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1.
Biol Reprod ; 110(1): 48-62, 2024 Jan 13.
Article in English | MEDLINE | ID: mdl-37812443

ABSTRACT

Genomic integrity is critical for sexual reproduction, ensuring correct transmission of parental genetic information to the descendant. To preserve genomic integrity, germ cells have evolved multiple DNA repair mechanisms, together termed as DNA damage response. The RNA N6-methyladenosine is the most abundant mRNA modification in eukaryotic cells, which plays important roles in DNA damage response, and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) is a well-acknowledged N6-methyladenosine reader protein regulating the mRNA decay and stress response. Despite this, the correlation between YTHDF2 and DNA damage response in germ cells, if any, remains enigmatic. Here, by employing a Ythdf2-conditional knockout mouse model as well as a Ythdf2-null GC-1 mouse spermatogonial cell line, we explored the role and the underlying mechanism for YTHDF2 in spermatogonial DNA damage response. We identified that, despite no evident testicular morphological abnormalities under the normal circumstance, conditional mutation of Ythdf2 in adult male mice sensitized germ cells, including spermatogonia, to etoposide-induced DNA damage. Consistently, Ythdf2-KO GC-1 cells displayed increased sensitivity and apoptosis in response to DNA damage, accompanied by the decreased SET domain bifurcated 1 (SETDB1, a histone methyltransferase) and H3K9me3 levels. The Setdb1 knockdown in GC-1 cells generated a similar phenotype, but its overexpression in Ythdf2-null GC-1 cells alleviated the sensitivity and apoptosis in response to DNA damage. Taken together, these results demonstrate that the N6-methyladenosine reader YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia, which provides novel insights into the mechanisms underlying spermatogonial genome integrity maintenance and therefore contributes to safe reproduction.


Subject(s)
Acetates , Phenols , RNA-Binding Proteins , Spermatogonia , Animals , Male , Mice , DNA Damage , DNA Repair , Histone Methyltransferases/genetics , Histone Methyltransferases/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Spermatogonia/metabolism , Transcription Factors/genetics
2.
J Clin Gastroenterol ; 58(1): 31-38, 2024 01 01.
Article in English | MEDLINE | ID: mdl-36730560

ABSTRACT

GOALS: A combination of multiple tests was introduced to noninvasively investigate the differences in pathophysiologies among functional dyspepsia (FD) subgroups, including postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlap. BACKGROUND: It has not been extensively evaluated whether different pathophysiologies are involved in FD subgroups. STUDY: This multicenter study included 364 FD patients fulfilling Rome IV criteria and 47 healthy controls. A combined noninvasive gastric and autonomic function test was performed: The electrogastrogram and electrocardiogram were recorded simultaneously in the fasting state and after a drink test. Symptoms after drinking were recorded using visual analog scale. RESULTS: (1) Compared with HC, FD patients showed a decreased maximum tolerable volume (MTV) ( P <0.01) and percentage of normal gastric slow waves [normal gastric slow waves (%NSW)] ( P <0.01), and increased postdrinking symptoms, anxiety ( P <0.01), and depression ( P <0.01). The drink reduced %NSW in both FD patients and HC; however, the effect was more potent in patients. (2) The PDS and overlap groups displayed a reduced MTV ( P <0.05). The overlap group exhibited a higher symptom score at 30 minutes after drinking, and higher anxiety and depression scores, and a higher sympathovagal ratio than the EPS ( P <0.05 for all) and PDS ( P <0.01 for all). (3) In the PDS subgroup, the MTV, postprandial sympathovagal ratio, and depression were associated with the overall dyspepsia symptom scale (DSS, P =0.034, 0.021, 0.043, respectively). No significant associations were found in the other 2 subgroups. CONCLUSIONS: The combination of multiple tests can detect pathophysiological abnormities in FD patients. Overall, patients with overlap symptoms display more severe pathophysiologies.


