ABSTRACT
We developed and experimentally realized a scheme of optical nonreciprocity (ONR) by using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition Fg = 4 â Fe = 3, we first studied the cavity-transmission property in different coupling field configurations and verified that under the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) showed ONR. The stable ground-state Zeeman coherence for Λ-chains involved in the degenerate two-level system was found to be important in the formation of intracavity EIT. However, different from the three-level atom-cavity system, in the degenerate two-level system, the ONR effect based on intracavity EIT occurred only at a low probe intensity, because the cavity-atom coupling strength was weakened in the counter-propagating probe and coupling field configuration. Furthermore, ONR transmission with a high contrast and linewidth-narrowing was experimentally demonstrated.
ABSTRACT
As global climate change persists, ongoing warming exposes plants, including kiwifruit, to repeated cycles of drought stress and rewatering, necessitating the identification of drought-resistant genotypes for breeding purposes. To better understand the physiological mechanisms underlying drought resistance and recovery in kiwifruit, moderate (40-45% field capacity) and severe (25-30% field capacity) drought stresses were applied, followed by rewatering (80-85% field capacity) to eight kiwifruit rootstocks in this study. We then conducted a multivariate analysis of 20 indices for the assessment of drought resistance and recovery capabilities. Additionally, we identified four principal components, each playing a vital role in coping with diverse water conditions. Three optimal indicator groups were pinpointed, enhancing precision in kiwifruit drought resistance and recovery assessment and simplifying the evaluation system. Finally, MX-1 and HW were identified as representative rootstocks for future research on kiwifruit's responses to moderate and severe drought stresses. This study not only enhances our understanding of the response mechanisms of kiwifruit rootstocks to progressive drought stress and recovery but also provides theoretical guidance for reliable screening of drought-adaptive kiwifruit genotypes.
Subject(s)
Actinidia , Drought Resistance , Actinidia/genetics , Actinidia/physiology , Drought Resistance/genetics , Fruit/genetics , Fruit/physiology , Genotype , Multivariate Analysis , Plant Roots/physiology , Plant Roots/genetics , Stress, Physiological/geneticsABSTRACT
Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling of the pulmonary vasculature and elevated pulmonary arterial pressure, ultimately leading to right heart failure and death. Despite its clinical significance, the precise molecular mechanisms driving PAH pathogenesis warrant confirmation. Compelling evidence indicates that during the development of PAH, pulmonary vascular cells exhibit a preference for energy generation through aerobic glycolysis, known as the "Warburg effect", even in well-oxygenated conditions. This metabolic shift results in imbalanced metabolism, increased proliferation, and severe pulmonary vascular remodeling. Exploring the Warburg effect and its interplay with glycolytic enzymes in the context of PAH has yielded current insights into emerging drug candidates targeting enzymes and intermediates involved in glucose metabolism. This sheds light on both opportunities and challenges in the realm of antiglycolytic therapy for PAH.
Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Pulmonary Arterial Hypertension/metabolism , Familial Primary Pulmonary Hypertension , Glycolysis , Lung/metabolism , Pulmonary Artery/metabolism , Vascular RemodelingABSTRACT
OBJECTIVE: Reviews have shown that mindfulness-based interventions (MBIs) were effective in improving cardiovascular risk factors (CVRFs), but the results were contradictory. This umbrella review aimed to summarize and grade the existing reviews on CVRFs associated with MBIs. METHODS: The protocol of this umbrella review had been registered in PROSPERO (CRD42022356812). PubMed, Web of science, Embase, The Cochrane Library, Scopus, Medline, PsycINFO and CINAHL were searched from database inception to 20 July 2022. The quality of evidence was assessed through GRADE. RESULTS: Twenty-seven reviews with 14,923 participants were included. Overall, 45% of reviews had low heterogeneity (I2 < 25%). For the quality of evidence, 31% were rated very low, 42% were rated low, 17% were rated moderate and 10% were rated high. MBIs significantly improved systolic blood pressure [SMD -5.53 mmHg (95% CI -7.81, -3.25)], diastolic blood pressure [SMD -2.13 mmHg (95% CI -2.97, -1.30)], smoking [Cohen's d 0.42 (95% CI 0.20, 0.64)], glycosylated hemoglobin [MD 0.01 (95% CI -0.43, -0.07)], binge eating behavior [SMD -6.49 (95% CI -10.80, -2.18)], depression [SMD -0.72 (95% CI -1.23, -0.21)] and stress [SMD -0.67 (95% CI -1.00, -0.34)]. CONCLUSIONS: In conclusion, this umbrella review provided evidence for the role of MBIs in the improvement of CVRFs.
