ABSTRACT
BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.
Subject(s)
Blood Pressure , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Blood Pressure/genetics , Gene Expression Profiling , Hypertension/genetics , Transcriptome , Polymorphism, Single Nucleotide , Male , Risk Assessment , Female , Sodium Chloride, Dietary/adverse effectsABSTRACT
The co-storage of two or more Chinese herbal medicines can effectively prevent the herbs from the damage by pests. Thus, it is important to protect herbs and crops to study Chinese herbal medicines and their medicinal components against storage pests. This study aimed to assess the insecticidal activities and repellent effect of essential oils (EOs) extracted from fruits at different periods from Zanthoxylum myriacanthum Wall. ex Hook. f. (1â h, 2â h, 3-5â h and 5-7â h), and their major compounds against three kinds of pests (Tribolium castaneum, Lasioderma serricorne, and Liposcelis bostrychophila). The results of gas chromatography-mass spectrometer analysis revealed homomyrtenol (22.56 %, 28.01 %, 28.48 % and 28.41 %, respectively) and p-cymene (30.58 %, 13.95 %, 24.97 % and 6.85 %, respectively) were the common major compounds of the EOs at 1â h, 2â h, 3-5â h, and 5-7â h. m-Cymene contents in EOs of fruits, 1â h, 2â h and 3-5â h were 3.85 %, 0.95 %, 6.71 %, and 6.15 %, respectively. According to Principal component analysis (PCA), the composition of fruits' EO was significantly different from other EOs due to the different collection times. The bio-assays showed that EOs and major compounds were toxic to all three pests, but the fumigation effect on L. bostrychophila was not noticeable. EOs extracted at different times had a repellent effect on the three pests at the highest concentration (78.63â nL/cm2 ), but the attractive effects of the EOs of 3-5â h, 5-7â h, and p-cymene were observed at the low concentrations (3.15, 0.63 and 0.13â nL/cm2 ). Our results suggest that Z. myriacanthum have the potential to be developed as biological insecticides.
Subject(s)
Insect Repellents , Insecticides , Oils, Volatile , Tribolium , Zanthoxylum , Animals , Insect Repellents/pharmacology , Insecticides/pharmacology , Oils, Volatile/pharmacology , Plant Extracts/pharmacologyABSTRACT
AIMS: The cellular functions of bladder urothelial cells in interstitial cystitis/bladder pain syndrome (IC/BPS) have not been well revealed and understood. Thus, the study aims to identify key genes and significant pathways in urothelium corresponding to IC/BPS in a lipopolysaccharide (LPS)-induced cystitis model and provide novel clues related to diagnosis and treatment of IC/BPS. METHODS: Human urothelial cells (HUCs) were incubated with LPS (50 µg/ml for 24 h). Microarray was applied to analyze the differentially expressed genes (DEGs) between HUCs under LPS treatment and the control group. DEGs in the two groups were identified and then used for enrichment analysis. Subsequently, protein-protein interaction (PPI) network based on DEGs was constructed. Lastly, the top five key genes were identified through the Cytoscape (version 3.7.2) using the "Clustering Coefficient" algorithm. RESULTS: One hundred and seventy-one DEGs (96 upregulated genes and 75 downregulated genes) were identified between the LPS treatment and control group. The established PPI network was composed of 169 nodes and 678 edges. Moreover, C19orf33, TRIM31, MUC21, ELF3, and IFI27 were identified as hub genes in the PPI network. Subsequently, a statistically increased expression level of TRIM31 and ELF3 was validated by real-time quantitative-polymerase chain reaction and immunohistochemistry in bladder tissues from 20 patients with IC/BPS. CONCLUSIONS: TRIM31 and ELF3 may be the two hub genes in urothelium corresponding to IC/BPS. More studies are warranted to further validate the findings. The identified marker genes may be useful targets for further studies to develop diagnostic tools and more effective therapies for a broader group of women with IC/PBS.
