and its correlation with clinical features enable it to be a promising biomarker for cancer diagnosis, prognosis, and the stratification of tumor progression. Additionally, LINK-A's contribution to the development of resistance to cancer therapies, including AKT inhibitors and immunotherapy, underscores its potential as a therapeutic target. This review provides a comprehensive overview of the available data on LINK-A, focusing on its molecular regulatory pathways and clinical significance. By exploring the multifaceted nature of LINK-A in cancer, the review aims to offer a valuable resource for future research directions, potentially guiding the development of novel therapeutic strategies targeting this lncRNA in cancer treatment.

The molecular structure, biological roles, and inhibition of plant pathogenic fungal chitin deacetylases.

Chitin/polysaccharide deacetylases belong to the carbohydrate esterases family 4 (CE4 enzymes). They play a crucial role in modifying the physiochemical characteristics of structural polysaccharides and are also involved in a wide range of biological processes such as fungal autolysis, spore formation, cell wall formation and integrity, and germling adhesion. These enzymes are mostly common in fungi, marine bacteria, and a limited number of insects. They facilitate the deacetylation of chitin which is a structural biopolymer that is abundantly found in fungal cell walls and spores and also in the cuticle and peritrophic matrices of insects. The deacetylases exhibit specificity towards a substrate containing a sequence of four GlcNAc units, with one of these units being subjected to deacetylation. Chitin deacetylation results in the formation of chitosan, which is a poor substrate for host plant chitinases, therefore it can suppress the host immune response triggered by fungal pathogens and enhance pathogen virulence and colonization. This review discusses plant pathogenic fungal chitin/polysaccharide deacetylases including their structure, substrate specificity, biological roles and some recently discovered chitin deacetylase inhibitors that can help to mitigate plant fungal diseases. This review provides fundamental knowledge that will undoubtedly lead to the rational design of novel inhibitors that target pathogenic fungal chitin deacetylases, which will also aid in the management of plant diseases, thereby safeguarding global food security.

The structure, biosynthesis, and biological roles of fetuin-A: A review.

Fetuin-A is a heterodimeric plasma glycoprotein containing an A-chain of 282 amino acids and a B-chain of 27 amino acid residues linked by a single inter-disulfide bond. It is predominantly expressed in embryonic cells and adult hepatocytes, and to a lesser extent in adipocytes and monocytes. Fetuin-A binds with a plethora of receptors and exhibits multifaceted physiological and pathological functions. It is involved in the regulation of calcium metabolism, osteogenesis, and the insulin signaling pathway. It also acts as an ectopic calcification inhibitor, protease inhibitor, inflammatory mediator, anti-inflammatory partner, atherogenic factor, and adipogenic factor, among other several moonlighting functions. Fetuin-A has also been demonstrated to play a crucial role in the pathogenesis of several disorders. This review mainly focuses on the structure, synthesis, and biological roles of fetuin-A. Information was gathered manually from various journals via electronic searches using PubMed, Google Scholar, HINARI, and Cochrane Library from inception to 2022. Studies written in English and cohort, case-control, cross-sectional, or experimental studies were considered in the review, otherwise excluded.

The Biological Roles of Urea: A Review of Preclinical Studies.

Urea is an organic compound that has been reported to be effective against many pathological conditions. However, many other studies have reported the toxic effects of urea. These controversies on the biological roles of urea remain unresolved. This review aims to evaluate the biological roles of urea in experimental animals from data published in peer-reviewed journals. A PubMed search was conducted using the phrase, "urea application in experimental animals." A total of 13 publications that met the inclusion criteria were evaluated. The test substance, animal model, number of animals, doses, duration of treatment, and effects were recorded. Regarding the toxic effect, urea caused decreased excretion of other nitrogenous compounds, increased oxidative stress, decreased insulin, and impairment of beta-cell glycolysis. Furthermore, it caused endothelial dysfunction, loss of synapsis, and decreased olfaction. Regarding the therapeutic effects, urea caused increased growth, increased digestion, and decreased hepatic dysfunction. It also induced apoptosis of tumor cells and exerted neuroprotective properties. Products containing urea should be used with caution, especially in individuals with symptoms of chronic kidney disease. However, more studies are needed to elucidate the mechanisms of its therapeutic effects.

The Biological and Molecular Function of LINC00665 in Human Cancers.

