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1.
J Proteome Res ; 23(7): 2532-2541, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38902972

ABSTRACT

Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.


Subject(s)
Angiopoietin-Like Protein 7 , Angiopoietin-like Proteins , Aqueous Humor , Biomarkers , Wet Macular Degeneration , Aqueous Humor/metabolism , Humans , Biomarkers/metabolism , Male , Wet Macular Degeneration/metabolism , Wet Macular Degeneration/genetics , Female , Angiopoietin-like Proteins/metabolism , Angiopoietin-like Proteins/genetics , Choroidal Neovascularization/metabolism , Choroidal Neovascularization/genetics , Choroidal Neovascularization/pathology , Aged , Cell Proliferation , Animals , Cell Movement , Mice
2.
J Transl Med ; 22(1): 562, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867291

ABSTRACT

BACKGROUND: Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated patients fail to derive benefits from intravitreal injections. tRNA-derived small RNA (tsRNA) emerges as a crucial class of non-coding RNA molecules, orchestrating key roles in the progression of human diseases by modulating multiple targets. Through our prior sequencing analyses and bioinformatics predictions, tRNA-Cys-5-0007 has shown as a potential regulator of ocular angiogenesis. This study endeavors to elucidate the precise role of tRNA-Cys-5-0007 in the context of ocular angiogenesis. METHODS: Quantitative reverse transcription PCR (qRT-PCR) assays were employed to detect tRNA-Cys-5-0007expression. EdU assays, sprouting assays, transwell assays, and Matrigel assays were conducted to elucidate the involvement of tRNA-Cys-5-0007 in endothelial angiogenic effects. STZ-induced diabetic model, OIR model, and laser-induced CNV model were utilized to replicate the pivotal features of ocular vascular diseases and evaluate the influence of tRNA-Cys-5-0007 on ocular angiogenesis and inflammatory responses. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were employed to elucidate the anti-angiogenic mechanism of tRNA-Cys-5-0007. Exosomal formulation was employed to enhance the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. RESULTS: tRNA-Cys-5-0007 expression was down-regulated under angiogenic conditions. Conversely, tRNA-Cys-5-0007 overexpression exhibited anti-angiogenic effects in retinal endothelial cells, as evidenced by reduced proliferation, sprouting, migration, and tube formation abilities. In diabetic, laser-induced CNV, and OIR models, tRNA-Cys-5-0007 overexpression led to decreased ocular vessel leakage, inhibited angiogenesis, and reduced ocular inflammation. Mechanistically, these effects were attributed to the targeting of vascular endothelial growth factor A (VEGFA) and TGF-ß1 by tRNA-Cys-5-0007. The utilization of an exosomal formulation further potentiated the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. CONCLUSIONS: Concurrent targeting of tRNA-Cys-5-0007 for anti-angiogenic and anti-inflammatory therapy holds promise for enhancing the effectiveness of current anti-angiogenic therapy.


Subject(s)
Angiogenesis Inhibitors , Anti-Inflammatory Agents , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Humans , RNA, Transfer/metabolism , RNA, Transfer/genetics , Mice, Inbred C57BL , Cell Proliferation/drug effects , Choroidal Neovascularization/pathology , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/metabolism , Male , Eye Diseases/drug therapy , Eye Diseases/pathology , Eye Diseases/metabolism , Diabetes Mellitus, Experimental/drug therapy , Neovascularization, Pathologic , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/pathology , Diabetic Retinopathy/metabolism , Mice , Human Umbilical Vein Endothelial Cells/metabolism
3.
BMC Gastroenterol ; 24(1): 176, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773485