Subject(s)
Cystitis, Interstitial , Algorithms , Cystitis, Interstitial/chemically induced , Cystitis, Interstitial/genetics , Female , Humans , Lipopolysaccharides , Tripartite Motif Proteins , Ubiquitin-Protein Ligases , UrotheliumABSTRACT
Deep eutectic solvents (DES) are promising green solvents for depolymerization and reconstruction of lignin. Revealing the transformations of lignin during DES treatment is beneficial for high potential lignin applications. In this study, bagasse lignin was treated with a binary DES and three ternary DESs, respectively. The results showed that net hydrogen bonding acidity(α-ß) value of DES was positively correlated to the increment of phenolic hydroxyl of lignin, and the ternary DES of choline chloride-formic acid-oxalic acid (ChCl-FA-OA) exhibited the best phenolation performances. The phenolic hydroxyl content of ChCl-FA-OA treated lignin was increased by 50.4 %, reaching 2.41 mmol/g under optimum conditions (120 °C, 4 h, ChCl-FA-OA = 1:2:1). Moreover, it was found that the cleavage of ß-O-4' aryl ether bond and ester bond were dominant reactions during the treatment, accompanied by condensation reactions. Additionally, the obtained lignin oil contained various syringyl and guaiacyl derived phenolic compounds. Especially, the content of acetovanillone in lignin oil reached 29.94 %, much higher than in previous studies. Finally, the degradation mechanism of lignin in ChCl-FA-OA system was proposed. The present work provided insights into the relationship between lignin phenolation and DES properties. The novel ChCl-FA-OA system can achieve efficient lignin depolymerization, and convert lignin biomass into value-added chemical products.
Subject(s)
Deep Eutectic Solvents , Lignin , Lignin/chemistry , Solvents/chemistry , Phenols , Choline/chemistry , Biomass , Oxalic Acid , HydrolysisABSTRACT
The adverse effects of relying solely on synthetic pesticides have become increasingly evident, leading many countries to explore alternatives sourced from plant-based green economies. Essential oil (EO) from stems and leaves of Adenosma buchneroides Bonati (A. buchneroides) was distilled by using hydrodistillation and subjected to gas chromatography-mass spectrometry (GC-MS) for component identification. Subsequently, EO as well as its main constituents (thymol and p-cymene) were tested for their insecticidal activity against the red flour beetle (Tribolium castaneum), the cigarette beetle (Lasioderma serricorne), and the booklouse (Liposcelis bostrychophila). The joint action of thymol and p-cymene produced an additive or synergistic effect. A. buchneroides essential oil (BHO) and the fixed ratio of the main compounds, thymol, and p-cymene both showed significant toxic activity against the target pests. This toxic effect is not simply the sum of individual effects, as it is influenced by various factors such as insect species and mode of action. These findings imply that the BHO and its phytoconstituents possess great potential to develop plant-derived biopesticides that will be safe for humans and the environment.
Subject(s)
Coleoptera , Insect Repellents , Insecticides , Oils, Volatile , Tribolium , Animals , Humans , Oils, Volatile/chemistry , Thymol/pharmacology , Insect Repellents/pharmacology , Insecta , Insecticides/chemistryABSTRACT
Alzheimer's disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear. In this study, we demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation. Treating with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) from the Chinese herb Polygonum multiflorum that has been well known for its unique anti-aging effect, learning-memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN-γ induced microglia activation showed that TSG reversed the polarization status of M1-type microglia to restore the quiescence, and cGAS-STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, IFN-α and IFN-ß, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN-γ-stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS-STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS-STING inhibitors. Taken together, our findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS-STING signaling pathway in AD.