Long non-coding RNAs (lncRNAs) are more than 200 nucleotides in length and are implicated in the development of human cancers, without protein-coding function. Mounting evidence indicates that cancer initiation and progression are triggered by lncRNA dysregulation. Recently, a growing number of studies have found that LINC00665, a long intergenic non-protein coding RNA, may be associated with various cancers, including gastrointestinal tumors, gynecological tumors, and respiratory neoplasms. LINC00665 was reported to be significantly dysregulated in cancers and has an important clinical association. It participates in cell proliferation, migration, invasion, and apoptosis through different biological pathways. In this review, we summarize the current findings on LINC00665, including its biological roles and molecular mechanisms in various cancers. LINC00665 may be a potential prognostic biomarker and novel therapeutic target for cancers.

Selenium Nanoparticles as a Natural Antioxidant and Metabolic Regulator in Aquaculture: A Review.

Balanced aquafeed is the key factor for enhancing the productivity of aquatic animals. In this context, aquatic animals require optimal amounts of lipids, proteins, carbohydrates, vitamins, and minerals. The original plant and animals' ingredients in the basal diets are insufficient to provide aquafeed with suitable amounts of minerals. Concurrently, elements should be incorporated in aquafeed in optimal doses, which differ based on the basal diets' species, age, size, and composition. Selenium is one of the essential trace elements involved in various metabolic, biological, and physiological functions. Se acts as a precursor for antioxidative enzyme synthesis leading to high total antioxidative capacity. Further, Se can enhance the immune response and the tolerance of aquatic animals to infectious diseases. Several metabolic mechanisms, such as thyroid hormone production, cytokine formation, fecundity, and DNA synthesis, require sufficient Se addition. The recent progress in the nanotechnology industry is also applied in the production of Se nanoparticles. Indeed, Se nanoparticles are elaborated as more soluble and bioavailable than the organic and non-organic forms. In aquaculture, multiple investigations have elaborated the role of Se nanoparticles on the performances and wellbeing of aquatic animals. In this review, the outputs of recent studies associated with the role of Se nanoparticles on aquatic animals' performances were simplified and presented for more research and development.

Nep1-like Proteins from Valsa mali Differentially Regulate Pathogen Virulence and Response to Abiotic Stresses.

Necrosis and ethylene-inducing peptide 1(Nep1)-like protein (NLP) is well known for its cytotoxicity and immunogenicity on dicotyledonous, and it has attracted large attention due to its gene expansion and functional diversification in numerous phytopathogens. Here, two NLP family proteins, VmNLP1 and VmNLP2, were identified in the pathogenic fungus Valsa mali. We showed that VmNLP2 but not VmNLP1 induced cell death when transiently expressed in Nicotiana benthamiana. VmNLP2 was also shown to induce cell death in apple leaves via the treatment of the Escherichia coli-produced recombinant protein. VmNLP1 and VmNLP2 transcripts were drastically induced at the early stage of V. mali infection, whereas only VmNLP2 was shown to be essential for pathogen virulence. We also found that VmNLP1 and VmNLP2 are required for maintaining the integrity of cell membranes, and they differentially contribute to V. mali tolerance to salt- and osmo-stresses. Notably, multiple sequence alignment revealed that the second histidine (H) among the conserved heptapeptide (GHRHDWE) of VmNLP2 is mutated to tyrosine (Y). When this tyrosine (Y) was substituted by histidine (H), the variant displayed enhanced cytotoxicity in N. benthamiana, as well as enhanced virulence on apple leaves, suggesting that the virulence role of VmNLP2 probably correlates to its cytotoxicity activity. We further showed that the peptide among VmNLP2, called nlp25 (VmNLP2), triggered strong immune response in Arabidopsis thaliana. This work demonstrates that NLPs from V. mali involve multiple biological roles, and shed new light on how intricately complex the functions of NLP might be.

The biological and diagnostic roles of MicroRNAs in meningiomas.

MicroRNAs (miRNAs) refer to a class of small endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level. Emerging studies have shown that miRNAs play critical roles in tumorigenesis and cancer progression. However, roles and mechanisms of miRNA dysregulation in the pathogenesis of meningioma are not fully understood. Here, we first reviewed existing research of aberrantly expressed miRNAs identified by high throughput microarray profiling in meningioma. We also explored the potential of miRNA as biomarkers and therapeutic targets for novel treatment paradigms of meningiomas. In addition, we summarized recent researches that focused on the possible mechanisms involved in miRNA-mediate meningioma occurrence and progression. This review provides an overview of miRNA deregulation in meningioma and indicates the potential of miRNAs to be used as biomarkers or novel therapeutic targets.