ABSTRACT

BACKGROUND: Angiogenesis is a critical step in colorectal cancer growth, progression and metastasization. CT are routine imaging examinations for preoperative clinical evaluation in colorectal cancer patients. This study aimed to investigate the predictive value of preoperative CT enhancement rate (CER) and CT perfusion parameters on angiogenesis in colorectal cancer, as well as the association of preoperative CER and CT perfusion parameters with serum markers. METHODS: This retrospective analysis included 42 patients with colorectal adenocarcinoma. Median of microvessel density (MVD) as the cut-off value, it divided 42 patients into high-density group (MVD ≥ 35/field, n = 24) and low-density group (MVD < 35/field, n = 18), and 25 patients with benign colorectal lesions were collected as the control group. Statistical analysis of CER, CT perfusion parameters, serum markers were performed in all groups. Receiver operating curves (ROC) were plotted to evaluate the diagnostic efficacy of relevant CT perfusion parameters for tumor angiogenesis; Pearson correlation analysis explored potential association between CER, CT perfusion parameters and serum markers. RESULTS: CER, blood volume (BV), blood flow (BF), permeability surface (PS) and carbohydrate antigen 19 - 9 (CA19-9), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), trefoil factor 3 (TFF3), vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma were significantly higher than those in the control group, the parameters in high-density group were significantly higher than those in the low-density group (P < 0.05); however, the time to peak (TTP) of patients in colorectal adenocarcinoma were significantly lower than those in the control group, and the high-density group showed a significantly lower level compared to the low-density group (P < 0.05). The combined parameters BF + TTP + PS and BV + BF + TTP + PS demonstrated the highest area under the curve (AUC), both at 0.991. Pearson correlation analysis showed that the serum levels of CA19-9, CA125, CEA, TFF3, and VEGF in patients showed positive correlations with CER, BV, BF, and PS (P < 0.05), while these indicators exhibited negative correlations with TTP (P < 0.05). CONCLUSIONS: Some single and joint preoperative CT perfusion parameters can accurately predict tumor angiogenesis in colorectal adenocarcinoma. Preoperative CER and CT perfusion parameters have certain association with serum markers.


Subject(s)
Adenocarcinoma , Carcinoembryonic Antigen , Colorectal Neoplasms , Neovascularization, Pathologic , Predictive Value of Tests , Tomography, X-Ray Computed , Humans , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Colorectal Neoplasms/blood supply , Male , Female , Retrospective Studies , Middle Aged , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/blood , Adenocarcinoma/pathology , Adenocarcinoma/blood supply , Aged , Neovascularization, Pathologic/diagnostic imaging , Neovascularization, Pathologic/blood , Tomography, X-Ray Computed/methods , Carcinoembryonic Antigen/blood , Biomarkers, Tumor/blood , Adult , Microvascular Density , CA-19-9 Antigen/blood , ROC Curve , Vascular Endothelial Growth Factor A/blood , Blood Volume , Preoperative Care/methods
4.
BMJ ; 385: e078218, 2024 04 10.
Article in English | MEDLINE | ID: mdl-38808490

ABSTRACT

OBJECTIVE: To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression. DESIGN: Randomised, double blind, placebo controlled trial with two parallel arms. SETTING: Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022. PARTICIPANTS: 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery. INTERVENTIONS: Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped. MAIN OUTCOME MEASURES: The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth. RESULTS: A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference -3, 95% CI -4 to -2; P<0.001) and 42 days (-3, -4 to -2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (-4, -6 to -3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment. CONCLUSIONS: For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04414943.


Subject(s)
Depression, Postpartum , Ketamine , Humans , Female , Ketamine/administration & dosage , Ketamine/adverse effects , Adult , Double-Blind Method , Pregnancy , Depression, Postpartum/drug therapy , Depression, Postpartum/prevention & control , Antidepressive Agents/administration & dosage , Antidepressive Agents/therapeutic use , Antidepressive Agents/adverse effects , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/prevention & control , China/epidemiology , Treatment Outcome , Pregnancy Complications/psychology , Pregnancy Complications/drug therapy , Psychiatric Status Rating Scales , Mothers/psychology
5.
Plant J ; 116(6): 1717-1736, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37751381

ABSTRACT

Wheat yellow mosaic virus (WYMV) causes severe wheat viral disease in Asia. However, the viral suppressor of RNA silencing (VSR) encoded by WYMV has not been identified. Here, the P1 protein encoded by WYMV RNA2 was shown to suppress RNA silencing in Nicotiana benthamiana. Mutagenesis assays revealed that the alanine substitution mutant G175A of P1 abolished VSR activity and mutant Y10A VSR activity remained only in younger leaves. P1, but not G175A, interacted with gene silencing-related protein, N. benthamiana calmodulin-like protein (NbCaM), and calmodulin-binding transcription activator 3 (NbCAMTA3), and Y10A interacted with NbCAMTA3 only. Competitive Bimolecular fluorescence complementation and co-immunoprecipitation assays showed that the ability of P1 disturbing the interaction between NbCaM and NbCAMTA3 was stronger than Y10A, Y10A was stronger than G175A. In vitro transcript inoculation of infectious WYMV clones further demonstrated that VSR-defective mutants G175A and Y10A reduced WYMV infection in wheat (Triticum aestivum L.), G175A had a more significant effect on virus accumulation in upper leaves of wheat than Y10A. Moreover, RNA silencing, temperature, and autophagy have significant effects on the accumulation of P1 in N. benthamiana. Taken together, WYMV P1 acts as VSR by interfering with calmodulin-associated antiviral RNAi defense to facilitate virus infection in wheat, which has provided clear insights into the function of P1 in the process of WYMV infection.