Subject(s)
Heart Disease Risk Factors , Mindfulness , Humans , Anxiety/etiology , Blood Pressure , Depression/etiology , Mindfulness/methods , Systematic Reviews as Topic , Meta-Analysis as TopicABSTRACT
BACKGROUND: Plutella xylostella (Linnaeus) is a destructive pest of cruciferous crops due to its strong reproductive capacity and extensive resistance to pesticides. Seminal fluid proteins (SFPs) are the main effective factors that determine the reproductive physiology and behaviour of both sexes. Although an increasing number of SFPs have been identified, the effects of astacins in SFPs on agricultural pests have not yet been reported. Here, we elucidated the mechanisms by which Sast1 (seminal astacin 1) regulates the fertility of Plutella xylostella (L.). RESULTS: PxSast1 was specifically expressed in the testis and accesssory gland. CRISPR/Cas9-induced PxSast1 knockout successfully constructed two homozygous mutant strains. Sast1 impaired the fertility of P. xylostella by separately regulating the reproductive capacity of males and females. Loss of PxSast1, on the one hand, significantly decreased the ability of males to mate and fertilize, mainly manifested as shortened mating duration, reduced mating competitiveness and decreased eupyrene sperm production; on the other hand, it significantly inhibited the expression of chorion genes in females, resulting in oogenesis deficits. Simultaneously, for mated females, the differentially expressed genes in signalling pathways related to oogenesis and chorion formation were significantly enriched after PxSast1 knockout. CONCLUSION: These analyses of the functions of PxSast1 as the regulator of spermatogenesis and oogenesis establish its importance in the fertility process of P. xylostella, as well as its potential as a promising target for genetic regulation-based pest control. © 2024 Society of Chemical Industry.
Subject(s)
Insect Proteins , Moths , Animals , Female , Male , Fertility , Insect Proteins/genetics , Insect Proteins/metabolism , Moths/genetics , Moths/growth & development , Seminal Plasma Proteins/genetics , Seminal Plasma Proteins/metabolismABSTRACT
BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.
Subject(s)
Cardiovascular Diseases , Hypertension, Pulmonary , Humans , Clonal Hematopoiesis , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/genetics , Hematopoiesis/genetics , Cardiovascular Diseases/genetics , MutationABSTRACT
Hepatocellular carcinoma (HCC) is the most widespread histological form of primary liver cancer, and it faces great diagnostic and therapeutic difficulties owing to its tumor diversity. Herein, we aim to establish a unique prognostic molecular subtype (MST) and based on this to find potential therapeutic targets to develop new immunotherapeutic strategies. Using calcium channel molecules expression-based consensus clustering, we screened 371 HCC patients from The Cancer Genome Atlas to screen for possible MSTs. We distinguished core differential gene modules between varying MSTs, and Tumor Immune Dysfunction and Exclusion scores were employed for the reliable assessment of HCC patient immunotherapeutic response rate. Immunohistochemistry and Immunofluorescence staining were used for validation of predicted immunotherapy outcomes and underlying biological mechanisms, respectively. We identified two MSTs with different clinical characteristics and prognoses. Based on the significant differences between the two MSTs, we further identified Follistatin-like 3 (FSTL3) as a potential indicator of immunotherapy resistance and validated this result in our own cohort. Finally, we found that FSTL3 is predominantly expressed in HCC stromal components and that it is a factor in enhancing fibroblast-M2 macrophage signaling crosstalk, the function of which is relevant to the pathogenesis of HCC. The presence of two MSTs associated with the calcium channel phenotype in HCC patients may provide promising directions for overcoming immunotherapy resistance in HCC, and the promotion of FSTL3 expressed in stromal components for HCC hyperfibrosis may be responsible for the poor response rate to immunotherapy in Cluster 2 (C2) patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Calcium Channels , Carcinoma, Hepatocellular/genetics , Cluster Analysis , Immunotherapy , Liver Neoplasms/geneticsABSTRACT
Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, LLGL2 regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of LLGL2 in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved LLGL2 overexpression and knockdown showed that LLGL2 inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells.
