Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer.

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Advances in transdermal siRNAs delivery: A review of current research progress.

Small interfering RNA (siRNAs) is a double-stranded RNA molecule which can hybridize with a specific mRNA sequence and block the translation of numerous genes to regulate endogenous genes and to defend the genome from invasive nucleic acids. The use of siRNAs has been studied as a treatment option for various skin conditions. One of the main obstacles in the dermal or transdermal delivery of this compound is low skin permeability, and application is limited by its negative charge, high polarity, susceptibility to degradation by nucleases, and difficulty in penetrating the skin barrier. Effective delivery of therapeutic biomolecules to their target is a challenging issue, which can be solved by innovations in drug delivery systems and lead to improvement of the efficiency of many new biopharmaceuticals. Designing of novel transdermal delivery systems garnered tremendous attention in both cosmeceutical and pharmaceutical research and industries, which offers a number of advantages. Developing safe and efficient siRNAs delivery vectors is essential for effective treatment of skin diseases. In recent years, significant progress has been made in the creation of delivery systems using lipids, polymers, cell-penetrating peptides, nanoparticles and other biologically active agents. In this review we will focus on the recent advancements in transdermal siRNAs delivery vectors, such as liposomes, dendrimers, cell-penetrating peptides, and spherical nucleic acid nanoparticles.

Regulation and mechanism of action of miRNAs on insulin resistance in skeletal muscles.

The term "insulin resistance" is commonly understood as a decrease in the response of insulin-sensitive tissues to insulin at its sufficient concentration, leading to chronic compensatory hyperinsulinemia. Type 2 diabetes mellitus is based on mechanisms consisting in the development of resistance to insulin in target cells (hepatocytes, adipocytes, skeletal muscle cells), resulting in the termination of an adequate response of these tissues to interaction with insulin. Since in healthy people 75-80% of glucose is utilized by skeletal muscle, it is more likely that the main cause of insulin resistance is impaired insulin-stimulated glucose utilization by skeletal muscle. With insulin resistance, skeletal muscles do not respond to insulin at its normal concentration, thereby determining an increase in glucose levels and a compensatory increase in insulin production in response to this. Despite many years of studying diabetes mellitus (DM) and insulin resistance, the molecular genetic basis for the development of these pathological conditions is still the subject of numerous studies. Recent studies point to the involvement of microRNAs (miRNAs) as dynamic modifiers in the pathogenesis of various diseases. MiRNAs are a separate class of RNA molecules that play a key role in the post-transcriptional regulation of gene expression. Recent studies have shown that miRNAs dysregulation in DM is closely related to miRNAs regulatory abilities in skeletal muscle insulin resistance. This gave grounds to consider an increase or decrease in the expression of individual microRNAs in muscle tissue and consider them as new biomarkers for diagnosing and monitoring insulin resistance and promising directions for targeted therapy. This review presents the results of scientific studies examining the role of miRNAs in skeletal muscle insulin resistance.

Studies on the role of non-coding RNAs in controlling the activity of T cells in asthma.

Bronchial asthma, commonly known as asthma, is a chronic inflammatory disease characterized by airway inflammation, increased responsiveness and changes in airway structure. T cells, particularly T helper cells, play a crucial role in the disease. Non-coding RNAs, which are RNAs that do not code for proteins, mainly include microRNAs, long non-coding RNAs, and circular RNAs, play a role in regulating various biological processes. Studies have shown that non-coding RNAs have an important role in the activation and transformation of T cells and other biological processes in asthma. The specific mechanisms and clinical applications are worth further examination. This article reviews the recent research on the role of microRNAs, long non-coding RNAs and circular RNAs in T cells in asthma.

The role of long non-coding RNAs in the development of adipose cells.

In recent times, the rising prevalence of obesity and its associated comorbidities have had a severe impact on human health and social progress. Therefore, scientists are delving deeper into the pathogenesis of obesity, exploring the role of non-coding RNAs. Long non-coding RNAs (lncRNAs), once regarded as mere "noise" during genome transcription, have now been confirmed through numerous studies to regulate gene expression and contribute to the occurrence and progression of several human diseases. LncRNAs can interact with protein, DNA, and RNA, respectively, and participate in regulating gene expression by modulating the levels of visible modification, transcription, post-transcription, and biological environment. Increasingly, researchers have established the involvement of lncRNAs in regulating adipogenesis, development, and energy metabolism of adipose tissue (white and brown fat). In this article, we present a literature review of the role of lncRNAs in the development of adipose cells.