Subject(s)
Mosaic Viruses , Virus Diseases , RNA Interference , Triticum/genetics , Calmodulin/genetics , Virus Diseases/genetics , Mosaic Viruses/genetics , Plant Diseases/genetics
6.
Ann Transl Med ; 10(20): 1107, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36388810

ABSTRACT

Background: This study aimed to investigate the efficacy and safety of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors in the treatment of advanced cervical cancer and the effect of optimal combination timing on prognosis. Methods: From March 2020 to December 2021, the clinical data of 116 patients with advanced cervical cancer who received PD-1 inhibitors combined with chemotherapy were collected. The clinical characteristics and adverse events of the patients were recorded until the cut-off date of follow-up. The primary endpoints were progression-free survival (PFS), the objective response rate (ORR), and safety; the secondary endpoints were the disease-control rate (DCR) and overall survival (OS). Multivariate Cox proportional hazards regression was used to analyze the prognostic factors affecting the PFS of patients and to assess the effect of the timing of combination therapies on PFS. Results: In total, 85 patients from 4 study centers were included in this study. The median PFS was 10.3 months [95% confidence interval (CI): 9.47-11.13 months], the ORR was 44.7%, the DCR was 75.3%, and the median OS was not reached. The multivariate Cox proportional hazards regression analysis showed that the early combination of chemotherapy with a PD-1 inhibitor provided better PFS than the late combination [hazard ratio (HR) 0.40, 95% CI: 0.24-0.67, P=0.001]. Lymph node metastasis (HR 2.04, 95% CI: 1.24-3.38, P=0.005), and previous treatment (HR 1.79, 95% CI: 1.09-3.00, P=0.023) were also independent risk factors for PFS. During the treatment and follow-up periods, the overall incidence of adverse events in this study was 56.5%, and that of grade ≥3 adverse events was 12.9%. Thrombocytopenia, neutropenia, anemia, and hypothyroidism were the main treatment-related adverse events, all of which were tolerated, and no serious adverse events leading to death were observed. There were no treatment-related deaths. Conclusions: PD-1 inhibitors combined with chemotherapy have good efficacy and controllable safety in patients with advanced cervical cancer. The early combination of PD-1 inhibitors and chemotherapy may provide better survival benefits than the late combination for patients.

7.
JAMA Ophthalmol ; 140(11): 1076-1083, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36173609

ABSTRACT

Importance: Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO. Objective: To evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO. Design, Setting, and Participants: In this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks. Interventions: Participants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks. Main Outcomes and Measures: The primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded. Results: A total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group. Conclusions and Relevance: The results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT02203682.


Subject(s)
Doxycycline , Graves Ophthalmopathy , Humans , Female , Adult , Male , Doxycycline/adverse effects , Graves Ophthalmopathy/drug therapy , Quality of Life , Lactation , Anti-Bacterial Agents/adverse effects , Double-Blind Method
8.
J Org Chem ; 87(18): 12132-12147, 2022 09 16.
Article in English | MEDLINE | ID: mdl-36062305

ABSTRACT

A facile and efficient base-mediated divergent annulation of methyl 2-(cyanomethyl)benzoates and conjugated ynones has been described. A broad range of 1-naphthols and xanthones were formed in moderate to excellent yields. The notable features of this protocol include readily available precursors, broad substrate scope, complete regioselectivity, and substrate-controlled divergent synthesis. The gram-scale preparation and synthetic transformations of the resulting 1-naphthols and xanthones demonstrate their utility.


Subject(s)
Naphthols , Xanthones , Benzoates , Catalysis , Molecular Structure
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(1): 158-163, 2022 Feb.
Article in Chinese | MEDLINE | ID: mdl-35300779

ABSTRACT

The fatty acid desaturase 2 (FADS2) gene encodes delta-6 desaturase (D6D) and is a member of the fatty acid desaturase gene family.D6D is the key enzyme catalyzing the transformation of linoleic acid and α-linolenic acid to long-chain polyunsaturated fatty acid (LC-PUFA).LC-PUFA play a crucial role in regulating the glycolipid metabolism of living organisms.In recent years,the activity of D6D and the single nucleotide polymorphism (SNP) of FADS2 gene have become a hot topic in the research on glycolipid metabolism.This article reviews the role of FADS2 gene in glycolipid metabolism.


