Nur77 is involved in the regulation of obesity-related lower muscle mass by promoting Pten degradation.

Obesity may impair muscle function and is sometimes associated with lower muscle mass. However, the internal regulatory mechanism is still unclear. Nur77 has been reported to improve obesity phenotype by regulating glucose and lipid metabolism and inhibiting the production of inflammatory factors and reactive oxygen species. Concurrently, Nur77 also plays an important role in muscle differentiation and development. We aimed to investigate the role of Nur77 in obesity-related lower muscle mass. Our in vivo and in vitro experiments illustrated that the reduction of obesity-related Nur77 accelerated the occurrence of lower muscle mass by interfering with the signaling pathways involved in the regulation of myoprotein synthesis and degradation. We further demonstrated that Nur77 activates the PI3K/Akt pathway by promoting Pten degradation, which enhances the phosphorylation of the Akt/mTOR/p70S6K pathway and inhibits the expression of skeletal muscle-specific E3 ligases (MAFbx/MuRF1). Nur77 induces Pten degradation by increasing the transcription of its specific E3 ligase Syvn1. Our study confirms that Nur77 is a key factor in ameliorating obesity-related lower muscle mass, providing a new therapeutic target and theoretical basis for the treatment of obesity-related lower muscle mass.

Chemical methods to remove microplastics from wastewater: A review.

Microplastics (Mps) have emerged as a pervasive environmental concern, with their presence detected not only in freshwater ecosystems but also in drinking and bottled water sources. While extensive research has centered on understanding the origins, migration patterns, detection techniques, and ecotoxicological impacts of these contaminants, there remains a notable research gap about the strategies for Mps removal. This study reviews existing literature on chemical approaches for mitigating microplastic contamination within wastewater systems, focusing on coagulation precipitation, electrocoagulation, and advanced oxidation methods. Each approach is systematically explored, encompassing their respective mechanisms and operational dynamics. Furthermore, the comparative analysis of these three techniques elucidates their strengths and limitations in the context of MPs removal. By shedding light on the intricate mechanisms underlying these removal methods, this review contributes to the theoretical foundation of microplastic elimination from wastewater and identifies future research trajectories and potential challenges.

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival.

The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosin staining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-ß1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-ß1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.

Towards advanced removal of organics in persulfate solution by heterogeneous iron-based catalyst: A review.

Heterogeneous iron-based catalysts have drawn increasing attention in the advanced oxidation of persulfates due to their abundance in nature, the lack of secondary pollution to the environment, and their low cost over the last a few years. In this paper, the latest progress in the research on the activation of persulfate by heterogeneous iron-based catalysts is reviewed from two aspects, in terms of synthesized catalysts (Fe0, Fe2O3, Fe3O4, FeOOH) and natural iron ore catalysts (pyrite, magnetite, hematite, siderite, goethite, ferrohydrite, ilmenite and lepidocrocite) focusing on efforts made to improve the performance of catalysts. The advantages and disadvantages of the synthesized catalysts and natural iron ore were summarized. Particular interests were paid to the activation mechanisms in the catalyst/PS/pollutant system for removal of organic pollutants. Future research challenges in the context of field application were also discussed.

Separation and identification of cetirizine enantiomers in human urine by capillary electrophoresis and circular dichroism independent of their standards.

Enantioseparation and determination of chiral drugs are of vital importance in biochemical and pharmaceutical research due to the different biological activity, mechanism, and toxicity of individual enantiomers. As a second-generation H(1)-antagonist, cetirizine's pharmaceutical activity is mainly derived from the levocetirizine while the dextro-enantiomer is ineffective and even associated with side effects. Herein, the enantiomers of cetirizine were separated by capillary electrophoresis and identified by electronic circular dichroism. Satisfactory linear relationship was found between the circular dichroism signal at λmax and the electrophoretic peak area difference in the nonracemic mixture of enantiomers. It made possible identification and quantification of cetirizine enantiomers independent of single enantiomer standards. The method's feasibility was demonstrated on the enantiomeric excess experiments of oral drugs measured in human blank urine. Additionally, the separation and determination of cetirizine in human urine after administration were also realized by capillary electrophoresis, indicating the method was sensitive enough for pharmacokinetic study.

LncIMF2 promotes adipogenesis in porcine intramuscular preadipocyte through sponging MiR-217.