Extracellular Vesicles: An Overlooked Secretion System in Cyanobacteria.

In bacteria, the active transport of material from the interior to the exterior of the cell, or secretion, represents a very important mechanism of adaptation to the surrounding environment. The secretion of various types of biomolecules is mediated by a series of multiprotein complexes that cross the bacterial membrane(s), each complex dedicated to the secretion of specific substrates. In addition, biological material may also be released from the bacterial cell in the form of vesicles. Extracellular vesicles (EVs) are bilayered, nanoscale structures, derived from the bacterial cell envelope, which contain membrane components as well as soluble products. In cyanobacteria, the knowledge regarding EVs is lagging far behind compared to what is known about, for example, other Gram-negative bacteria. Here, we present a summary of the most important findings regarding EVs in Gram-negative bacteria, discussing aspects of their composition, formation processes and biological roles, and highlighting a number of technological applications tested. This lays the groundwork to raise awareness that the release of EVs by cyanobacteria likely represents an important, and yet highly disregarded, survival strategy. Furthermore, we hope to motivate future studies that can further elucidate the role of EVs in cyanobacterial cell biology and physiology.

Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma.

Glioma is the most common type of intracranial malignant tumor, with a great recurrence rate due to its infiltrative growth, treatment resistance, intra- and intertumoral genetic heterogeneity. Recently, accumulating studies have illustrated that activated aerobic glycolysis participated in various cellular and clinical activities of glioma, thus influencing the efficacy of radiotherapy and chemotherapy. However, the glycolytic process is too complicated and ambiguous to serve as a novel therapy for glioma. In this review, we generalized the implication of key enzymes, glucose transporters (GLUTs), signalings and transcription factors in the glycolytic process of glioma. In addition, we summarized therapeutic interventions via the above aspects and discussed promising clinical applications for glioma.

Clinical significance and biological roles of small nucleolar RNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is among the most common and fatal cancers. It is a multistage and multifactorial carcinoma, in which a number of factors serve roles in its initiation and progression. Small nucleolar RNAs (snoRNAs), considered to serve a role in various cancers, have recently been identified to have significant contributions to HCC tumorigenesis. Recent studies suggest that snoRNAs have a critical role in the pathogenesis of HCC. Moreover, detailed studies have demonstrated that various snoRNAs are involved in a range of biological processes associated with HCC, including initiation, proliferation, tumor growth, the cell cycle, apoptosis and metastasis. In the present review, an overview of recent studies to date has been provided, focusing on the association of snoRNAs with HCC. Based on the findings, further studies focusing on the association of snoRNAs with HCC are required to verify the diagnostic and therapeutic capacities of snoRNAs in HCC.

Present Scenario of Long Non-Coding RNAs in Plants.

Small non-coding RNAs have been extensively studied in plants over the last decade. In contrast, genome-wide identification of plant long non-coding RNAs (lncRNAs) has recently gained momentum. LncRNAs are now being recognized as important players in gene regulation, and their potent regulatory roles are being studied comprehensively in eukaryotes. LncRNAs were first reported in humans in 1992. Since then, research in animals, particularly in humans, has rapidly progressed, and a vast amount of data has been generated, collected, and organized using computational approaches. Additionally, numerous studies have been conducted to understand the roles of these long RNA species in several diseases. However, the status of lncRNA investigation in plants lags behind that in animals (especially humans). Efforts are being made in this direction using computational tools and high-throughput sequencing technologies, such as the lncRNA microarray technique, RNA-sequencing (RNA-seq), RNA capture sequencing, (RNA CaptureSeq), etc. Given the current scenario, significant amounts of data have been produced regarding plant lncRNAs, and this amount is likely to increase in the subsequent years. In this review we have documented brief information about lncRNAs and their status of research in plants, along with the plant-specific resources/databases for information retrieval on lncRNAs.

Natural alkaloids: basic aspects, biological roles, and future perspectives.

Natural products have gained popularity worldwide for promoting healthcare, as well as disease prevention. Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation, antibacterial, antiviral, insecticidal, and antimetastatic effects on various types of cancers both in vitro and in vivo. This paper focuses on the naturally-derived alkaloids such as berberine, matrine, piperine, fritillarine, and rhynchophylline, etc., and summarizes the action mechanisms of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as drugs is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made. Following this, it is hoped that as a result of this review, there will be a greater awareness of the excellent promise that natural alkaloids show for use in the therapy of diseases.