Subject(s)
Alzheimer Disease , Stilbenes , Mice , Animals , Alzheimer Disease/drug therapy , Inflammasomes/metabolism , Glycosides , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Neuroinflammatory Diseases , Lipopolysaccharides , Cytokines/metabolism , Nucleotidyltransferases/metabolism , Mice, Transgenic , Stilbenes/pharmacology , Stilbenes/therapeutic useABSTRACT
As an evolutionarily phenotypic conversion program, the epithelial-mesenchymal transition (EMT) has been implicated in tumour deterioration and has facilitated the metastatic ability of cancer cells via enhancing migration and invasion. Gastric cancer (GC) remains a frequently diagnosed non-skin malignancy globally. Most GC-associated mortality can be attributed to metastasis. Recent studies have shown that EMT-related long non-coding RNAs (lncRNAs) play a critical role in GC progression and GC cell motility. In addition, lncRNAs are associated with EMT-related transcription factors and signalling pathways. In the present review, we comprehensively described the EMT-inducing lncRNA molecular mechanisms and functional perspectives of EMT-inducing lncRNAs in GC progression. Taken together, the statements of this review provided a clinical implementation in identifying lncRNAs as potential therapeutic targets for advanced GC.
ABSTRACT
BACKGROUND: YouTube, as a widely used video website around the world, contains a large number of surgical teaching videos, providing a good platform for doctors to learn surgery, but its content and quality are uneven. Tension-free vaginal tape obturator (TVT-O) and trans-obturator vaginal tape (TOT) are common surgical methods for the treatment of stress urinary incontinence (SUI), and there are many videos on YouTube teaching these procedures. We aimed to assess the educational value of surgical videos of TVT-O and TOT on YouTube. METHODS: A comprehensive search was conducted for "tension-free vaginal tape obturator" and "trans-obturator vaginal tape" on YouTube on August 22. After referring to LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) and previous studies, we developed a checklist containing 5 major items and 18 minor items. SPSS 26 was applied to data and correlation analysis. RESULTS: A total of 36 videos were assessed. The average number of days available was 1,956.6 days (range, 190-4,152 days) and the average length was 9.7 min (range, 1.8-73.6 min, SD: 13.65). Video definition is divided into high, moderate and low, accounting for 22%, 36% and 42% respectively. The average score of the included videos was 7.39 (range, 3-16, SD: 3.57). The correlation analysis indicated that the video quality score has a certain correlation with the length of the video, but has no significant correlation with other factors and there was no significant correlation between audience likes and other factors. CONCLUSIONS: On YouTube, we still lack high educational value videos about TVT-O and TOT, and the existing videos are deficient in the explanation of critical steps, the key points of patients' perioperative management, and the application of auxiliary teaching tools. This further indicates the importance of improving educational videos of surgery, and an authoritative checklist for urologic surgery.
ABSTRACT
As a source of aromatic plants, the genus Artemisia has long been considered to have the potential to develop plant pesticides. In this study, components of essential oils from A. dalai-lamae, A. tangutica, A. sieversiana, A. tanacetifolia and A. ordosica were identified by GC-MS. A total of 56 constituents were analysed, and each species consisted of 9 to 24 constituents. Principle component analysis (PCA) revealed that A. dalai-lamae, A. tangutica and A. tanacetifolia are characterised by monoterpene hydrocarbons and oxygenated monoterpenes. Hierarchical cluster analysis (HCA) showed the most remarkable similarity between A. sieversiana and A. ordosica, but the similarity was still lower than 50%. Contact toxicity and repellency of essential oils were evaluated by bioassays; A. ordosica oil exhibited the most substantial contact toxicity (LD50 = 52.11 µg/cm2) against Liposcelis bostrychophila, while A. tangutica oil showed the most potent contact toxicity (LD50 = 17.42 µg/adult) against Tribolium castaneum. Except for A. dalai-lamae, the other four species showed the same level (p > 0.05) of repellent activity as the positive control against both pests at high concentrations. The results indicated that these five Artemisia species had high chemical diversity and great potential to be developed into more effective and environmentally friendly anti-insect agents.
