Ribonucleic Acid Research Articles

Expression profile of messenger and micro RNAs related to the histaminergic system in patients with five subtypes of breast cancer.

Disparities in estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67 proliferation indices facilitate the categorization of breast cancer into four principal subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). Preclinical studies investigating the therapeutic potential of histaminergic system targeting in breast cancer have shown promising results. This study aimed to assess the expression profiles of messenger ribonucleic acid (mRNA) and micro RNA (miRNA) related to the histaminergic system in five subtypes of breast cancer among Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B (n = 196, including HER2-, n =100; HER2+, n= 96), HER2+ (n = 36), and TNBC (n = 43). They underwent surgery during which the tumor tissue was removed along with a margin of healthy tissue (control material). Molecular analysis included the determination of a microarray profile of mRNAs and miRNAs associated with the histaminergic system, real-time polymerase chain reaction preceded by reverse transcription of selected genes, and determination of histamine receptors (human histamine H1 receptor [HRH1], human histamine H2 receptor [HRH2], and human histamine H4 receptor [HRH4]) using an enzyme-linked immunosorbent assay. Statistical analysis was performed with statistical significance at p < 0.05. Nine mRNAs were significantly differentiated in breast cancer sections, regardless of subtype, compared to control samples: HRH1, HRH2, HRH4, histamine N-methyltransferase (HNMT), 5-hydroxytryptamine receptor 6 (HTR6), endothelin 1 (EDN1), endothelin receptor type A (EDNRA), adenosine deaminase (ADA), solute carrier family 22 member 3 (SLC3A2). Predictive analysis showed that hsa-miR-34a potentially regulates HRH1 expression, whereas hsa-miR-3140-5p and hsa-miR-4251 potentially affect HRH2 expression. In contrast, HRH4 and EDN1 expression were regulated by hsa-miR-1-3p. The expression of HNMT is potentially regulated by one miRNA, hsa-miR-382, whereas EDNRA expression is regulated by two miRNA molecules: hsa-miR-34a and hsa-miR-16. In contrast, hsa-miR-650 is involved in the regulation of HTR6 expression, whereas hsa-miR-1275 potentially interacts with three mRNAs: ADA, SLC23A2, and HRH1. Molecular analysis confirmed that the selected mRNA and miRNA transcripts could be promising molecular markers and therapeutic targets.

Effects of short-term, high-dose cocoa-derived flavanol supplementation on gut microbiota composition: secondary findings from a randomized, double-blind, placebo-controlled crossover study

Abstract Cocoa-derived flavanols (CDF) may act as prebiotics. However, evidence is inconsistent, and the duration and dose of CDF intake needed to elicit any prebiotic effect are undefined. This randomized, double-blind, crossover study determined the effects of short-term, high-dose dietary supplementation with CDF versus matched placebo on gut microbiota composition in 8 healthy adults. A single faecal sample was collected 8 d after supplementation with 900 mg/d CDF or placebo. Gut microbiota composition and Bifidobacterium spp. and Lactobacillus spp. abundance were measured as secondary outcomes by 16S ribosomal ribonucleic acid (rRNA) amplicon sequencing and quantitative polymerase chain reaction, respectively. No between-treatment differences in the relative or absolute abundance of Bifidobacterium spp. (Cohen’s d = 0.89, P = 0.22) or Lactobacillus spp. (Cohen’s d = 0.42, P = 0.65) were detected. Shannon diversity (Cohen’s d = 0.38, P = 0.04) and overall community richness (Cohen’s d = 0.34, P = 0.06) were lower following CDF supplementation versus placebo, but no between-treatment differences in β-diversity or taxa relative abundances were observed. Findings are not consistent with a clear prebiotic effect of this short-term, high-dose CDF supplementation strategy relative to placebo.