Intramuscular fat is positively related to meat quality including tenderness, flavor, and juiciness. Long noncoding RNA (LncRNA) plays a vital role in regulating adipogenesis. However, it is largely unknown about lncRNAs associated with porcine intramuscular adipocyte adipogenesis. In the present study, we focus on a novel LncRNA, which is named lncIMF2, associated with adipogenesis by our previous RNA-sequence analysis and bioinformatics analysis. We demonstrated LncIMF2 knockdown inhibited the proliferation of porcine intramuscular adipocytes while expression of cell cycle-related genes was decreased. Besides, we found LncIMF2 knockdown inhibited expression of adipogenic differentiation marker genes including PPARγ (Peroxisome proliferator-activated reporter gamma) and ATGL (Adipose triglyceride lipase). Similarly, overexpression of LncIMF2 promotes proliferation and differentiation of porcine intramuscular preadipocytes. Moreover, we proved that IncIMF2 acts as a molecular sponge for MicroRNA-217 (miR-217), which has been found associated with adipogenesis, thereby affecting the expression of the miR-217 target gene. Collectively, our findings will contribute to a deeper understanding of the role of LncRNA in pig IMF deposition for the improvement of meat quality.

Naringin protects against inflammation and apoptosis induced by intestinal ischemia-reperfusion injury through deactivation of cGAS-STING signaling pathway.

Effective amelioration of ischemia/reperfusion (I/R)-induced intestinal injury and revealing its mechanisms remain the challenges in both preclinic and clinic. Potential mechanisms of naringin in ameliorating I/R-induced intestinal injury remain unknown. Based on pre-experiments, I/R-injured rat intestine in vivo and hypoxia-reoxygenation (H/R)-injured IEC-6 cells in vitro were used to verify that naringin-alleviated I/R-induced intestinal injury was mediated via deactivating cGAS-STING signaling pathway. Naringin improved intestinal damage using hematoxylin and eosin staining and decreased alanine aminotransferase and aspartate aminotransferase contents in plasma. Naringin decreased inflammation characterized by reducing IL-6, IL-1ß, TNF-α, and IFN-ß contents in both plasma and IEC-6 cells. Naringin mitigated oxidative stress via recovering superoxide dismutase, glutathione, and malondialdehyde levels in the I/R-injured intestine. Naringin reduced the expression of apoptotic proteins, including Bax, caspase-3, and Bcl-2, and reduced terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells both in vivo and in vitro, and decreased Hoechst 33342 signals in vitro. cGAS, STING, p-TBK1, p-IRF3, and NF-κB expressions were up-regulated both in vivo and in vitro respectively and the up-regulated indexes were reversed by naringin. Transfection of cGAS-siRNA and cGAS-cDNA significantly down-regulated and up-regulated cGAS-STING signaling-related protein expressions, respectively, and partially weakened naringin-induced amelioration on these indexes, suggesting that deactivation of cGAS-STING signaling is the crucial target for naringin-induced amelioration on I/R-injured intestine.

Nur77 Prevents Osteoporosis by Inhibiting the NF-κB Signalling Pathway and Osteoclast Differentiation.

Inflammation is a major risk factor for osteoporosis, and reducing inflammatory levels is important for the prevention of osteoporosis. Although nuclear receptor 77 (Nur77) protects against inflammation in a variety of diseases, its role in osteoporosis is unknown. Therefore, the main purpose of this study was to investigate the osteoprotective and anti-inflammatory effects of Nur77. The microCT and haematoxylin and eosin staining results indicated that knockout of Nur77 accelerated femoral bone loss in mice. The enzyme-linked immunosorbent assay (ELISA) results showed that knockout of Nur77 increased the serum levels of hsCRP and IL-6. The expression levels of NF-κB, IL-6, TNF-α and osteoclastogenesis factors (TRAP, NFATC1, Car2, Ctsk) in the femurs of Nur77 knockout mice were increased significantly. Furthermore, in vitro, shNur77 promoted the differentiation of RAW264.7 cells into osteoclasts by activating NF-κB, which was confirmed by PDTC treatment. Mechanistically, Nur77 inhibited osteoclast differentiation by inducing IκB-α and suppressing IKK-ß. In RAW264.7 cells, overexpression of Nur77 alleviated inflammation induced by siIκB-α, while siIKK-ß alleviated inflammation induced by shNur77. Consistent with the in vivo studies, we found that compared with control group, older adults with high serum hsCRP levels were more likely to suffer from osteoporosis (OR = 1.76, p < 0.001). Our data suggest that Nur77 suppresses osteoclast differentiation by inhibiting the NF-κB signalling pathway, strongly supporting the notion that Nur77 has the potential to prevent and treat osteoporosis.

Risk SNP-mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway.

As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNA dysfunction and even cancer. Nevertheless, studies on the association between lncRNA-associated single-nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22-1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95% CI: 1.15-1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA-616-3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR-616-3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.