ABSTRACT
Pulmonary arterial hypertension (PAH) is a complex and progressive disease characterized by pulmonary arterial remodeling. Despite that current combination therapy has shown improvement in morbidity and mortality, a better deciphering of the underlying pathological mechanisms and novel therapeutic targets is urgently needed to combat PAH. MicroRNA, the critical element in post-transcription mechanisms, mediates cellular functions mainly by tuning downstream target gene expression. Meanwhile, upstream regulators can regulate miRNAs in synthesis, transcription, and function. In vivo and in vitro studies have suggested that miRNAs and their regulators are involved in PAH. However, the miRNA-related regulatory mechanisms governing pulmonary vascular remodeling and right ventricular dysfunction remain elusive. Hence, this review summarized the controversial roles of miRNAs in PAH pathogenesis, focused on different miRNA-upstream regulators, including transcription factors, regulatory networks, and environmental stimuli, and finally proposed the prospects and challenges for the therapeutic application of miRNAs and their regulators in PAH treatment.
Subject(s)
Hypertension, Pulmonary , MicroRNAs , Pulmonary Arterial Hypertension , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Pulmonary Arterial Hypertension/drug therapy , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/metabolism , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/genetics , Lung/pathology , Transcription Factors/metabolism , Vascular Remodeling , Pulmonary ArteryABSTRACT
Several randomized controlled trials (RCTs) have investigated the effects of fermented foods on metabolic outcomes in adult patients suffering from diabetes and prediabetes. However, the results of these RCTs are conflicting. This systematic review and meta-analysis was carried out on data from RCTs to evaluate the effects of fermented foods in patients with diabetes and prediabetes. The PubMed, Web of Science, Embase, the Cochrane Library and Scopus databases were searched up to 21 June, 2022. English-language RCTs of fermented foods consumption were included which gave metabolic outcomes on body composition, glucose control, insulin sensitivity, lipid profile, as well as blood pressure. Eighteen RCTs met the inclusion criteria and 843 participants were included in the final analysis. The pooled results showed a significant reduction of fasting blood glucose (FBG), the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), low density lipid cholesterol (LDL-C) and diastolic blood pressure (DBP) in the intervention group versus the control group. The results of this research showed that fermented foods have the potential to improve some metabolic outcomes, including FBG, HOMA-IR, TC, LDL-C, and DBP in patients with diabetes and prediabetes.
ABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I2 > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214). RESULTS: The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20). CONCLUSIONS: Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution.
Subject(s)
Adenomyosis , Intrauterine Devices, Medicated , Female , Humans , Levonorgestrel/therapeutic use , Adenomyosis/surgery , Adenomyosis/pathology , Dysmenorrhea/therapy , Uterus/pathology , MenstruationABSTRACT
PURPOSE: To explore the utility of CTE in the evaluation of bowel invasion in patients with primary ovarian, fallopian tube, and peritoneal cancer. METHODS: This observational study included 73 patients who received CTE before operation between September 2019 and December 2021. Two radiologists reviewed CTE images, focusing on the sites and depth of bowel involvement. Based on the findings during surgical exploration, we evaluated the diagnostic power, like sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+ LR), and negative likelihood ratio (- LR) of CTE. Additionally, the characteristic images of bowel involvement on CTE corresponding to surgical findings were shown in the study. RESULTS: The rate of macroscopic bowel invasion in this cohort was 49.31% (36/73), of which eight patients had small bowel involvement, 17 patients had colon involvement and 27 patients had sigmoid-rectum involvement. CTE detected bowel invasion in the small intestine with a sensitivity, specificity, PPV, NPV, and accuracy of 87.50%, 92.31%, 58.33%, 98.36%, 91.78%; for colon, the statistics were 58.82%, 96.43%, 83.33%, 88.52%, 87.67% and for sigmoid-rectum 62.96%, 82.61%, 68.00%, 79.17%, 75.34%, respectively. CONCLUSION: CTE appeared a preferable diagnostic power on the small bowel and colon invasion in patients with primary ovarian, fallopian tube, and peritoneal cancer.
