Coevolution of ribosomal RNA expansion segment 7L and assembly factor Noc2p specializes the ribosome biogenesis pathway between Saccharomyces cerevisiae and Candida albicans.

Ribosomes of different species share an evolutionarily conserved core, exhibiting flexible shells formed partially by the addition of species-specific ribosomal RNAs (rRNAs) with largely unexplored functions. In this study, we showed that by swapping the Saccharomyces cerevisiae 25S rRNA genes with non-S. cerevisiae homologs, species-specific rRNA variations caused moderate to severe pre-rRNA processing defects. Specifically, rRNA substitution by the Candida albicans caused severe growth defects and deficient pre-rRNA processing. We observed that such defects could be attributed primarily to variations in expansion segment 7L (ES7L) and could be restored by an assembly factor Noc2p mutant (Noc2p-K384R). We showed that swapping ES7L attenuated the incorporation of Noc2p and other proteins (Erb1p, Rrp1p, Rpl6p and Rpl7p) into pre-ribosomes, and this effect could be compensated for by Noc2p-K384R. Furthermore, replacement of Noc2p with ortholog from C. albicans could also enhance the incorporation of Noc2p and the above proteins into pre-ribosomes and consequently restore normal growth. Taken together, our findings help to elucidate the roles played by the species-specific rRNA variations in ribosomal biogenesis and further provide evidence that coevolution of rRNA expansion segments and cognate assembly factors specialized the ribosome biogenesis pathway, providing further insights into the function and evolution of ribosome.

Long noncoding RNA HOXA-AS2 ameliorates chronic intermittent hypoxia-induced lung inflammation by regulating miR-17-5p/tipe2 axis.

PURPOSE: The purpose is to confirm whether long noncoding RNA HOXA-AS2 relieves chronic intermittent hypoxia (CIH)-induced lung inflammation. METHODS: Male Sprague Dawley rats were used to establisha CIH rat model. Hematoxylin and Eosin staining was used on the lung tissue injury to determine the successful construction of CIH animal model. Arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) were measured. HOXA-AS2 was overexpressed to evaluate its role in the progression and development of CIH. T cell differentiation and cytokine production were determined using flow cytometry. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labelling assay kit. The target of HOXA-AS2 and miR-17-5p was predicted by the Encyclopedia of RNA Interactomes (ENCORI) and confirmed using luciferase assay. RESULTS: HOXA-AS2 was downregulated in CIH rat models. Lung tissue injury was observed in CIH rats, and the injury was attenuated by the overexpression of HOXA-AS2. PaO2 was reduced and PaCO2 was induced in CIH rats, which was reversed by the overexpression of HOXA-AS2. The overexpression of HOXA-AS2 inhibited CIH-induced cell apoptosis. It also reversed alterations in the levels of interferon gamma (IFNγ), interleukin (IL)-2, IL-6, IL-1ß, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-ß1) in rats caused by CIH. The overexpression of HOXA-AS2 prevented the induction in CD4+ IFN-γ+ T cells and reduction in CD4+TGF-ß1+ T cells. The overexpression of HOXA-AS2 upregulated tumor necrosis factor-alpha-induced protein 8-like 2 (tipe2) key regulator through directly targeting miR-17-5p. Further experiments proved that tipe2 was the direct target of miR-17-5p. CONCLUSION: This study manifested that HOXA-AS2 acted as an anti-inflammatory regulator and protected lung tissue injury from CIH in the rat model; this was mediated by upregulation of tipe2 through directly targeting miR-17-5p. HOXA-AS2 upregulated the expression of tipe2, providing new understanding and therapeutic target for CIH.

Continuous positive airway pressure effectively ameliorates arrhythmias in patients with obstructive sleep apnea-hypopnea via counteracting the inflammation.