Subject(s)
Fatty Acid Desaturases , Glycolipids , Fatty Acid Desaturases/genetics , Fatty Acid Desaturases/metabolism , Glycolipids/metabolism , Humans , Polymorphism, Single Nucleotide
10.
Genomics ; 113(3): 1482-1490, 2021 05.
Article in English | MEDLINE | ID: mdl-33771636

ABSTRACT

Retinal ischemia-reperfusion (I/R) is involved in the pathogenesis of many vision-threatening diseases. circRNAs act as key players in gene regulation and human diseases. However, the global circRNA expression profile in retinal I/R injury has not been fully uncovered. Herein, we established a murine model of retinal I/R injury and performed circRNA microarrays to identify I/R-related circRNAs. 1265 differentially expressed circRNAs were identified between I/R retinas and normal retinas. Notably, the detection of cWDR37 level in aqueous humor could discriminate glaucoma patients from cataract patients (AUC = 0.9367). cWdr37 silencing protected against hypoxic stress- or oxidative stress-induced retinal ganglion cell (RGC) injury. cWdr37 silencing alleviated IR-induced retinal neurodegeneration as shown by increased NeuN staining, reduced retinal reactive gliosis, and decreased retinal apoptosis. Collectively, this study provides a novel insight into the pathogenesis of retinal I/R injury. cWdr37 is a promising target for the diagnosis or treatment of I/R-related ocular diseases.


Subject(s)
Glaucoma , Reperfusion Injury , Animals , Apoptosis , Glaucoma/genetics , Humans , Mice , RNA, Circular/genetics , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Retina
11.
Mol Ther ; 28(10): 2191-2202, 2020 10 07.
Article in English | MEDLINE | ID: mdl-32755566

ABSTRACT

Epigenetic alterations occur in many physiological and pathological processes. N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic mRNAs. However, the role of m6A modification in pathological angiogenesis remains elusive. In this study, we showed that the level of m6A modification was significantly upregulated in endothelial cells and mouse retinas following hypoxic stress, which was caused by increased METTL3 levels. METTL3 silencing or METTL3 overexpression altered endothelial cell viability, proliferation, migration, and tube formation in vitro. METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization. Mechanistically, METTL3 exerted its angiogenic role by regulating Wnt signaling through the m6A modification of target genes (e.g., LRP6 and dishevelled 1 [DVL1]). METTL3 enhanced the translation of LRP6 and DVL1 in an YTH m6A RNA-binding protein 1 (YTHDF1)-dependent manner. Collectively, this study suggests that METTL3-mediated m6A modification is an important hypoxic stress-response mechanism. The targeting of m6A through its writer enzyme METTL3 is a promising strategy for the treatment of angiogenic diseases.


Subject(s)
Adenosine/analogs & derivatives , Epigenesis, Genetic , Gene Expression Regulation , Methyltransferases/metabolism , Neovascularization, Pathologic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Adenosine/metabolism , Animals , Biomarkers , Disease Susceptibility , Gene Silencing , Humans , Hypoxia/complications , Hypoxia/metabolism , Mice , Mice, Knockout , Neovascularization, Pathologic/metabolism , Retinal Diseases/etiology , Retinal Diseases/metabolism , Retinal Diseases/pathology , Wnt Signaling Pathway
12.
Development ; 147(6)2020 03 17.
Article in English | MEDLINE | ID: mdl-32094118

ABSTRACT

The most significant feature of meiosis is the recombination process during prophase I. CXXC finger protein 1 (CXXC1) binds to CpG islands and mediates the deposition of H3K4me3 by the SETD1 complex. CXXC1 is also predicted to recruit H3K4me3-marked regions to the chromosome axis for the generation of double-strand breaks (DSBs) in the prophase of meiosis. Therefore, we deleted Cxxc1 before the onset of meiosis with Stra8-Cre The conditional knockout mice were completely sterile with spermatogenesis arrested at MII. Knockout of Cxxc1 led to a decrease in the H3K4me3 level from the pachytene to the MII stage and caused transcriptional disorder. Many spermatogenesis pathway genes were expressed early leading to abnormal acrosome formation in arrested MII cells. In meiotic prophase, deletion of Cxxc1 caused delayed DSB repair and improper crossover formation in cells at the pachytene stage, and more than half of the diplotene cells exhibited precocious homologous chromosome segregation in both male and female meiosis. Cxxc1 deletion also led to a significant decrease of H3K4me3 enrichment at DMC1-binding sites, which might compromise DSB generation. Taken together, our results show that CXXC1 is essential for proper meiotic crossover formation in mice and suggest that CXXC1-mediated H3K4me3 plays an essential role in meiotic prophase of spermatogenesis and oogenesis.