Network pharmacology mechanisms and experimental verification of licorice in the treatment of ulcerative colitis

Ethnopharmacological relevanceLicorice is widely used in the treatment of ulcerative colitis (UC) and has good antioxidant and anti-inflammatory effects, but its specific active ingredients and mechanisms of action are still unknown. The purpose of the studyTo elucidate the specific molecular mechanisms of licorice in the treatment of UC and to experimentally verify its activity. MethodsThrough network pharmacology, the active ingredients of licorice and the molecular targets of UC were identified. A traditional Chinese medicine (TCM)-components-target-disease network diagram was established, and the binding energies of the active ingredient and targets of licorice were verified by molecular docking. A BALB/c mice model of UC was established by treatment with 3% dextran sulfate sodium (DSS). The effect of licorice on colon tissue injury was histologically assessed. The expression of IL-6 and IL-17 in colon tissue was detected by immunohistochemistry (IHC). Transmission electron microscopy (TEM) was used to observe morphological changes in mitochondria in the colon. Caco2 cells were treated with lipopolysaccharide (LPS) for 24 h to establish the cell inflammatory damage model, and cells were exposed to different concentrations of drug-containing serum of Licorice (DCSL) for 24 h. In cells treated with the drug, the contents of oxidation markers were measured and ELISA was used to determine the levels of inflammatory factors in the cells. TEM was used to observe morphological changes in mitochondria. ZO-1 and occludin were detected by Western blotting. DCSL effects on autophagy were evaluated by treating cells with DCSL and autophagy inhibitor for 24 h after LPS injection. Small interfering ribonucleic acid (si-RNA) was used to silence Nrf2 gene expression in Caco2 cells to observe the effects of DCSL on autophagy through the Nrf2/PINK1 pathway. Nrf2, PINK1, HO-1, Parkin, P62, and LC3 were detected by Western blotting. ResultsNinety-one active ingredients and 339 action targets and 792 UC disease targets were identified, 99 of which were overlapping targets. Molecular docking was used to analyze the binding energies of liquiritin, liquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid to the targets, with glycyrrhetinic acid having the strongest binding energy. In the UC mouse model, licorice improved colon histopathological changes, reduced levels of IL-6 and IL-17 and repaired mitochondrial damage. In the LPS-induced inflammation model of Caco2 cells, DCSL decreased MDA, IL-1β, Il-6, and TNF-α levels and increased those of Superoxide Dismutase (SOD), glutathione peroxidase (GSH-PX), and IL-10, and improved the morphological changes of mitochondria. Increased expression of Nrf2, PINK1, Parkin, HO-1, ZO-1, occludin, P62, and LC3 promoted autophagy and reduced inflammation levels. ConclusionLicorice improves UC, which may be related to the activation of the Nrf2/PINK1 signaling pathway that regulates autophagy.

Meningoencephalitis with malacia caused by Sarcocystis calchasi in a rock pigeon in Japan.

Sarcocystis spp. cause pigeon protozoan encephalitis, a neuronal disease. A female pigeon exhibiting torticollis had a necrotic area in the cerebral hemisphere surrounded by lesions with perivascular cuffing, gliosis, granulomatous foci, and meningitis. Non-necrotic lesions were also observed in the brainstem. Intact and degenerative schizonts were observed within the neuropils and neurons in the lesions. Deoxyribonucleic acid (DNA) was extracted from paraffin-embedded brain tissues and genetically analyzed after gel electrophoresis to determine Sarcocystis spp. using specific primer sets for 28S ribosomal ribonucleic acid and internal transcribed spacer region-1. DNA sequencing confirmed a significant homology with S. calchasi. This is the first report of meningoencephalitis with malacia caused by S. calchasi in a rock pigeon in Japan.

Targeted regulation of miR-154-5p/Cullin2 pathway by hsa_circ_TRIM22 in promoting human papillomavirus 16 positive cervical cancer progression.