The effects of oral health and social support on health-related quality of life of migrant older with children in Weifang, China.

BACKGROUND: With the accelerated urbanization and aging population in China, more and more migrant older with children (MOC) moved to new cities. Previous studies mainly explored the acculturation of MOC, yet few focused on the health conditions of this vulnerable group. This study aimed to investigate the effects of oral health and social support on health-related quality of life (HRQOL) of MOC in Weifang, China. METHOD: This study was a cross-sectional study and participants were selected by multi-stage cluster random sampling in Weifang, China. The HRQOL was assessed via the 12-item Short-Form Health Survey (SF-12) which included the mental component summary (MCS) and the physical component summary (PCS). The oral health was evaluated by the Geriatric Oral Health Assessment Index (GOHAI). The social support was administered using the Social Support Rating Scale (SSRS). Descriptive analysis was used to describe participants' sociodemographic variables, oral health and social support. Univariate analysis and binary logistic regression analysis was used to investigate the association between the social support, oral health and HRQOL. RESULTS AND DISCUSSION: It was found that 25.0% of MOC were defined as MCS poor and PCS poor, respectively. Those participants with average and low monthly household income compared to those around them, average and poor oral health, and low levels of social support were more likely to have poor PCS. Those with temporary residence permits, fair and poor oral health, and medium and low levels of social support were more likely to report poor MCS. CONCLUSION: Results indicated that better social support and oral health led to higher HRQOL of MOC. Implications for the government, communities and families of MOC were given to improve their HRQOL.

The mediating effect of social support on the association between socioeconomic status and self-reported oral health status among the migrant elderly following children in Weifang, China: a cross-sectional study.

BACKGROUND: Driven by population aging and the rapid urbanization in China, many migrant elderly following children (MEFC) moved to big cities to care for their grandchildren. The purpose of this study is to clarify the mediating effect of social support on the relationship between socioeconomic status (SES) and self-reported oral health status among the MEFC in Weifang, China. METHODS: Multistage cluster random sampling was used to select the participants and finally 613 MEFC were included in the survey. The Social Support Rating Scale (SSRS) and the Chinese version of the Geriatric Oral Health Assessment Index (GOHAI) scale were used for data collection. Descriptive analysis, Rao-Scott test, t-test and structural equation modeling (SEM) were conducted in this study. RESULTS: Mean score of GOHAI of the MEFC was 54.95 ± 6.47. The SES of MEFC exerted positive direct effect both on social support (standardized coefficient = 0.15) and self-reported oral health status (standardized coefficient = 0.22); social support exerted positive direct effect on self-reported oral health status (standardized coefficient = 0.17). Social support partially mediated the association between SES and self-reported oral health status [95% confidence interval (CI) 0.003-0.064, P < 0.05], and the mediating effect of social support accounted for 12.0% of the total effect. CONCLUSIONS: Higher GOHAI score of MEFC indicated their better self-reported oral health status. MEFCs' SES could exert positive effect both on social support and self-reported oral health status, while the mediating effect of social support between SES and self-reported oral health status of MEFC was established.

[Screening, domestication and identification of intestinal uric acid degrading bacteria in low uric acid population].

As the largest ecosystem of human body, intestinal microorganisms participate in the synthesis and metabolism of uric acid. Developing and utilizing intestinal bacteria to degrade uric acid might provide new ideas for the treatment of hyperuricemia. The fecal samples of people with low uric acid were inoculated into uric acid selective medium with the concentration of 1.5 mmol/L for preliminary screening, and the initially screened strains that may have degradation ability were domesticated by concentration gradient method, and the strains with high uric acid degradation rate were identified by 16S rRNA sequencing method. A strain of high-efficiency uric acid degrading bacteria was screened and domesticated from the feces of people with low uric acid. The degradation rate of uric acid could reach 50.2%. It was identified as Escherichia coli. The isolation and domestication of high efficient uric acid degrading strains can not only provide scientific basis for the study of the mechanism of intestinal microbial degradation of uric acid, but also reserve biological strains for the treatment of hyperuricemia and gout in the future.

Genetic variants of cell cycle pathway genes are associated with head and neck squamous cell carcinoma in the Chinese population.

Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case-control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (Ptrend < 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T>C reduced the stability of E2F2 3'-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e-8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02-1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3, and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells.

Chryseobacterium endalhagicum sp. nov., isolated from seed of leguminous plant.