Subject(s)
Crossing Over, Genetic/physiology , Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , Meiosis/physiology , Trans-Activators/physiology , Animals , Cells, Cultured , Embryo, Mammalian , Female , Male , Meiosis/genetics , Methylation , Mice , Mice, Inbred C57BL , Mice, Knockout , Oogenesis/genetics , Protein Processing, Post-Translational/genetics , Spermatogenesis/genetics , Trans-Activators/genetics
13.
Food Chem Toxicol ; 128: 233-239, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30995513

ABSTRACT

The contributions to hypoglycemic function and gut microbiota regulation by water and ethanol extracts of the microalgae Chlorella pyrenoidosa and Spirulina platensis were determined. An ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis indicated that most of the compounds in the 55% ethanol extracts of C. pyrenoidosa (CP55) and S. platensis (SP55) were polyunsaturated fatty acids. After an 8-week high-fat high-sucrose diet with C. pyrenoidosa and S. platensis supplementation, glucose tolerance was improved, and the composition of the gut microbiota was altered. The diversity of the gut bacterial community was evaluated using 16S rRNA gene pyrosequencing. C. pyrenoidosa supplementation increased the abundance of Ruminococcus, Parasutterella, and Erysipelotrichacea and decreased the abundance of Lactobacillus, Turicibacter, and Blautia; S. platensis supplementation increased the abundance of Oscillibacter, Parasutterella, and Alloprevotella and decreased the abundance of Turicibacter. Moreover, Erysipelotrichacea and Ruminococcus were uniquely increased in C. pyrenoidosa treatment groups. Thus, CP55 and SP55 may be developed as effective natural food materials for preventing diabetes, and Ruminococcus may play a vital role in the treatment of diabetes.


Subject(s)
Chlorella/chemistry , Fatty Acids, Unsaturated/analysis , Hypoglycemic Agents/pharmacology , Spirulina/chemistry , Animals , Chromatography, High Pressure Liquid/methods , Gastrointestinal Microbiome/genetics , Glucose Tolerance Test , Male , Mass Spectrometry/methods , RNA, Ribosomal, 16S/genetics , Rats , Species Specificity
14.
Article in Chinese | MEDLINE | ID: mdl-27255046

ABSTRACT

OBJECTIVE: To explore the dynamic changes of transforming growth factor-α (TGF-α) and transforming growth factor-ß1 (TGF-ß1) of liver cirrhosis induced by multiple pathogenic factors in rats. METHODS: Animals in the cirrhosis group were fed a mixture of maize flour, lard, cholesterol and alcohol plus subcutaneously injection with carbon tetrachloride (CCl4), the CCl4(0.5 ml/100 g · w) was injected at the first day of experiment and the 40% CCl4oil solution (0.3 ml /100 g · w) was injected at an interval of three days. The thirty-six male SD rats were randomly divided into liver cirrhosis group of the 4th, 6th and 8 th week, and normal control group of the 4th, 6th and 8th week. The contents of alanine transferase (ALT), endotoxin, tumor necrosis factor-α (TNF-α) and homocysteine (Hcy) in plasma were evaluated. Histopathological changes of the liver were observed under microscope with the staining of HE. The expressions of TGF-α and TGF-ß1 were analyzed by the method of immunohistochemistry. RESULTS: Compared with the corresponding normal control group, the levels of ALT, endotoxin, TNF-α and Hcy in plasma were gradually significantly increased in liver cirrhosis group of the 4th, 6th and 8th week (P < 0.05); the expression of TGF-α in the liver tissues was significantly increased at the 4th week (P < 0.05); the expression of TGF-ß1 in the liver tissues was gradually significantly increased in every model group (P < 0.05). CONCLUSION: In the formation process of cirrhosis, the expression of TGF-α was increased in liver of cirrhosis group at the 4th week, and later it was suppressed; the expression of TGF-ß1 was continuously increased. The characteristic dynamic changes of TGF-α and TGF-ß1 might be related to sustained endotoxemia, the high level of TNF-α and hyperhomocysteinemia.