INTRODUCTION: This work is aimed at evaluating the therapeutic effect of continuous positive airway pressure (CPAP) in treatment of patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) combined with arrhythmias as well as clarifying the possible mechanism underpinning such an intervention. METHODS: Through exclusions, a total of 108 OSAHS patients combined with arrhythmias were enrolled from June 2017 to June 2019 with full clinical information in this work. A computerized permuted block design with varying block stratification and size according to age, sex, AHI and type of arrhythmia was used to randomize 108 patients to CPAP versus sham CPAP for a period of 12-week. All were subjected to unchanged pharmacological anti-arrhythmia therapy combined with CPAP. Before and after CPAP treatment, the improvement of various arrhythmias was compared between the CPAP group and the sham-CPAP group. The levels of CRP, IL-6 and TNF-ɑ were measured simultaneously. RESULTS: During follow-up, the mean (±SD) CPAP pressure used in the CPAP group was 12.3 (±3.1) cm H2O. The use of CPAP and sham CPAP was on average of 5.2 ± 0.56 and 5.1 ± 0.63 h/night, respectively. After 12 weeks of CPAP therapy, the AHI was significantly decreased and the lowest blood oxygen saturation was notably elevated in the CPAP group compared to the sham-CPAP group, P < 0.05. The CPAP therapy, compared with the sham-CPAP group, significantly reduced the incidence of all types of arrhythmia in patients with OSAHS. The level of the c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) was significantly lower in the CPAP group than in the sham-CPAP group (P < 0.05). Pearson correlation analysis showed that the reduction in the incidence of total arrhythmias was positively correlated with the decrease of CRP, IL-6 and TNF-ɑ levels, respectively. CONCLUSION: Findings from this work suggest that proper use of CPAP significantly benefits to OSAHS patients combined with arrhythmias, possibly via counteracting the inflammation.

The ethylene response factor SmERF6 co-regulates the transcription of SmCPS1 and SmKSL1 and is involved in tanshinone biosynthesis in Salvia miltiorrhiza hairy roots.

MAIN CONCLUSION: The SmERF6, which recognizes the GCC-box of SmCPS1 and SmKSL1 promoter in nucleus, regulates the tanshinone biosynthesis in Salvia miltiorrhiza hairy roots. Tanshinone, an important medicinal ingredient in Salvia miltiorrhiza, is best known for its use in medicine. However, the transcription factor regulation of tanshinone biosynthesis is unclear. Here, we isolated and identified a transcription factor in the ERF family of S. miltiorrhiza, SmERF6, which was screened from an S. miltiorrhiza cDNA library by the promoters of two key tanshinone synthesis genes (SmKSL1 and SmCPS1); this factor regulated tanshinone biosynthesis. The gene was highly expressed in the root and responded to ethylene treatment. SmERF6 modulated tanshinone biosynthesis by directly binding to an ethylene-responsive element (GCC-box) of the SmKSL1 and SmCPS1 promoters and activating their transcription. Overexpression of SmERF6 in the hairy roots increased their tanshinone accumulation, and SmERF6 silencing by RNAi led to a lower tanshinone content. Furthermore, tanshinone accumulation maintained homeostasis with the total phenolic acid and flavonoid contents in S. miltiorrhiza. These findings elucidated how SmERF6 directly co-regulates the transcription of SmCPS1 and SmKSL1 and modulates tanshinone synthesis to accelerate the metabolic flux of tanshinone accumulation in S. miltiorrhiza.

Genome-wide association study identifies the genetic basis of key agronomic traits in 207 sugar beet accessions.

Sugar beet (Beta vulgaris) has emerged as one of the two primary crops, alongside sugarcane, for global sugar production. Comprehensively understanding sucrose synthesis, transport, and accumulation in sugar beet holds great significance for enhancing sugar production. In this study, we collected a diverse set of 269 sugar beet accessions worldwide and measured 12 phenotypes, comprising biomass, soluble sugar content, and 10 taproot-related traits. We re-sequenced 207 accessions to explore genetic diversity and population structure. Then we employed a genome-wide association study (GWAS) and RNA-seq to identify single-nucleotide polymorphisms and genes associated with natural phenotypic variations. Our findings revealed a panel of genes potentially regulating biomass and sugar accumulation, notably the dual-role gene UDP-glucose 4-epimerase, which genetically balances sugar accumulation and cell wall synthesis. In summary, this study provides a foundation for molecular breeding in sugar beet.

Glyceollins from soybean: Their pharmacological effects and biosynthetic pathways.

Flavonoids are a highly abundant class of secondary metabolites present in plants. Isoflavonoids, in particular, are primarily synthesized in leguminous plants within the subfamily Papilionoideae. Numerous reports have established the favorable role of isoflavonoids in preventing a range of human diseases. Among the isoflavonoid components, glyceollins are synthesized specifically in soybean plants and have displayed promising effects in mitigating the occurrence and progression of breast and ovarian cancers as well as other diseases. Consequently, glyceollins have become a sought-after natural component for promoting women's health. In recent years, extensive research has focused on investigating the molecular mechanism underlying the preventative properties of glyceollins against various diseases. Substantial progress has also been made toward elucidating the biosynthetic pathway of glyceollins and exploring potential regulatory factors. Herein, we provide a review of the research conducted on glyceollins since their discovery five decades ago (1972-2023). We summarize their pharmacological effects, biosynthetic pathways, and advancements in chemical synthesis to enhance our understanding of the molecular mechanisms of their function and the genes involved in their biosynthetic pathway. Such knowledge may facilitate improved glyceollin synthesis and the creation of health products based on glyceollins.