Background. Tripartite motif-containing 22 (TRIM22) is characterized by a canonical RING domain with ubiquitin E3 ligase activity and is closely associated with tumorigenesis. As a product of TRIM22 transcription, whether hsa_circ_TRIM22 has a function of regulating tumorigenesis is unclear. Thus, we aimed to explore the role and mechanism of hsa_circ_TRIM22 in human papillomavirus (HPV) 16 positive cervical cancer (CC). Methods. We collected HPV16-positive cervical tissues including chronic cervicitis, high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), and CC, and along with CC cell lines to detect the hsa_circ_TRIM22 level using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Hsa_circ_TRIM22 was silenced using specific short hairpin ribonucleic acid (shRNA) in CC cell lines and functional assays were performed thereafter. Mechanistically, the targeting and regulatory relationship between hsa_circ_TRIM22 and miR-154-5p were confirmed using the luciferase report assay and rescue experiments. Results. We found hsa_circ_TRIM22 expression level was significantly higher in CC cells and tissues. Further, hsa_circ_TRIM22 knockdown inhibited migration, proliferation, invasiveness, enhanced apoptosis, and slowed the cell cycle. Mechanistically, hsa_circ_TRIM22 could bind miR-154-5p and prevent miR-154-5p from reducing the levels of Cullin2 (CUL2). Notably, the application of miR-154-5p inhibitor significantly rescued hsa_circ_TRIM22-mediated tumorigenesis. Conclusions. Our observations suggest hsa_circ_TRIM22 is upregulated in HPV16-positive CC and promotes CC progression by regulating the miR-154-5p/CUL2 axis, thereby serving as a promising candidate for diagnosis and treatments of CC.

Genetic underpinnings of the sex bias in autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopment condition featuring difficulties in social interaction and communication. ASD is also well-known for its sex bias, in which males are diagnosed approximately four times more frequently than females. Although recent sequencing studies have identified a genetic etiology of ASD, the sex bias in ASD still remains largely unexplained because the frequencies of autosomal ASD-associated genetic variations are equivalent between males and females. We hypothesized that if the intrinsic expression levels of ASD-associated genes are different between males and females, they may contribute to the sex bias in ASD. Aiming to decode the genetic contribution to the ASD sex bias, we determined whether gene expression levels of ASD-associated genes were different between undiagnosed males and females. Analyses of the ribonucleic acid sequencing (RNAseq) data from the Genotype-Tissue Expression consortium (GTEx) revealed modest differences for 17 ASD-associated genes in the relevant brain regions between males and females. These candidate genes showed stronger collective sex-dependent expression in the gene set enrichment analysis, which was subsequently validated by the RNAseq data from the PsychENCODE consortium. In addition, gene ontology analysis revealed the functional relevance of the 17 candidate genes in chromatin remodeling and synaptic regulation. Taken together, these candidate genes discovered through big data analysis suggest that sex-dependent expression of ASD-associated genes may contribute to the sex bias in ASD. These novel insights into the sex bias may refine underlying disease mechanisms of ASD, potentially informing therapeutic strategies for improving the quality of life of diagnosed individuals.

Disease-associated gut microbiome and metabolome changes in rats with chronic hypoxia-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a progressive disease affecting the lung vasculature that is characterized by sustained vasoconstriction and leads to vascular remodeling. The lung microbiome contributes to PH progression, but the function of the gut microbiome and the correlation between the gut microbiome and metabolome remain unclear. We have analyzed whether chronic hypoxia-induced PH alters the rat fecal microbiota. We explored hypoxia-induced pulmonary hypertension model rats to find out the characteristic changes of intestinal microorganisms and metabolites of hypoxia-induced pulmonary hypertension, and provide a theoretical basis for clinical treatment. In the current study, a chronic hypoxia-induced PH rat model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the occurrence and development of PH. 16S ribosomal ribonucleic acid (16S rRNA), short-chain fatty acid (SCFA) measurements, mass spectrometry (MS) metabolomics analysis and metatranscriptome were performed to analyze stool samples. The datasets were analyzed individually and integrated for combined analysis using bioinformatics approaches. Our results suggest that the gut microbiome and metabolome of chronic hypoxia-induced PH rats are distinct from those of normoxic rats and may thus aid in the search for new therapeutic or diagnostic paradigms for PH. The gut microbiome and metabolome are altered as a result of chronic hypoxia-induced PH. This imbalanced bacterial ecosystem might play a pathophysiological role in PH by altering homeostasis.