Subject(s)
Liver Cirrhosis/metabolism , Transforming Growth Factor alpha/metabolism , Transforming Growth Factor beta1/metabolism , Alanine Transaminase/blood , Animals , Carbon Tetrachloride , Endotoxins/blood , Homocysteine/blood , Male , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolism
15.
World J Gastroenterol ; 22(10): 2949-59, 2016 Mar 14.
Article in English | MEDLINE | ID: mdl-26973391

ABSTRACT

AIM: To evaluate the effect of artesunate (AS) supplementation on bacterial translocation (BT) and gut microbiota in a rat model of liver cirrhosis. METHODS: Fifty-four male Sprague-Dawley rats were randomly divided into a normal control group (N), a liver cirrhosis group (M) and a liver cirrhosis group intervened with AS (MA). Each group was sampled at 4, 6 and 8 wk. Liver cirrhosis was induced by injection of carbon tetrachloride (CCl4), intragastric administration of 10% ethanol, and feeding a high fat diet. Rats in the MA group were intragastrically administered with AS (25 mg/kg body weight, once daily). Injuries of the liver and intestinal mucosa were assessed by hematoxylin-eosin or Masson's trichrome staining. Liver index was calculated as a ratio of the organ weight (g) to body weight (g). The gut microbiota was examined by automated ribosomal intergenic-spacer analysis of fecal DNA. BT was assessed by standard microbiological techniques in the blood, mesenteric lymph nodes (MLNs), liver, spleen, and kidney. RESULTS: Compared to group N, the body weight was reduced significantly in groups M and MA due to the development of liver cirrhosis over the period of 8 wk. The body weight was higher in group MA than in group M. The liver indices were significantly elevated at 4, 6 and 8 wk in groups M and MA compared to group N. AS supplementation partially decreased the liver indices in group MA. Marked histopathologic changes in the liver and small intestinal mucosa in group M were observed, which were alleviated in group MA. Levels of pro-inflammatory interleukin-6 and tumor necrosis factor-α were significantly elevated at 8 wk in ileal homogenates in group M compared to group N, which were decreased after AS supplementation in group MA. The dysbiosis of gut microbiota indicated by the mean diversity (Shannon index) and mean similarity (Sorenson index) was severe as the liver cirrhosis developed, and AS supplementation had an apparent intervention effect on the dysbiosis of gut microbiota at 4 wk. The occurrence of BT was increased in the liver of group M compared to that of group N. AS supplementation reduced BT in group MA at 8 wk. BT also occurred in the MLNs, spleen, and kidney, which was reduced by AS supplementation. BT was not detected in the blood in any group. CONCLUSION: Dysbiosis of gut microbiota, injury of intestinal mucosal barrier and BT occurred as liver cirrhosis progressed, which might enhance inflammation and aggravate liver injury. AS may have other non-antimalarial effects that modulate gut microbiota, inhibit BT and alleviate inflammation, resulting in a reduction in CCl4, alcohol and high fat-caused damages to the liver and intestine.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Artemisinins/pharmacology , Bacteria/drug effects , Bacterial Translocation/drug effects , Dysbiosis , Gastrointestinal Microbiome/drug effects , Intestines/drug effects , Liver Cirrhosis, Experimental/drug therapy , Animals , Artesunate , Bacteria/immunology , Bacteria/metabolism , Carbon Tetrachloride , Cytokines/immunology , Cytokines/metabolism , Disease Progression , Feces/microbiology , Inflammation Mediators/immunology , Inflammation Mediators/metabolism , Intestinal Mucosa/metabolism , Intestines/immunology , Intestines/microbiology , Liver Cirrhosis, Experimental/chemically induced , Liver Cirrhosis, Experimental/immunology , Liver Cirrhosis, Experimental/microbiology , Male , Rats, Sprague-Dawley , Time Factors
16.
Breastfeed Med ; 10(3): 163-7, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25785993