Delayed senescence of apple leaves by exogenous melatonin treatment: toward regulating the ascorbate-glutathione cycle.

The objectives of this study were to test the effects of exogenous melatonin on apple (Malus domestica Borkh. cv. Golden Delicious) leaves and investigate its possible physiological role in delaying leaf senescence. Detached leaves treated with 10 mm melatonin solutions clearly showed a slowing in their process of dark-induced senescence, as evidenced by both biochemical and molecular parameters. Melatonin delayed the normal reduction in chlorophyll content and maximum potential photosystem II efficiency (F(v) /F(m) ). It also suppressed the transcript levels of a key chlorophyll degradation gene, pheide a oxygenase (PAO), and the senescence-associated gene 12 (SAG12). This outcome was thought to be because of the enhanced antioxidant capabilities of melatonin. Indeed, H(2) O(2) accumulation was inhibited by exogenous melatonin, which might have resulted from direct reactive oxygen species scavenging by melatonin and a great enhancement of ascorbate peroxidase (APX; EC 1.11.1.11), which acted on both mRNA and protein activity levels. Melatonin treatment led to the maintenance of higher contents of ascorbic acid (AsA) and glutathione (GSH) but less dehydroascorbate (DHA) and oxidized glutathione (GSSG) compared with the control, possibly through its regulation of the AsA-GSH cycle.

The complete chloroplast genomes of Lycopus lucidus and Agastache rugosa, two herbal species in tribe Mentheae of Lamiaceae family.

Lamiaceae is one of the largest families in the kingdom Plantae, including lots of traditional Chinese herbs. Lycopus lucidus and Agastache rugosa are two Lamiaceae species, which are most frequently used in Chinese traditional medicine. In the current study, the complete chloroplast genome sequences of two species were assembled. Their circular DNA lengths were 152,096 and 151,922 bp respectively. Both genomes were made up of a large single-copy region, a small single-copy region, and a pair of inverted repeat regions. Each genome totally encoded 133 genes, containing 88 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicated that both species belong to the Mentheae tribe of the Lamiaceae family.

The complete chloroplast genome of Isodon rubescens, a traditional Chinese herb.

Isodon rubescens (Hemsley) H. Hara is a kind of traditional medical herb which can be used for cancer treatment. In this study, the complete chloroplast genome sequence of I. rubescens was assembled. Its complete circular chloroplast DNA length was 152,761 bp. The genome was made up of a large single-copy region of 83,655 bp, a small single-copy region of 17,660 bp, and a pair of inverted repeat regions of 25,723 bp. The genome totally encoded 129 genes, containing 85 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicated that I. rubescens had a close relationship with basil (Ocimum basilicum).

Network pharmacology reveals the potential mechanism of Baiying Qinghou decoction in treating laryngeal squamous cell carcinoma.

CONTEXT: Baiying Qinghou as a traditional Chinese medicine decoction shows anticancer property on laryngeal squamous cell carcinoma. However, little is known about the precise mechanism of Baiying Qinghou detection against laryngeal squamous cell carcinoma. OBJECTIVE: This study was aimed to explore potential mechanism of therapeutic actions of Baiying Qinghou decoction on laryngeal squamous cell carcinoma. MATERIALS AND METHODS: The active chemical components of Baiying Qinghou decoction were predicted, followed by integrated analysis of network pharmacology and molecular docking approach. The network pharmacology approach included target protein prediction, protein-protein interaction network construction and functional enrichment analysis. RESULTS: Sitosterol and quercetin were predicted to be the overlapped active ingredients among three Chinese herbs of Baiying Qinghou decoction. The target proteins were closely associated with response to chemical, response to drug related biological process and cancer related pathways such as PI3K-Akt signaling, HIF-1 signaling and Estrogen signaling pathway. The target proteins of TP53, EGFR, PTGS2, NOS3 and IL1B as the key nodes in PPI network were cross-validated, among which EGFR, IL1B, NOS3 and TP53 were significantly correlated with the prognosis of patients with laryngeal squamous cell carcinoma. Finally, the binding modes of EGFR, IL1B, NOS3 and TP53 with quercetin were visualized. DISCUSSION AND CONCLUSION: Quercetin of Baiying Qinghou decoction showed therapeutic effect against laryngeal squamous cell carcinoma by regulating TP53, EGFR, NOS3 and IL1B involved with drug resistance and PI3K-AKT signaling pathway. TP53, EGFR, NOS3 and IL1B may be the candidate targets for the treatment of laryngeal squamous cell carcinoma.