A Gram-stain-negative, yellow-pigmented bacterium, designated as L7T, was isolated from seeds of Alhagi sparsifolia Shap., a leguminous plant that grows in northwest PR China. Strain L7T was found to be non-flagellated, non-spore forming rods which can grow at 10-37 °C, pH 6.0-8.5 and in 0-3 % (v/w) NaCl concentration. The 16S rRNA gene sequence analysis showed that strain L7T belongs to the genus Chryseobacterium with sequence similarities to Chryseobacterium vietnamense GIMN1.005T (98.1%), C. bernardetii NCCTC13530T (98.0%), C. vrystaatense LMG 22846T (97.9%), C. nakagawai NCTC13529T (97.7%), C. shigense DSM 17126T (97.6%) and C. rhizosphaerae RSB3-1T (97.5%). The average nucleotide identity of strain L7T to 31 reference strains were 78.6-85.6 %, lower than the species delineation threshold of 95 %. MK-6 was the only respiratory quinone of L7T and major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 1 ω7c and/or C16 : 1 ω6c, isoC17 : 1 ω9c and/or C16 : 0 10-methyl. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminophospholipids, two unidentified aminolipids, three unidentified glycolipids and two unidentified lipids. The G+C content of the genome was 38.58 mol%. On the basis of polyphasic taxonomy analyses in this study, strain L7T is considered to represent a novel species in the genus Chryseobacterium, for which the name Chryseobacterium endalhagicum sp. nov. is proposed. The type strain is L7T (=MCCC 1K05687T=JCM 34506T).

The Molecular Mechanisms of Phytophthora infestans in Response to Reactive Oxygen Species Stress.

Reactive oxygen species (ROSs) are critical for the growth, development, proliferation, and pathogenicity of microbial pathogens; however, excessive levels of ROSs are toxic. Little is known about the signaling cascades in response to ROS stress in oomycetes such as Phytophthora infestans, the causal agent of potato late blight. Here, P. infestans was used as a model system to investigate the mechanism underlying the response to ROS stress in oomycete pathogens. Results showed severe defects in sporangium germination, mycelium growth, appressorium formation, and virulence of P. infestans in response to H2O2 stress. Importantly, these phenotypes mimic those of P. infestans treated with rapamycin, the inhibitor of target of rapamycin (TOR, 1-phosphatidylinositol-3-kinase). Strong synergism occurred when P. infestans was treated with a combination of H2O2 and rapamycin, suggesting that a crosstalk exists between ROS stress and the TOR signaling pathway. Comprehensive analysis of transcriptome, proteome, and phosphorylation omics showed that H2O2 stress significantly induced the operation of the TOR-mediated autophagy pathway. Monodansylcadaverine staining showed that in the presence of H2O2 and rapamycin, the autophagosome level increased in a dosage-dependent manner. Furthermore, transgenic potatoes containing double-stranded RNA of TOR in P. infestans (PiTOR) displayed high resistance to P. infestans. Therefore, TOR is involved in the ROS response and is a potential target for control of oomycete diseases, because host-mediated silencing of PiTOR increases potato resistance to late blight.

Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease in reproductive women, and the endocrine levels are also affected by diseases. The aim of this study was to determine the effect of thrombospondin-1 (TSP-1) on PCOS rat model. METHODS: We established the PCOS rat model, the serum hormones including TSP-1 expression were determined and morphological characteristics were investigated to evaluate the model. These above endocrine and morphological features were investigated again to evaluate the effect of TSP-1 treatment. RESULTS: In the PCOS model group, the serum hormones change (higher luteinizing hormone, testosterone and estrogen) and decreased TSP-1 expression levels were found compared with the control group. Besides, the morphological characteristics of PCOS were also observed in the model group. After TSP-1 treatment, the higher TSP-1, ANGPT2, PDGFB and PDGFD expression levels, the lower LH and T levels, decreased vessel density as well as VEGFA and ANGPT1 expression levels were found compared with the control group, and the ovary morphological changes were also observed in the TSP-1 experimental group. CONCLUSIONS: TSP-1 delivery system might be an alternative therapy for PCOS treatment.

VdNPS, a Nonribosomal Peptide Synthetase, Is Involved in Regulating Virulence in Verticillium dahliae.

Nonribosomal peptide synthetases (NPS) are known for the biosynthesis of antibiotics, toxins, and siderophore production. They are also a virulence determinant in different phytopathogens. However, until now, the functional characterization of NPS in Verticillium dahliae has not been reported. Deletion of the NPS gene in V. dahliae led to the decrease of conidia, microsclerotia, and pathogenicity. ΔVdNPS strains were tolerant to H2O2, and the genes involved in H2O2 detoxification, iron/copper transport, and cytoskeleton were differentially expressed in ΔVdNPS. Interestingly, ΔVdNPS strains exhibited hypersensitivity to salicylic acid (SA), and the genes involved in SA hydroxylation were up-regulated in ΔVdNPS compared with wild-type V. dahliae under SA stress. Additionally, during infection, ΔVdNPS induced more pathogenesis-related gene expression, higher reactive oxygen species production, and stronger SA-mediated signaling transduction in host to overcome pathogen. Uncovering the function of VdNPS in pathogenicity could provide a reliable theoretical basis for the development of cultivars with durable resistance against V. dahliae-associated diseases.