ABSTRACT

OBJECTIVE: This study aimed to assess the association of breastfeeding and maternal hypertension and diabetes in Beijing, China. SUBJECTS AND METHODS: A cross-sectional study was conducted in four urban communities of Beijing, China, with 9,128 parous women 40-81 years of age who had had only one lifetime birth. Each participant completed a detailed survey and accepted blood pressure measurement and blood glucose testing. Moreover, self-reported hypertension and diabetes were confirmed by review of medical records. RESULTS: After the analysis was adjusted for the potential confounders, including age, body mass index (BMI), waist to hip ratio (WHR), working status, educational level, drinking, smoking, family history of hypertension, age of menarche, menopause, oral contraceptive use, age of child-bearing, and postpartum BMI, the odd ratio (OR) of hypertension was 1.18 (95% confidence interval [CI], 1.05-1.32) for women who did not breastfeed, compared with women who did. In addition, the ORs for >0 to 6 months, >6 to 12 months, and >12 months of breastfeeding were 0.87 (95% CI, 0.76-0.99), 0.83 (95% CI, 0.68-1.00), and 0.79 (95% CI, 0.65-0.97), respectively, compared with women who did not breastfeed. With adjustment for age, WHR, working status, educational level, family history of diabetes, and postpartum BMI, women who did not breastfeed increased the risk of diabetes (OR=1.30; 95% CI, 1.11-1.53) compared with women who did. Moreover, women who breastfed for >0 to 6 months (OR=0.81; 95% CI, 0.67-0.98) and >6 to 12 months (OR=0.46; 95% CI, 0.26-0.84) had a lower risk of diabetes, compared with women who did not breastfeed. CONCLUSIONS: Chinese mothers who did not breastfeed were more likely to develop hypertension and diabetes in later life.


Subject(s)
Breast Feeding/statistics & numerical data , Diabetes Mellitus, Type 2/epidemiology , Hypertension/epidemiology , Mothers/statistics & numerical data , Adult , Aged , Blood Pressure , China/epidemiology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/etiology , Female , Glucose Tolerance Test , Health Surveys , Humans , Hypertension/blood , Hypertension/etiology , Middle Aged , Parity , Pregnancy , Prevalence , Surveys and Questionnaires , Time Factors , Women's Health
17.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 30(3): 199-203, 2014 May.
Article in Chinese | MEDLINE | ID: mdl-25244780

ABSTRACT

OBJECTIVE: To explore the mechanism of tanshinol on alleviate the inflammatory injury of lung tissue in rat hepatopulmonary syndrome (HPS). METHODS: SD rats were randomly divided into normal control group (n = 8), hepatopulmonary syndrome (HPS) group (n = 11) and tanshinol intervention group (n = 9). HE staining was used to observe the histopathology changes of pulmonary and hepatic tissues, and to count the number of macrophages in lung tissues. The activity of alanine transferase (ALT) and concentrations of endotoxin, tumor necrosis factor-a (TNF-alpha) and homocystein (Hcy) in plasma were detected. The concentrations of TNF-alpha, nitric oxide (NO) and malondialdehyde (MDA) and the activity of inducible nitric oxide synthase (iNOS) in the lung tissues were measured, respectively. RESULTS: Thickened alveolar septum and increased macrophages were observed in lungs in HPS rat. After administered with tanshinol, the pulmonary pathological changes were alleviated and the number of macrophages in lung tissue was decreased compared with HPS group. The activity of ALT and the concentrations of endotoxin, TNF-alpha and Hcy in plasma ,and TNF-alpha, iNOS, NO and MDA in lung tissue in HPS group were higher than those of normal control group; meanwhile, those tanshinol group were less those that of HPS group. CONCLUSION: Tanshinol may play an important role in delaying the development of HPS through protecting liver or directly antagonizing the effect of intestinal endotoxemia so as to alleviate the inflammatory reaction in lung tissue.


Subject(s)
Caffeic Acids/pharmacology , Hepatopulmonary Syndrome/drug therapy , Alanine Transaminase/metabolism , Animals , Disease Models, Animal , Endotoxins/blood , Hepatopulmonary Syndrome/pathology , Homocysteine/blood , Liver/drug effects , Liver/pathology , Lung/drug effects , Lung/pathology , Macrophages/drug effects , Macrophages/pathology , Male , Malondialdehyde/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/blood
18.
Yao Xue Xue Bao ; 49(5): 644-51, 2014 May.
Article in English | MEDLINE | ID: mdl-25151735

ABSTRACT

In recent studies some urea derivatives have been identified as potent anti-tuberculosis agents by targeting mycobacterial membrane protein large 3 (MmpL3). However, this compound series as exemplified by AU1235 exhibited poor in vitro pharmacokinetic profile. With AU1235 as the lead, we have identified a novel benzimidazole series as potential anti-tuberculosis agents by using scaffold hopping approach. Among these synthesized compounds, 2-aminobenzimidazole derivative 8b showed the potent anti-tuberculosis activity with the MIC value of 0.03 microg x mL(-1). This compound also showed improved metabolic stability compared to AU1235. Our investigation indicated that benzimidazole derivatives are the promising lead for further optimization as anti-tuberculosis agents.