ABSTRACT
Interstitial cystitis (IC) is a severely debilitating and chronic disorder with unclear etiology and pathophysiology, which makes the diagnosis difficult and treatment challenging. To investigate the role of immunity in IC bladders, we sequenced 135,091 CD45+ immune cells from 15 female patients with IC and 9 controls with stress urinary incontinence using single-cell RNA sequencing (scRNA-seq). 22 immune subpopulations were identified in the constructed landscape. Among them, M2-like macrophages, inflammatory CD14+ macrophages, and conventional dendritic cells had the most communications with other immune cells. Then, a significant increase of central memory CD4+ T cells, regulatory T cells, GZMK+CD8+ T cells, activated B cells, un-switched memory B cells, and neutrophils, and a significant decrease of CD8+ effector T cells, Th17 cells, follicular helper T cells, switched memory B cells, transitional B cells, and macrophages were noted in IC bladders. The enrichment analysis identified a virus-related response during the dynamic change of cell proportion, furthermore, the human polyomavirus-2 was detected with a positive rate of 95% in urine of patients with IC. By integrating the results of scRNA-seq with spatial transcriptomics, we found nearly all immune subpopulations were enriched in the urothelial region or located close to fibroblasts in IC bladders, but they were discovered around urothelium and smooth muscle cells in control bladders. These findings depict the immune landscape for IC and might provide valuable insights into the pathophysiology of IC.
Subject(s)
Cystitis, Interstitial , CD8-Positive T-Lymphocytes , Cystitis, Interstitial/genetics , Female , Humans , Sequence Analysis, RNA , Transcriptome/genetics , UrotheliumABSTRACT
The treatment with 2nd-generation tyrosine kinase inhibitors (2G-TKIs), namely, dasatinib and nilotinib, has been reported to have faster and deeper responses in newly diagnosed chronic phase-chronic myeloid leukemia (CP-CML) patients as compared with imatinab. A number of studies on the discontinuation of 2G-TKIs have been conducted and recently published. A meta-analysis was conducted in this study to assess the rate of treatment-free remission (TFR) rate as well as the long-term safety of 2G-TKI discontinuation in CML patients with stable deep molecular response (DMR). 517 patients were recruited in 5 single-armed, prospective cohort studies. The overall weighted mean TFR rate at the follow-up of 12 months reached 57% (95% CI 51-64%; I 2 = 56.4%). The weighted mean TFR rate at the 24-month follow-up was 53% (95% CI 47-60%; I 2 = 47.1%). The loss of TFR was primarily concentrated in the first 12 months. 96.5% of patients, having restarted TKI therapy after a molecular relapse, achieved major molecular response (MMR) rapidly. There were four deaths at the two-year follow-up. As suggested from the results of the final study, 2G-TKI discontinuation in CML patients with stable DMR was reported to be feasible. Relapsed patients were retreated with 2G-TKI, and over 95% of patients could reach MMR. Almost no deaths occurred due to adverse events in two years after discontinuation, and more than half of the patients could maintain a TFR.
Subject(s)
Antineoplastic Agents/administration & dosage , Leukemia, Myeloid, Chronic-Phase/drug therapy , Protein Kinase Inhibitors/administration & dosage , Computational Biology , Dasatinib/administration & dosage , Disease-Free Survival , Duration of Therapy , Female , Humans , Imatinib Mesylate/administration & dosage , Male , Pyrimidines/administration & dosage , Recurrence , Remission InductionABSTRACT
Benzo [a]pyrene (BaP) is a model compound for the study of polycyclic aromatic hydrocarbon (PAH) carcinogenesis. Upon metabolism, BaP is metabolized to the ultimate metabolite, BaP trans-7,8-diol-anti-9,10-epoxide (BPDE), that reacts with cellular DNA to form BPDE-dG adducts responsible for BaP-induced mutagenicity, carcinogenicity, and teratogenicity. In this study, we employed our developed LC-MS/MS method to detect and quantity BPDE-dG adducts present in 42 normal human umbilical cord blood samples and 42 birth defect cases. We determined that there is no significant difference in the level of BPDE-dG formation between the normal and birth defect groups. This represents the first time to use an LC-MS/MS method to quantify BPDE-dG in human umbilical blood samples. The results indicated that under experimental conditions, BPDE-dG adducts were detected in all the human umbilical cord blood samples from the normal and birth defect groups.