The complete chloroplast genome of Schizonepeta tenuifolia (Benth.) Briq., a traditional Chinese herb.

Schizonepeta tenuifolia (Benth.) Briq. is a traditional Chinese medicinal herb. The complete chloroplast genome sequence of S. tenuifolia was obtained by high-throughput sequencing platform. The chloroplast genome of S. tenuifolia is a circular form of 151,254 bp in length, with an average GC content of 37.85%. The genome contains a set of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on complete chloroplast genome sequences indicates that S. tenuifolia has a close relationship with Dracocephalum palmatum. This study provides a molecular basis for the classification of S. tenuifolia.

Characterization of the complete chloroplast genome of Clerodendrum bungei Steud. (Lamiaceae).

Clerodendrum bungei Steud. is one kind of traditional medical herb which can be used for airway hyperreactivity treatment. In this study, the complete chloroplast genome sequence of C. bungei was assembled. Its complete circular chloroplast DNA length was 151,680 bp. The genome was made up of a large single-copy region of 83,189 bp, a small single-copy region of 17,311 bp, and a pair of inverted repeat regions of 25,590 bp. The genome totally encoded 130 genes, containing 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic analysis indicates that C. bungei belongs to the Lamiaceae family.

The complete chloroplast genome of Verbena officinalis, an herbal species of Verbenaceae family.

Verbena officinalis is one kind of traditional medical herb which has potential for multiple diseases' treatment. In this study, the complete chloroplast genome sequence of V. officinalis was assembled. Its complete circular chloroplast DNA length was 153,491 bp. The genome was made up of a large single-copy region of 84,518 bp, a small single-copy region of 17,357 bp, and a pair of inverted repeat regions of 25,808 bp. The genome totally encoded 128 genes, containing 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicates that V. officinalis belongs to the verbenaceae family.

Downregulation of miR-204 facilitates the progression of nasopharyngeal carcinoma by targeting CXCR4 through NF-κB signaling pathway.

PURPOSE: Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer. The alterations of miRNA deregulation and pathway have been reported to be implicated in NPC progression. Here, we aimed to explore miR-204 role and mechanism in NPC development. METHODS: We examined the expression level of miR-204 in NPC tissues and NPC cells (HONE-1, 6-10B, HNE1) using reverse-transcription quantitative PCR (RT-qPCR) analysis. MTT, and transwell assays were used to analyze the effects of miR-204 on the proliferation, invasion and migration of NPC cells. Luciferase reporter gene assays were used to confirm the target gene of miR-204 in NPC cells. RESULTS: The results showed that miR-204 was downregulated, while CXCR4 was upregulated in NPC samples and cells with important functional consequences. Also, miR-204 expression was inversely correlated to CXCR4 expression and it was also associated with the clinicopathologic features. Ectopic expression of miR-204 was significantly suppressed, whereas downregulation of miR-204 facilitated the capacities of NPC cells proliferation, invasion and migration. Besides, it was also found that miR-204 mimic strongly decreased CXCR4 expression and miR-204 inhibitor increased CXCR4 expression. Furthermore, luciferase assay results demonstrated that CXCR4 was the direct target of miR-204. Conversely to miR-204 effect, knockdown of CXCR4 showed an inhibitory effect on NPC cell progression. Mechanistic investigations revealed that miR-204 regulated NF-κB signaling via CXCR4. CONCLUSION: Taken together, our findings suggested that miR-204 regulated NPC progression by targeting CXCR4 through NF-κB signaling pathway.

Identification of Key Modules, Hub Genes, and Noncoding RNAs in Chronic Rhinosinusitis with Nasal Polyps by Weighted Gene Coexpression Network Analysis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with relatively easy recurrence. However, the precise molecular mechanisms of this disease are poorly known. Based on gene sequencing data obtained from the Gene Expression Omnibus (GEO) database, we constructed coexpression networks by weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The core gene of pathogenesis, CRSwNP, was screened by protein-protein interaction data (PPI) from the HPRD database. Unsupervised clustering was applied to screen hub genes related to the phenotype of CRSwNP. Blue and turquoise modules were found to be most significantly related to the pathogenicity of CRSwNP. Functional enrichment analysis showed that cell proliferation in the blue modules, the apoptotic process in the turquoise module, and the cancer pathway in both modules were mostly significantly correlated with the development of CRSwNP. The noncoding RNAs (long noncoding RNA and microRNA) and the top 10 core genes in each module were found to be associated with the pathogenesis of CRSwNP. A total of nine hub genes were identified to be related to the CRSwNP phenotype. By qRT-PCR analysis, AKT1, CDH1, PIK3R1, CBL, LRP1, MALAT1, and XIST were proven to be associated with the pathogenesis of CRSwNP. AGR2, FAM3D, PIP, DSE, and TMC were identified to be related to the CRSwNP phenotype. Further exploration of these genes will reveal more important information about the mechanisms of CRSwNP.