Subject(s)
Antitubercular Agents/pharmacology , Benzimidazoles/pharmacology , Tuberculosis/drug therapy , Benzimidazoles/chemistry , Drug Design , Humans , Structure-Activity Relationship
19.
PLoS One ; 9(7): e102323, 2014.
Article in English | MEDLINE | ID: mdl-25050994

ABSTRACT

OBJECTIVE: This meta-analysis was conducted to evaluate the correlations of a common polymorphism (677C>T) in the methylenetetrahydrofolate reductase (MTHFR) gene with risk of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). METHOD: The following electronic databases were searched without language restrictions: Web of Science (1945∼2013), the Cochrane Library Database (Issue 12, 2013), MEDLINE (1966∼2013), EMBASE (1980∼2013), CINAHL (1982∼2013) and the Chinese Biomedical Database (CBM) (1982∼2013). Meta-analysis was performed using STATA statistical software. Odds ratios (ORs) with their 95% confidence intervals (95%CIs) were calculated. RESULTS: Eight cohort studies met all inclusion criteria and were included in this meta-analysis. A total of 2,292 ESRD patients with CVD were involved in this meta-analysis. Our meta-analysis results revealed that the MTHFR 677C>T polymorphism might increase the risk of CVD in ESRD patients (TT vs. CC: OR = 2.75, 95%CI = 1.35∼5.59, P = 0.005; CT+TT vs. CC: OR = 1.39, 95%CI = 1.09∼1.78, P = 0.008; TT vs. CC+CT: OR = 2.52, 95%CI = 1.25∼5.09, P = 0.010; respectively). Further subgroup analysis by ethnicity suggested that the MTHFR 677C>T polymorphism was associated with an elevated risk for CVD in ESRD patients among Asians (TT vs. CC: OR = 3.38, 95%CI = 1.11∼10.28, P = 0.032; CT+TT vs. CC: OR = 1.44, 95%CI = 1.05∼1.97, P = 0.022; TT vs. CC+CT: OR = 3.15, 95%CI = 1.02∼9.72, P = 0.046; respectively), but not among Africans or Caucasians (all P>0.05). CONCLUSION: Our findings indicate that the MTHFR 677C>T polymorphism may be associated with an elevated risk for CVD in ESRD patients, especially among Asians.


Subject(s)
Cardiovascular Diseases/genetics , Kidney Failure, Chronic/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Case-Control Studies , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Polymorphism, Single Nucleotide , Risk Factors
20.
Biomed Environ Sci ; 27(5): 378-84, 2014 May.
Article in English | MEDLINE | ID: mdl-24827719

ABSTRACT

OBJECTIVE: Calibrated Automated Thrombogram(CAT) is a test to monitor the generation of thrombin. It can be described by four parameters: lag time, peak thrombin, endogenous thrombin potential (ETP) and time to peak (ttPeak). This study aims to determine the normal ranges of CAT parameters in Chinese, and evaluate whether thrombin generation is correlated with the concentration of heparin/low molecular weight heparin. METHODS: Plasma from 120 healthy subjects were collected to determine the normal rangea of CAT parameters in Chinese. Normal plasma pool (NPP, n=25) spiked with different concentrations of heparin or enoxaparin were used to detecte CAT parameters. The overall and age specific normal ranges of CAT parameters were calculated using descriptive statistics method with mean±2SD. The correlation between CAT parameters and age or concentrations of heparin, enoxaparin were analyzed with linear regression model. RESULTS: The normal ranges for lag time, peak thrombin, ETP, ttPeak in the subjects were 3.648±2.465 min, 367.39±151.93 nmol/L, 2277±1030 nmol/L•min and 6.372±4.280 min respectively. Age was linearly correlated with lag time (r=-0.6583, P<0.0001), peak thrombin (r=0.4863, P<0.0001), ETP (r=0.3608, P<0.0014) and ttPeak (r=-0.6313, P<0.0001). The values of ETP/peak ratio were linearly correlated with concentrations of heparin. CONCLUSION: The normal ranges of four CAT parameters for Chinese were determined. CAT parameters are associated with age. ETP/peak ratio could be used to monitor the process of anticoagulation therapy.


Subject(s)
Blood Coagulation Tests/standards , Adolescent , Adult , Aged , Aging/blood , Asian People , China , Female , Healthy Volunteers , Heparin , Humans , Male , Middle Aged , Reference Values , Thrombin/analysis , Young Adult
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