Subject(s)
Crohn Disease , Ovarian Neoplasms , Carcinoma, Ovarian Epithelial , Crohn Disease/diagnosis , Female , Humans , Intestine, Small , Ovarian Neoplasms/diagnostic imaging , Sensitivity and Specificity , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND AND OBJECTIVES: Primary fallopian tube cancer (PFTC) shares the same diagnostic and management guidelines with epithelial ovarian cancer (EOC). The LION trail raised concerns regarding the role of systematic pelvic and para-aortic lymphadenectomy during debulking surgery. We aimed to evaluate the significance of lymphadenectomy in PFTC survival. METHODS: This retrospective study analyzed the clinical features and survival of patients with PFTC who underwent primary surgery in our center between January 2013 and October 2020. RESULTS: Sixty-one patients diagnosed with PFTC were included in the study. Twenty-five (41.0%, 25/61) were diagnosed with FIGO (International Federation of Gynecology and Obstetrics) stages I/II and 36 (59.0%, 36/61) were diagnosed with stage III/IV. Twenty-nine (47.5%, 29/61) underwent pelvic lymphadenectomy with or without para-aortic lymphadenectomy, among which 12 (41.4%, 12/29) had lymph node metastasis confirmed by postoperative pathology. The mean progression-free survival was 60.4 months in the lymphadenectomy group and 37.8 months in the no-lymphadenectomy group (p = 0.042, HR 0.374, 95% CI 0.145-0.966). CONCLUSIONS: PFTC is often diagnosed earlier and has a better prognosis than EOC. Most patients with PFTC would benefit from lymphadenectomy. However, the extent to which this association translates to a more diverse population needs to be further identified.
Subject(s)
Fallopian Tube Neoplasms , Ovarian Neoplasms , Fallopian Tube Neoplasms/diagnosis , Fallopian Tube Neoplasms/pathology , Fallopian Tube Neoplasms/surgery , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Retrospective StudiesABSTRACT
Objective: High-intensity focused ultrasound (HIFU) is an innovative non-invasive technology used for adenomyosis. Gonadotropin-releasing hormone agonist (GnRH-a) is a hormone commonly used for adenomyosis. We investigated and assessed the efficacy of HIFU combined with GnRH-a for adenomyosis. Methods: For this systematic review and meta-analysis, we searched Pubmed, Cochrane Library, Web of Science, Embase, CNKI, WanFang, and VIP databases for relevant articles published in Chinese or English that compared HIFU combined with GnRH-a vs. HIFU alone in patients with adenomyosis. The last literature search was completed on January 31, 2021. Two reviewers independently assessed study eligibility and assessed risk of bias. Another two reviewers extracted the data. The RevMan5.3 software was used for the data analysis. Changes in volume of the uterine and adenomyotic lesion were defined as the primary outcomes. The secondary outcomes were visual analog scale (VAS) scores for dysmenorrhea, menstrual volume scores, serum CA125 levels, and recurrence rate. This study is registered with PROSPERO (CRD42021234301). Results: Three hundred and ninety potentially relevant articles were screened. Nine studies with data for 766 patients were finally included. Compared with the HIFU alone group, the HIFU combined with GnRH-a group had a higher rate of uterine volume reduction (MD 7.51, 95% CI 5.84-9.17, p < 0.00001), smaller adenomyotic lesion volume (MD 4.11, 95% CI 2.93-5.30, p < 0.00001), lower VAS score for dysmenorrhea (MD 1.27, 95% CI 0.54-2.01, p = 0.0007) and menstrual volume score (MD 0.88, 95% CI 0.73-1.04, p < 0.00001), and lower CA125 level (SMD 0.31, 95% CI 0.05-0.56, p = 0.02) after the procedure. The recurrence rate in the HIFU combined with GnRH-a group was lower than that in the HIFU alone group (RR 0.28, 95% CI 0.10-0.82, p = 0.02). Conclusions: Compared with HIFU treatment alone, HIFU combined with GnRH-a for the treatment of adenomyosis has greater efficacy in decreasing the volumes of the uterine and adenomyotic lesions and alleviating symptoms. However, since the number of the included studies was too small and most of them were written in Chinese, this conclusion needs to be referenced with caution. And the long-term evidence of its efficacy is still insufficient. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ identifier [CRD42021234].