Down-regulation of anti-inflammatory TIPE2 may aggravate adenoidal hypertrophy in children.

Adenoidal hypertrophy (AH) is a common disorder in the pediatric population, with common symptoms including mouth breathing, nasal congestion, hyponasal speech, snoring and obstructive sleep apnea. Although the pathogenesis of AH has not been fully elucidated, recent studies have indicated that immune responses may play an important role in AH. Tumor necrosis factor-alpha (TNF-α)-induced protein-8 like-2 (TIPE2) is a newly identified protein that negatively regulates the activation of inflammatory pathways. Here, we investigated the effect of TIPE2 in AH in children. We observed that the levels of TNF-α and interleukin-6 were greater in the adenoid tissue of AH children than in healthy control subjects (P < 0.01), and this increase was positively correlated with the severity of AH. The level of TIPE2 expression was decreased compared with control and was negatively correlated with AH. TIPE2 overexpression in primary human monocytes (isolated from adenoid tissue of children with AH) inhibited the activation of nuclear factor-κB and the expression of TNF-α and interleukin-6. These results suggest that overexpression of TIPE2 may attenuate AH through inactivation of the nuclear factor-κB signaling pathway.

Corrigendum: Correlation of Bromodomain Protein BRD4 Expression With Epithelial-Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps.

[This corrects the article DOI: 10.3389/fmed.2020.00413.].

Correlation of Bromodomain Protein BRD4 Expression With Epithelial-Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps.

Objectives: This study aimed to explore the relationship between bromodomain-containing protein 4 (BRD4), epithelial-mesenchymal transition (EMT), and disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: We performed immunofluorescent (IF) staining to evaluate the expression of BRD4 in the polyp tissues of CRSwNP and inferior turbinate mucosa of healthy controls. The relationship between BRD4 and EMT was evaluated by the BRD inhibitor JQ1 and BRD4 siRNA in primary human nasal polyp-derived epithelial cells. Disease severity was scored by using the Lund-Mackay scores of paranasal sinus computed tomography (CT) scans. Results: The expression of BRD4 in patients with CRSwNP was significantly higher than that in healthy controls. The loss of BRD4 function by the BRD inhibitor JQ1 and BRD4 siRNA resulted in the reduction of E-cadherin, increasing vimentin, and Snai1 mRNA expression. Moreover, the expression of BRD4 was related to the total CT scan scores (r = 0.4682, P = 0.0210). Conclusions: BRD4 had higher expression in CRSwNP than in healthy controls and might be associated with EMT in CRSwNP. BRD4 mRNA expression was associated with disease severity in CRSwNP.

Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma.

Genetic alteration involving N6-methyladenosine (m6A) regulatory genes is a frequent characteristic of multiple tumors. Nevertheless, little is known regarding their genetic alteration signatures and prognostic values in head and neck squamous cell carcinoma (HNSCC). In this study, RNA sequence profiles and copy number variation (CNV) data of 506 HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Correlation analysis involving alteration of m6A regulatory genes, clinicopathological characteristics, and patient survival was performed using R language. The results suggest that alteration of m6A regulatory genes was correlated with clinical staging. Patients with high expression of ALKBH5, FTO, METTL14, WTAP, YTHDC1, YTHDF1, and YTHDF2 had poor overall survival (OS) than those with low expression. Univariate and multivariate Cox regression analyses showed that ALKBH5 and YTHDC2 were independent risk factors for OS. However, patients with high YTHDC2 expression had better OS. Moreover, according to machine learning results, YTHDC2 was found to be the most important gene among the 10 m6A regulators. Additionally, high expression of YTHDC2 was correlated with activation of apoptosis and ubiquitin-mediated proteolysis. Here, we identified alterations to m6A regulatory genes in HNSCC for the first time and found that seven m6A regulators were associated with poor prognosis, especially ALKBH5, whereas YTHDC2 was associated with better prognosis. These m6A-related regulators could act as novel prognostic biomarkers for HNSCC. Our findings provide clues for understanding RNA epigenetic modifications in HNSCC.