Long non-coding RNAs as promising biomarkers and therapeutic targets in cervical cancer.

Cervical cancer is the second most common cancer in women. The detection of oncopathologies in the early stages of development is a paramount task of modern medicine, which can be solved only by improving modern diagnostic methods. The use of screening for certain tumor markers could complement modern tests such as testing for oncogenic types of human papillomavirus (HPV), cytology, colposcopy with acetic acid and iodine solutions. Such highly informative biomarkers can be long noncoding RNAs (lncRNAs) that are highly specific compared to the mRNA profile and are involved in the regulation of gene expression. LncRNAs are a class of non-coding RNAs molecules that are typically over 200 nucleotides in length. LncRNAs may be involved in the regulation of all major cellular processes, including proliferation and differentiation, metabolism, signaling pathways, and apoptosis. LncRNAs molecules are highly stable due to their small size, which is also their undoubted advantage. The study of individual lncRNAs as regulators of the expression of genes involved in the mechanisms of oncogenesis cervical cancer can be not only of great diagnostic value, but, as a result, of therapeutic significance in cervical cancer patients. This review article will present the characteristics of lncRNAs that allow them to be used as accurate diagnostic and prognostic tools, as well as to consider them as effective therapeutic targets in cervical cancer.

The role of long non-coding RNAs in carbohydrate and fat metabolism in the liver.

The metabolism of carbohydrates and lipids (fat) in the liver is closely interconnected both in physiological conditions and in pathology. This relationship in the body is possible due to the regulation by many factors, including epigenetic ones. Histone modifications, DNA methylation, and non-coding RNAs are considered to be the main epigenetic factors. Non-coding RNAs (ncRNAs) refers to ribonucleic acid (RNA) molecules that do not code for a protein. They cover a huge number of RNA classes and perform a wide range of biological functions such as regulating gene expression, protecting the genome from exogenous DNA, and directing DNA synthesis. One such class of ncRNAs that has been extensively studied are long non-coding RNAs (lncRNAs). The important role of lncRNAs in the formation and maintenance of normal homeostasis of biological systems, as well as participation in many pathological processes, has been proven. The results of recent studies indicate the importance of lncRNAs in lipid and carbohydrate metabolism. Modifications of lncRNAs expression can lead to disruption of biological processes in tissues, including fat and protein, such as adipocyte proliferation and differentiation, inflammation, and insulin resistance. Further study of lncRNAs made it possible to partly determine the regulatory mechanisms underlying the formation of an imbalance in carbohydrate and fat metabolism individually and in their relationship, and the degree of interaction between different types of cells involved in this process. This review will focus on the function of lncRNAs and its relation to hepatic carbohydrate and fat metabolism and related diseases in order to elucidate the underlying mechanisms and prospects for studies with lncRNAs.

Exosomal non coding RNAs as a novel target for diabetes mellitus and its complications.

Diabetes mellitus (DM) is a first-line priority among the problems facing medical science and public health in almost all countries of the world. The main problem of DM is the high incidence of damage to the cardiovascular system, which in turn leads to diseases such as myocardial infarction, stroke, gangrene of the lower extremities, blindness and chronic renal failure. As a result, the study of the molecular genetic mechanisms of the pathogenesis of DM is of critical importance for the development of new diagnostic and therapeutic strategies. Molecular genetic aspects of the etiology and pathogenesis of diabetes mellitus are intensively studied in well-known laboratories around the world. One of the strategies in this direction is to study the role of exosomes in the pathogenesis of DM. Exosomes are microscopic extracellular vesicles with a diameter of 30-100 nm, released into the intercellular space by cells of various tissues and organs. The content of exosomes depends on the cell type and includes mRNA, non-coding RNAs, DNA, and so on. Non-coding RNAs, a group of RNAs with limited transcriptional activity, have been discovered to play a significant role in regulating gene expression through epigenetic and posttranscriptional modulation, such as silencing of messenger RNA. One of the problems of usage exosomes in DM is the identification of the cellular origin of exosomes and the standardization of protocols for molecular genetic studies in clinical laboratories. In addition, the question of the target orientation of exosomes and their targeted activity requires additional study. Solving these and other problems will make it possible to use exosomes for the diagnosis and delivery of drugs directly to target cells in DM. This study presents an analysis of literature data on the role of exosomes and ncRNAs in the development and progression of DM, as well as the prospects for the use of exosomes in clinical practice in this disease.