Synthesis and bioactivity of a novel surfactin-based lipopeptide for mRNA delivery.

The effective delivery of messenger ribonucleic acid (mRNA) to specific cell types and target tissues poses a significant challenge in nonviral therapeutic strategies. Lipid-based nanoparticles (LNPs) have emerged as a leading carrier system for delivering mRNA, particularly for infectious diseases, such as COVID-19. This study aimed to describe the synthesis of a novel lipopeptide based on surfactin, a naturally occurring surfactant. Additionally, a series of novel LNPs were rationally designed, based on the modified surfactin, OleSurf, and were formulated and optimized. The physicochemical properties, morphologies, and stabilities of the particles were evaluated. All formulations containing OleSurf produced particles with a diameter <80 nm and an encapsulation efficiency >95%. OleSurf LNPs demonstrated excellent transfection efficiency and luciferase expression with no cytotoxicity, compared to lipofectamine 2000, a known transfection reagent, and were comparable to the DLin-MC3-DMA lipid. OleSurf-based LNPs behaved as efficient mRNA carriers and showed enhanced mRNA-binding capabilities, associated with facilitated intracellular release, endosomal escape, and protection from endonuclease degradation. In addition, OleSurf-LNPs showed a higher mRNA delivery efficiency, a more advantageous biodistribution pattern, and an improved safety profile in vivo. Overall, the novel OleSurf LNPs presented an optimal delivery platform for mRNA therapeutics.

Состояние микробиома десневой борозды детей с бронхиальной астмой

Aim. To compare the microbiome of the healthy gingival sulcus of children with bronchial asthma (BA) and different dental conditions. Design. Open comparative clinical and laboratory study. Materials and methods. Gingival substrate was obtained from 19 children aged 3–6 years with exacerbation of BA; the results of sequencing the genes of 16 subunits of ribosomal ribonucleic acid (16S rRNA) on the MiSeq platform (Illumina) were analyzed. Results. Five major phyla have been identified in the gingival sulcus: Firmicutes, Proteobacteria, Actinobacteria, Fusobacterium and Bacteroidetes and the dominant genus, Streptococcus. A significantly high relative prevalence of the species Neisseria oralis (p = 0.0073), Hemophilic massiliensis (p = 0.046), Hemophilic paraphrohaemolyticus (p = 0.05) and Lautropia mirabilis (p = 0.05) in children with asthma without caries was established. The level of immunoglobulin E (IgE) is significantly higher in children with asthma and caries compared to children without caries (461.79 ± 60.58 and 276.97 ± 81.15 IU/ml). Conclusion. The predominance of opportunistic and “healthy” bacterial species of the phylum Proteobacteria in the healthy gingival sulcus of children with BA may be an indicator of oral dysbiosis in BA. Overproduction of IgE in children with caries may be due to cariogenic flora, which requires further study. Keywords: sequencing, gingival crevicular microbiome, children, bronchial asthma, caries.

Analysis of Phage Regulatory RNAs: Sequencing Library Construction from the Fraction of Small Prokaryotic RNAs Less Than 50 Nucleotides in Length.

So far, bacterial regulatory sRNAs of length less than 50 nucleotides have been poorly understood, and a low number of such molecules has been identified. The first microRNA-size functional ribonucleic acid occurring in a bacterial cell has been described only recently, and it was found to be encoded by a bacteriophage. One of the reasons for such a scarcity in this field is the lack of procedures intended for the isolation and selection of molecules of this size from bacterial cells. To meet these difficulties, we describe here the few-step procedure of isolation, purification, selection, and sequencing library preparation that is dedicated to the fraction of very small, bacterial RNA molecules.

Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction.

The adiponectin (APN) levels in obesity are negatively correlated with chronic subclinical inflammation markers. The hypertrophic adipocytes cause obesity-linked insulin resistance and metabolic syndrome. Furthermore, macrophage polarization is a key determinant regulating adiponectin receptor (AdipoR1/R2) expression and differential adiponectin-mediated macrophage inflammatory responses in obese individuals. In addition to decrease in adiponectin concentrations, the decline in AdipoR1/R2 messenger ribonucleic acid (mRNA) expression leads to a decrement in adiponectin binding to cell membrane, and this turns into attenuation in the adiponectin effects. This is defined as APN resistance, and it is linked with insulin resistance in high-fat diet-fed subjects. The insulin-resistant group has a significantly higher leptin-to-APN ratio. The leptin-to-APN ratio is more than twofold higher in obese individuals. An increase in expression of AdipoRs restores insulin sensitivity and β-oxidation of fatty acids via triggering intracellular signal cascades. The ratio of high molecular weight to total APN is defined as the APN sensitivity index (ASI). This index is correlated to insulin sensitivity. Homeostasis model of assessment (HOMA)-APN and HOMA-estimated insulin resistance (HOMA-IR) are the most suitable methods to estimate the metabolic risk in metabolic syndrome. While morbidly obese patients display a significantly higher plasma leptin and soluble (s)E-selectin concentrations, leptin-to-APN ratio, there is a significant negative correlation between leptin-to-APN ratio and sP-selectin in obese patients. When comparing the metabolic dysregulated obese group with the metabolically healthy obese group, postprandial triglyceride clearance, insulin resistance, and leptin resistance are significantly delayed following the oral fat tolerance test in the first group. A neuropeptide, Spexin (SPX), is positively correlated with the quantitative insulin sensitivity check index (QUICKI) and APN. APN resistance together with insulin resistance forms a vicious cycle. Despite normal or high APN levels, an impaired post-receptor signaling due to adaptor protein-containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1)/APPL2 may alter APN efficiency and activity. However, APPL2 blocks adiponectin signaling through AdipoR1 and AdipoR2 because of the competitive inhibition of APPL1. APPL1, the intracellular binding partner of AdipoRs, is also an important mediator of adiponectin-dependent insulin sensitization. The elevated adiponectin levels with adiponectin resistance are compensatory responses in the condition of an unusual discordance between insulin resistance and APN unresponsiveness. Hypothalamic recombinant adeno-associated virus (rAAV)-leptin (Lep) gene therapy reduces serum APN levels, and it is a more efficient strategy for long-term weight maintenance.

EvolSOM: An R package for analyzing conservation and displacement of biological variables with self-organizing maps.

Unraveling the connection between genes and traits is crucial for solving many biological puzzles. Ribonucleic acid molecules and proteins, derived from these genetic instructions, play crucial roles in shaping cell structures, influencing reactions, and guiding behavior. This fundamental biological principle links genetic makeup to observable traits, but integrating and extracting meaningful relationships from this complex, multimodal data present a significant challenge. We introduce evolSOM, a novel R package that allows exploring and visualizing the conservation or displacement of biological variables, easing the integration of phenotypic and genotypic attributes. It enables the projection of multi-dimensional expression profiles onto interpretable two-dimensional grids, aiding in the identification of conserved or displaced genes/phenotypes across multiple conditions. Variables displaced together suggest membership to the same regulatory network, where the nature of the displacement may hold biological significance. The conservation or displacement of variables is automatically calculated and graphically presented by evolSOM. Its user-friendly interface and visualization capabilities enhance the accessibility of complex network analyses. The package is open-source under the GPL ( 3) and is available at https://github.com/sanprochetto/evolSOM, along with a step-by-step vignette and a full example dataset that can be accessed at https://github.com/sanprochetto/evolSOM/tree/main/inst/extdata.