Identification and Quantitation of Enantiomers by Capillary Electrophoresis and Circular Dichroism Independent of Single Enantiomer Standard.

Identification and quantitation of enantiomers is a critical and challenging step in the process of chiral capillary electrophoresis (CE) analysis, especially when the optically pure enantiomers are expensive or commercially unavailable. Herein, a method of CE in combination with circular dichroism (CD) spectroscopy for the identification of enantiomeric peak independent of single enantiomer standard was proposed. By comparing the theoretical CD spectrum of the single enantiomer calculated by time-dependent density functional theory (TDDFT) with the experimental CD spectrum of the enantiomeric mixture, the configuration of the dominant enantiomer in the nonracemic mixture was determined. Considering that the dominant enantiomer showed bigger peak area on the CE electrophoretogram, the enantiomeric peak was easily identified. Three kinds of enantiomers including seven chiral compounds (i.e., tryptophan, tyrosine, phenylalanine, Boc-valine, Boc-leucine, ibuprofen, and naproxen) were used to evaluate the reliability of the method. The concentration of the single enantiomer in the mixture can be further accurately quantified based on the total concentration of the mixture and the peak area ratio of a couple of enantiomers, and the accuracy was assessed by taking ibuprofen as an example. The developed CE-CD method provides an alternative tool for the analysis of nonracemic mixture with good ECD signals.

TET2 rs2454206, TET2 rs12498609 and ASXL1 rs3746609 single nucleotide polymorphisms in patients with myelodysplastic syndromes.

To study the association between TET2rs2454206, TET2rs12498609 and ASXL1rs3746609 and Myelodysplastic syndromes (MDS), a total of 90 MDS patients and 143 healthy volunteers were included. The clinical data, bone marrow samples of patients and peripheral blood samples of volunteers were obtained. We found TET2rs2454206 G/A genotype, TET2rs12498609 G/C genotype and ASXL1rs3746609 A/G genotype in 13.3%, 11.1%, 10.1% MDS patients and in 42.7%, 22.4%, 23.8% healthy volunteers (P < 0.001; P = 0.029; P = 0.009, respectively). TET2 rs2454206 G/A genotype was associated with higher serum LDH level in MDS (P = 0.025). Patients with TET2rs12498609 G/C genotype were characterized with higher frequency of mutated SRSF2 gene (P = 0.042) and lower occurrence rate of anemia (P = 0.026) than those with C/C genotype. ASXL1rs3746609 A/G genotype linked with higher thrombocyte counts (P = 0.02) and percent of total T lymphocyte (P = 0.029), whereas with lower percent of NK cell (P = 0.032) and B lymphocyte (P = 0.007). None of these three SNPs had impact on the overall survival and disease progression to AML. We concluded that People with TET rs2454206 G/A genotype, TET2rs12498609 G/C genotype or ASXL1rs3746609 A/G genotype were related to lower prevalence of MDS. All of the three SNPs were associated with certain laboratory features in MDS patients.

Identification and comparative oridonin metabolism in different species liver microsomes by using UPLC-Triple-TOF-MS/MS and PCA.

Oridonin (ORI) is an active natural ent-kaurene diterpenoid ingredient with notable anti-cancer and anti-inflammation activities. Currently, a strategy was developed to identify metabolites and to assess the metabolic profiles of ORI in vitro using ultra-high-performance liquid chromatography-Triple/time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS). Meanwhile, the metabolism differences of ORI in the liver microsomes of four different species were investigated using a principal component analysis (PCA) based on the metabolite absolute peak area values as the variables. Based on the proposed methods, 27 metabolites were structurally characterized. The results indicate that ORI is universally metabolized in vitro, and the metabolic pathway mainly includes dehydration, hydroxylation, di-hydroxylation, hydrogenation, decarboxylation, and ketone formation. Overall, there are obvious inter-species differences in types and amounts of ORI metabolites in the four species. These results will provide basic data for future pharmacological and toxicological studies of ORI and for other ent-kauranes diterpenoids. Meanwhile, studying the ORI metabolic differences helps to select the proper animal model for further pharmacology and toxicological assessment.