Subject(s)
Adenomyosis , High-Intensity Focused Ultrasound Ablation , Adenomyosis/surgery , Dysmenorrhea/therapy , Female , Gonadotropin-Releasing Hormone , Humans , Neoplasm Recurrence, LocalABSTRACT
Grafting is a technique that provides a substantial way to enhance nutrient utilization thereby improves plant growth and yield quality. Although it is commonly practised in horticultural crops, the impact of scion-rootstock interaction on nutrient distribution is still unclear. Here, 'Newhall' navel orange plants grafted on Trifoliate orange (T) as the original rootstock were inarched with trifoliate orange (N/Tt combination) or carrizo citrange (N/Tc combination) rootstock seedlings. The experimental plants were treated with isotope 10B solution for 7 weeks to investigate the effect of different inarched rootstocks on B distribution and translocation by using a two-root system. From this study, the original rootstock played a more dominant role in B distribution to scion tissues than the inarching rootstock either in N/Tt or N/Tc combination. From inarched combinations, the carrizo citrange in the N/Tc combination had a higher ability to distribute B to new leaves, new twigs and old twigs than trifoliate orange in the N/Tt combination. However, the original rootstock of N/Tt distributed more B to scion tissues than N/Tc and the B concentration in old leaves and new leaves of N/Tt plants was significantly higher than that of N/Tc plants. These results suggest that scion B status is influenced by the B distribution of two inarching rootstocks in an inarching plant, as well as the affinity between the inarching rootstock and grafted plant. In addition, by either adding 10B to the inarching rootstock or original rootstock, we could detect 10B in the other rootstock root in both N/Tt and N/Tc combinations. The results further suggest that B can translocate from rootstock to leaves and then, re-translocate from scion to rootstock through the cycling of B transportation.
Subject(s)
Citrus sinensis , Citrus , Boron , Plant Leaves , Plant RootsABSTRACT
Many long noncoding RNAs (lncRNAs) have been annotated, but their functions remain unknown. The authors found a novel lnc-APUE (lncRNA accelerating proliferation by upregulating E2F1) that is upregulated in different cancer types, including hepatocellular carcinoma (HCC), and high lnc-APUE level is associated with short recurrence-free survival (RFS) of HCC patients. Gain- and loss-of-function analyses showed that lnc-APUE accelerated G1/S transition and tumor cell growth in vitro and allows hepatoma xenografts to grow faster in vivo. Mechanistically, lnc-APUE binds to miR-20b and relieves its repression on E2F1 expression, resulting in increased E2F1 level and accelerated G1/S phase transition and cell proliferation. Consistently, lnc-APUE level is positively associated with the expression of E2F1 and its downstream target genes in HCC tissues. Further investigations disclose that hepatocyte nuclear factor 4 alpha (HNF4α) binds to the lnc-APUE promoter, represses lnc-APUE transcription, then diminishes E2F1 expression and cell proliferation. HNF4α expression is reduced in HCC tissues and low HNF4α level is correlated with high lnc-APUE expression. Collectively, a HNF4α/lnc-APUE/miR-20b/E2F1 axis in which HNF4α represses lnc-APUE expression and keeps E2F1 at a low level is identified. In tumor cells, HNF4α downregulation leads to lnc-APUE upregulation, which prevents the inhibition of miR-20b on E2F1 expression and thereby promotes cell cycle progression and tumor growth.
Subject(s)
Carcinoma, Hepatocellular/genetics , E2F1 Transcription Factor/genetics , Hepatocyte Nuclear Factor 4/genetics , Liver Neoplasms/genetics , RNA, Long Noncoding/genetics , Up-Regulation/genetics , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Disease Models, Animal , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Mice , Mice, Inbred NOD , MicroRNAs/genetics , S Phase/geneticsABSTRACT
Objective: To investigate the effects of exogenous NaHS on myelin basic protein (MBP) and learning and memory of hippocampal neurons in mice with spinocerebellar ataxia type 3 (SCA3) and its therapeutic significance.Methods: Twelve male normal mice were randomly selected as normal control group (NC Group), and 48 SCA3 mice were randomly selected as SCA3 model group (M Group), low dose group (NL Group, 10 µmol/kg), medium dose group (NM Group, 50µmol/kg) and high dose group (NH Group, 100 µmol/kg), 12 rats in each group. The drug treated groups were injected with NaHS intraperitoneally once a day for 4 weeks. The changes of learning and memory ability of SCA3 mice before and after the intervention of different doses of NaHS were determined by Morris water maze, the content of hydrogen sulfide (H2S) in hippocampus was measured by spectrophotometry, the expression of MBP was detected by immunohistochemistry, and the morphological changes of neuron myelin sheath were observed by electron microscope. Results: Compared with the control group, the learning and memory ability of SCA3 mice was decreased significantly (Pï¼0.05), and the content of H2S in hippocampus was decreased (Pï¼0.05). After different doses of exogenous NaHS treatment, the learning and memory ability was improved in different degrees (Pï¼0.05), and the contents of H2S and MBP in hippocampus of SCA3 mice were also improved in different degrees (Pï¼0.05). Conclusion: Exogenous NaHS may increase the contents of H2S and MBP in the hippocampus of SCA3 mice, which may have a protective effect on the neurons, and then improve the learning and memory ability of SCA3 mice, and provide a new idea for the treatment of SCA3.