CXCR2/Snail-1-Induced Epithelial-Mesenchymal Transition in the Formation and Progression of RCC with Inferior Vena Cava Tumour Thrombus.

Renal cell carcinoma (RCC), a common and highly invasive malignant tumour, presents clinical challenges due to its propensity for easy metastasis. Inferior vena cava tumour thrombus is a common RCC complication significantly impacting patient prognosis. This study investigates C-X-C chemokine receptor type 2 (CXCR2)/Snail-1-induced epithelial-mesenchymal transition (EMT) in RCC with inferior vena cava tumour thrombus. Tissues from 51 RCC patients were analysed for CXCR2 and Snail-1 Messenger Ribonucleic Acid (mRNA) levels using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Elevated levels of both were observed in tumour and inferior vena cava tumour thrombus tissues. Using Short Hairpin RNA (shRNA) technology, we inhibited CXCR2 and Snail-1 expression to investigate their impact on EMT, invasiveness, and metastatic potential in RCC cells. Compared with that in the Short Hairpin RNA-Negative Control (ShNC) group, inhibition of CXCR2 and Snail-1 suppressed the degree of EMT, invasiveness, and metastatic ability of RCC cells (p < 0.01). Further mechanistic studies showed that CXCR2/Snail-1 participated in the formation and progression of RCC by regulating the extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathways. Additionally, compared with that in the ShNC group, knockdown of CXCR2 and Snail-1 significantly inhibited the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9; p < 0.01), thereby regulating the metastasis of RCC. Our findings suggest that CXCR2/Snail-1-induced EMT plays an important role in the formation and progression of RCC with inferior vena cava tumour thrombus. CXCR2/Snail-1 participates in the invasion and metastasis of RCC by regulating the expression of multiple signalling pathways and related genes. These results provide new insights and directions for the treatment of RCC.

The influence of sex hormones on renal cell carcinoma.

Kidney cancer is a common malignancy that constitutes around 5% of all cancer cases. Males are twice as likely to acquire renal cell carcinoma (RCC) compared to females and experience a higher rate of mortality. These disparities indicate that sex hormone (SH)-dependent pathways may have an impact on the aetiology and pathophysiology of RCC. Examination of SH involvement in conventional signalling pathways, as well as genetics and genomics, especially the involvement of ribonucleic acid, reveal further insights into sex-related differences. An understanding of SHs and their influence on kidney cancer is essential to offer patients individualized medicine that would better meet their needs in terms of prevention, diagnosis and treatment. This review presents the understanding of sex-related differences in the clinical manifestation of kidney cancer patients and the underlying biological processes.

Obesity-Senescence-Breast Cancer: Clinical Presentation of a Common Unfortunate Cycle.

There are few convincing studies establishing the relationship between endogenous factors that cause obesity, cellular aging, and telomere shortening. Without a functional telomerase, a cell undergoing cell division has progressive telomere shortening. While obesity influences health and longevity as well as telomere dynamics, cellular senescence is one of the major drivers of the aging process and of age-related disorders. Oxidative stress induces telomere shortening, while decreasing telomerase activity. When progressive shortening of telomere length reaches a critical point, it triggers cell cycle arrest leading to senescence or apoptotic cell death. Telomerase activity cannot be detected in normal breast tissue. By contrast, maintenance of telomere length as a function of human telomerase is crucial for the survival of breast cancer cells and invasion. Approximately three-quarters of breast cancers in the general population are hormone-dependent and overexpression of estrogen receptors is crucial for their continued growth. In obesity, increasing leptin levels enhance aromatase messenger ribonucleic acid (mRNA) expression, aromatase content, and its enzymatic activity on breast cancer cells, simultaneously activating telomerase in a dose-dependent manner. Meanwhile, applied anti-estrogen therapy increases serum leptin levels and thus enhances leptin resistance in obese postmenopausal breast cancer patients. Many studies revealed that shorter telomeres of postmenopausal breast cancer have higher local recurrence rates and higher tumor grade. In this review, interlinked molecular mechanisms are looked over between the telomere length, lipotoxicity/glycolipotoxicity, and cellular senescence in the context of estrogen receptor alpha-positive (ERα+) postmenopausal breast cancers in obese women. Furthermore, the effect of the potential drugs, which are used for direct inhibition of telomerase and the inhibition of human telomerase reverse transcriptase (hTERT) or human telomerase RNA promoters as well as approved adjuvant endocrine therapies, the selective estrogen receptor modulator and selective estrogen receptor down-regulators are discussed.