The role of noncoding RNAs in the osteogenic differentiation of human periodontal ligament-derived cells.

Human periodontal ligament-derived cells are important seed cells for periodontal regeneration, and their osteogenic potential closely affects alveolar bone repair and periodontal regeneration. Human periodontal ligament stem cells are pluripotent stem cells of mesenchymal origin, which can differentiate in osteoblasts and cementoblasts. However, the molecular mechanism of this differentiation activity is poorly studied. Noncoding RNAs (ncRNAs) belong to RNAs, which do not encode proteins and represent a large segment of the human transcriptome, mainly including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). It was shown that ncRNAs is involved in the proliferation and differentiation of cells, epigenetic modifications, apoptosis, as well as in complex control and pathogenesis of various diseases. NcRNAs are actively involved in the regulation of osteogenic genes in human periodontal ligament-derived cells. This article reviews the research progress of ncRNAs in the regulatory targets, pathways and functions of ncRNAs in the osteogenic differentiation of human periodontal ligament-derived cells.

The role of circular RNAs in the pathophysiology of oral squamous cell carcinoma.

Circular RNAs are non-coding RNAs that widely exist in eukaryotes. The research progress of its generation mechanism and biological function show that circular RNAs may be used in the development of tumors, neurological diseases, cardiovascular diseases. They play an important role in the occurrence and development of diseases and has a potential to be used as a disease marker. Oral squamous cell carcinoma is one of the most common malignant tumors in oral surgery. It is difficult to treat, easy to metastasize, and has a poor prognosis. Due to its unclear mechanism, blocking oral squamous cell carcinoma at the genetic level cannot be achieved. The research progress of circular RNA in the field of oral squamous cell carcinoma will bring new ideas for the biological treatment of oral squamous cell carcinoma. This review summarizes the circRNAs mechanism, the biological function and the research progress in the development of tumors, especially oral squamous cell carcinoma.

Role of miRNAs in vascular development.

The development of the vertebrate vascular system is an extremely important and complex process. The circulatory system is the first organ system to develop during embryogenesis. The development of the vasculature into highly branched canals must occur clearly in many places in order to supply oxygen and nutrients to the rapidly developing embryo. This process is mediated by a coordinated response of vascular endothelial and parietal cells to heterogeneous angiogenic signals provided by tissues and organs. MicroRNAs regulate gene expression at the transcriptional and post-transcriptional levels and participate in many important physiological and pathological processes. MicroRNAs mainly play an important role in the developmental regulation of vascular smooth muscle cells and vascular endothelial cells. This article summarizes the research progress of microRNAs in vascular development in recent years, focusing on the regulatory mechanism of miR-126 and miR-17/92 families in vascular endothelial cells, as well as the miR-143/145 family, miR-21 in vascular smooth muscle cell's regulation. The research prospects of the role of microRNAs in vascular development are also presented in this article.

The role of long non-coding RNA ANRIL in the development of atherosclerosis.

Atherosclerosis is an important pathological basis of coronary heart disease, and the antisense non-coding RNA in the INK4 locus (ANRIL) is located in the genetically susceptible segment with the strongest correlation with it - the short arm 2 region 1 of chromosome 9 (Chr9p21). ANRIL can produce linear, circular and other transcripts through different transcriptional splicing methods, which can regulate the proliferation and apoptosis of related cells and closely related to the development of atherosclerotic plaques. Linear ANRIL can regulate proliferation of vascular smooth muscle cells (VSMCs) in plaques by chromatin modification, as well as affecting on proliferation and the apoptosis of macrophages at the transcriptional level; circular ANRIL can affect on proliferation and apoptosis of VSMCs by chromatin modification as well as interfering with rRNA maturation. In this review we describe the evolutionary characteristics of ANRIL, the formation and structure of transcripts, and the mechanism by which each transcript regulates the proliferation and apoptosis of vascular cells and then participates in atherosclerosis.