Subject(s)
Hydrogen Sulfide , Learning , Memory , Spinocerebellar Ataxias , Sulfides , Animals , Hippocampus/drug effects , Learning/drug effects , Male , Memory/drug effects , Mice , Myelin Basic Protein , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Rats , Spinocerebellar Ataxias/drug therapy , Sulfides/pharmacology , Sulfides/therapeutic useABSTRACT
The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions. Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme. Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC. The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients. Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells. The levels of O-linked ß-N-acetylglucosamine (O-GlcNAc) and intranuclear ß-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT). These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.
Subject(s)
Cell Nucleus/metabolism , Epithelial-Mesenchymal Transition , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/metabolism , Hexosamines/biosynthesis , Neoplasms, Cystic, Mucinous, and Serous/enzymology , Ovarian Neoplasms/enzymology , beta Catenin/metabolism , Active Transport, Cell Nucleus , Cell Line, Tumor , Cell Movement , Cell Nucleus/genetics , Cell Nucleus/pathology , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/genetics , Glycosylation , Humans , Middle Aged , Neoplasm Invasiveness , Neoplasms, Cystic, Mucinous, and Serous/genetics , Neoplasms, Cystic, Mucinous, and Serous/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Signal TransductionABSTRACT
The ALPL gene is linked to hypophosphatasia, a rare genetic disease. Owing to the inverse relationships between ALPL expression and both the International Federation of Gynecology and Obstetrics (FIGO) stages and histological grades assigned to patients with serous ovarian cancer (SOC), this study was designed to explore the role and possible mechanisms of ALPL in cell motility of high grade SOC (HGSOC). The effects of ALPL overexpression on migration and invasion were detected in HGSOC cell lines SKOV3 and HEY. Gene ontology analysis for differential genes with ALPL overexpression identified several biological processes, including EMT, correlated with cell motility. Genes potentially implicated in EMT and associated with ALPL were screened using The Cancer Genome Atlas (TCGA) database. The WNT receptor Frizzled2 (FZD2) was identified and its role in HGSOC cell motility and survival was investigated. It was found that forced expression of ALPL could inhibit migration, invasion, and EMT in HGSOC cells. It also reduced the expression of FZD2 and its ligand WNT5A, accompanied by suppressed expression of their downstream target phosphorylated-STAT3 (pSTAT3). These effects were initiated via the FZD2 knockdown using siRNA and reversed by recombinant WNT5A protein. The relationship between FZD2 expression and poor HGSOC patient survival was also investigated. This data supports that ALPL might restrict the function of WNT5A-FZD2-STAT3 axis, a non-canonical WNT pathway for promoting EMT progression, which results in attenuated migration and invasion in HGSOC cells and improves survival in patients with SOC.
Subject(s)
Alkaline Phosphatase/metabolism , Cystadenocarcinoma, Serous/pathology , Ovarian Neoplasms/pathology , Wnt Signaling Pathway , Cell Line, Tumor , Cell Movement , Cystadenocarcinoma, Serous/metabolism , Epithelial-Mesenchymal Transition , Female , Humans , Neoplasm Invasiveness/pathology , Ovarian Neoplasms/metabolismABSTRACT
Bottle aging is the final stage before wines are drunk, and is considered as a maturation time when many chemical changes occur. To get a better understanding of the evolution of wines' flavor profile, the flavor compounds (phenolic and volatile compounds), dissolved oxygen (DO), and flavor characters (OAVs and chromatic parameters) of rosé and dry white wines bottled with different closures were determined after 18 months' bottle aging. The results showed the main phenolic change trends of rosé wines were decreasing while the trends of white wines were increasing, which could be the reason for their unique DO changing behaviors. Volatile compounds could be clustered into fluctuating, increasing, and decreasing groups using k-means algorithm. Most volatile compounds, especially some long-chain aliphatic acid esters (octanoates and decanoates), exhibited a lower decrease rate in rosé wines sealed with natural corks and white wines with screw caps. After 18 months of bottle aging, wines treated with natural corks and their alternatives could be distinguished into two groups based on flavor compounds via PLS-DA. As for flavor characters, the total intensity of aroma declined obviously compared with their initial counterparts. Rosé wines exhibit visual difference in color, whereas such a phenomenon was not observed in white wines.