A Review of Bioinformatics Methods for RNA Secondary and Tertiary Structures Prediction

Initially, it was thought that Ribonucleic acid (RNA) primarily served as a carrier of information required for protein synthesis. However, recent discoveries have unveiled RNA’s pivotal involvement in gene regulatory networks and various cellular processes. The functionality of an RNA molecule is intricately linked to its structures, including secondary and tertiary (three-dimensional) structures. Consequently, comprehending the functions of RNA necessitates a thorough understanding of its diverse structural aspects. Deciphering the secondary structure or tertiary structure of RNA from its primary sequence is a complex computational challenge. Consequently, several methods and techniques have been devised to address this issue. Initially, physical techniques like X-Ray, Crystallography, and Nuclear Magnetic Resonance were employed, but they proved to be expensive, labor-intensive, and time-consuming. As a result, the demand for bioinformatics methods has significantly increased to tackle this problem more efficiently. In this paper, we will explore the various employed methods for predicting the different RNA structures, encompassing both secondary and tertiary structures.

Gene Silencing and Gene Delivery in Therapeutics: Insights Using Quantum Dots.

Hemophilia, cancer, diabetes, cardiovascular disease, mental health issues, immunological deficiencies, neuromuscular disease, blindness, and other ailments can all be treated with gene silencing and gene therapy, a growing discipline in medicine. It typically refers to a range of therapeutic techniques in which a patient's body's particular cells are given genetic material designed to correct and erase genetic flaws. The advancements in genetics and bioengineering have paved the way for the conceptualization of gene therapy through the manipulation of vectors, enabling the targeted transfer of extrachromosomal material to specific cells. One of the main focus areas of this methodology is the escalation of delivery vehicles (vectors), primarily plasmids or viruses; it still has difficulties because there is no good delivery mechanism that can precisely deliver stable small interfering Ribonucleic Acid (siRNA) or DNA to the target tissue location. As they are non-fluorescent, the siRNA or DNA delivery procedure is unable to be monitored by these carriers. In the context of quantum dots (QDs), the formation of QD-siRNA or QD/DNA complexes facilitated the real-time monitoring and precise localization of QDs during the silencing, delivery, and transfection processes. The unique dual-modality optical and fluorescent properties exhibited by quantum dots contribute to their utility as versatile imaging probes. The research studies discussed in this review article will provide a framework for designing efficient QD-based nanocarriers that can successfully carry therapeutic genetic tools into targeted cells. As a result of their findings, the researchers developed some unique QDs that successfully attached to the siRNA or DNA and carried it to the desired place. The use of these QD-based delivery devices could enhance the field of gene silencing and gene delivery.

Coordinating Poly(I:C) and Aluminum within Liposomal Vesicles for Enhanced Innate Immune Activation

PolyIC is a double-stranded RNA formed by two complementary ribonucleic acid chains: inosine and cytidine. It is a synthetic analog RNA that mimics the viral genome. PolyIC can activate downstream signal pathways to trigger interferon (IFNs) production after it is uptaken by antigen presenting cells and recognized by the Toll-like receptors (TLRs) located in the endosomal system. The productions of interferon have the functions such as enhancing antigen presentation and immune modulation, and stimulating innate immune responses. However, the delivery of PolyIC into tumors is hampered by RNases present in physiological conditions, which leads to enzymatic degradation. To address the delivery challenge, we encapsulated and stabilized the PolyIC into liposomes, which are lipid-bilayer nanoparticles that enclose and carry drugs inside the core, using the coordination of metals and phosphate on ribose. By using aluminum as the coordination metal, an adjuvant often used with vaccines to enhance immunity, we found that PolyIC synergized with coordinating aluminum to activate macrophages and increase the production of interferons. The results proved that the coordinating liposomes Al-PolyIC allowed for evasion from enzymatic degradation and enhancement of innate immune response.

Short term antibiotic effects on gut microbiome in Indian preschoolers: A 16S rRNA analysis

Objectives: Antibiotic use is associated with dysbiosis of the gut microbiome. The objective of this study is to investigate the effect of antibiotics on gut composition in children aged 3–5 years receiving antibiotics compared to children who did not receive antibiotics. Materials and Methods: A total of 54 participants aged 3–5 years were included in this multi-centric cohort study. Participants were divided into two equal groups, that is the treatment-experienced group (Group 1, n = 27, antibiotic) and the treatment-not-experienced group (Group 2, n = 27, non-antibiotic). Stool samples of study participants were collected on days 0 and 5 (± 1 day) and analyzed using 16Svedberg ribosomal ribonucleic acid (16S rRNA) gene sequencing. Statistical Analysis: The Kruskal-Wallis H-test and Benjamini-Hochberg FDR correction were applied to determine the differentially abundant pathways across the zones using Statistical Analysis of Metagenomic Profiles (STAMP) (v2.1.3). Results: A non-significant increase in the mean abundance of the Phyla Bacteroidota, Proteobacteria, Actinobacteria, and Verrucomicrobiota was observed in both groups from day 0 to day 5. An alteration in the Firmicutes/Bacteroidetes ratio was observed. A significant (P &lt; 0.05) abundance of genus Enterobacteriaceae, Enterococcaceae, and Lactobacillaceae was observed in the participants with antibiotic treatment. The relative abundance of families Enterococcus, Lactobacillus, Sellimonas, Ruminococcus, Torques, and Eggerthella groups was observed to be significantly higher (P &lt; 0.05) in participants with antibiotic treatment. Beta-diversity indices revealed significant differences at group and subgroup levels regarding the bacterial counts. Conclusions: It was observed that a short-term course of 5 days of antibiotic usage is associated with altered microbial abundance and diversity.

Effect of Exercise Training on Peroxisome Proliferator-Activated Receptor γ (PPAR-γ) Level: A Systematic Review

Context: Peroxisome proliferator-activated receptor γ (PPAR-γ) plays a crucial role in regulating oxidative phosphorylation and energy utilization, both of which are diminished in obesity and type 2 diabetes (T2DM), major risk factors for cardiovascular disease (CVD). It is well established that exercise, as one of the significant modifiable lifestyle factors, is associated with the expression and activity of PPAR-γ-controlled genes. Evidence Acquisition: In this systematic review, we conducted comprehensive searches across various databases, including PubMed, ScienceDirect, and Google Scholar, for relevant literature published between January 2000 and May 2022. This study focused on published articles (in-vivo and human) in English. This review encompasses 16 studies (4 involving humans and 12 involving animals). Results: The findings from 14 studies indicated that various types of exercise programs, including regular exercise, resistance exercise, swimming, climbing, and treadmill running, effectively improved PPAR-γ levels in individuals with T2DM, obese populations, and healthy subjects. Only two studies reported no significant improvement in PPAR-γ levels following physical activity. Notably, all studies involving subjects with T2DM showed improved PPAR-γ levels after exercise training. Conclusions: Upon comparing various types of exercise training, the collected data suggest that all forms of aerobic exercise, regardless of their type and duration, have the potential to up-regulate PPAR-γ messenger ribonucleic acid (mRNA) expression. This study lays the foundation for further research into the association between different types of exercise training and PPAR-γ levels/activity across various human populations. However, given the limited number of human studies, further high-quality research is necessary to draw firm conclusions.