Subject(s)
Dyspepsia , Gastritis , Humans , Abdominal Pain/etiology , Abdominal Pain/diagnosis , Gastritis/complications , Postprandial Period/physiology
3.
Surg Endosc ; 38(5): 2444-2453, 2024 May.
Article in English | MEDLINE | ID: mdl-38453750

ABSTRACT

BACKGROUND: Peroral endoscopic myotomy (POEM) has emerged as a widely accepted treatment for achalasia, with limited studies for over 2 years. Additionally, traditional measurements of achalasia after POEM have deficiencies. The study aimed to analyze the long-term outcomes of POEM under different criteria. METHODS: Patients with achalasia who received POEM between November 2012 and March 2021 were recruited. Patients and characteristics were shown, and risk factors related to two novel definitions of recurrence, symptomatic reflux, and reflux esophagitis were analyzed. RESULTS: Three hundred and twenty-one patients were included. At a median follow-up of 52 months, twenty-three failures happened (7.17%) under the modified criterion, and forty-seven failures occurred (14.64%) under the normal standard. Hospitalization (P = 0.027) and esophageal myotomy length (P = 0.039) were significantly associated with long-term efficacy under the modified and normal criteria, respectively. Fifty-two patients (16.20%) reported reflux symptoms and endoscopy performed in 88 patients revealed reflux esophagitis in 22 cases (25.00%). There were no predictors in the analysis of symptomatic reflux and gender (P = 0.010), LESP (P = 0.013), IRP (P = 0.015), and the esophageal myotomy length (P = 0.032) were statistically related to reflux esophagitis. CONCLUSION: POEM is an extremely safe and effective treatment for achalasia with long-term follow-up. Shorter hospitalization and shorter esophageal myotomy length may decrease the incidence of recurrence under the modified and normal criteria, respectively. Long-term outcomes of POEM are unpredictable. No risk factors were related to symptomatic reflux, and male patients with low preoperative LESP and IRP needed relatively shorter esophageal myotomy to prevent reflux esophagitis.


Subject(s)
Esophageal Achalasia , Humans , Esophageal Achalasia/surgery , Male , Female , Middle Aged , Adult , Treatment Outcome , Myotomy/methods , Natural Orifice Endoscopic Surgery/methods , Recurrence , Aged , Follow-Up Studies , Esophagoscopy/methods , Retrospective Studies , Young Adult , Adolescent , Esophagitis, Peptic/etiology , Esophagitis, Peptic/prevention & control , Risk Factors
4.
Luminescence ; 39(4): e4729, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38548706

ABSTRACT

To further explore the relationship between aryl substituents and mechanofluorochromic (MFC) behaviors, four salicylaldimine-based difluoroboron complexes (ts-Ph BF2, ts-Ph-NA BF2, ts-2NA BF2, and ts-triphenylamine [TPA] BF2), including aromatic substituents with different steric hindrance effects, were designed and successfully synthesized. Four complexes with twisted molecular conformation displayed intramolecular charge transfer and aggregation-induced emission properties. Under external mechanical stimuli, the as-synthesized powders of ts-Ph BF2, ts-Ph-NA BF2, and ts-TPA BF2 exhibited redshift fluorescence emission behaviors, and ts-Ph BF2 and ts-TPA BF2 could be recovered to original shifts by fuming, but ts-Ph-NA BF2 displayed irreversible switching. ts-2NA BF2 had no change during the grinding and fuming processes. The results indicated that the MFC behaviors could be attributed to the phase transformation between the well-defined crystalline and disordered amorphous states by X-ray diffraction measurement. Further research illustrated that ts-TPA BF2 with the most significant MFC phenomenon could be applied in data security protection in ink-free rewritable paper.


Subject(s)
Computer Security , X-Ray Diffraction
5.
Opt Lett ; 48(9): 2457-2460, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37126297

ABSTRACT

A Ga hybridization strategy is proposed for simultaneously enhancing the near-infrared activity and extending the bandwidth of Bi-activated photonic glass. Systematic studies on the near-infrared optical responses of Ga/Bi and Al/Bi co-doped silica glasses are performed. It is interesting to note that Ga/Bi co-doped glasses have a similar near-infrared emission center to Al/Bi co-doped glass, while the former is more effective in improving near-infrared activity. The different luminescence mechanisms of Ga/Bi and Al/Bi co-doped silica glasses are elucidated, and the corresponding microstructure-optical response relationship is discussed. In addition, the Ga/Bi co-doped silica optical fiber is successfully prepared, and the principal fiber amplifier device is fabricated. Furthermore, amplified spontaneous emission and broadband on-off gain are realized. The results suggest that Ga-hybridized Bi-activated photonic glass is a promising gain material for broadband fiber amplifiers.

6.
BMC Cancer ; 23(1): 912, 2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37770853

ABSTRACT

Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored.Firstly, we assessed cell viability, proliferation, invasion, and migration using three cell lines (HuCCT-1, QBC399, and RBE) to explore the biological characteristics of ROR1-AS1 in CCA. Secondly, to determine the in vivo effect of ROR1-AS1 on tumor growth, ROR1-AS1 knockdown (KD) HuCCT-1 cells were subcutaneously injected into nude mice to evaluate tumor growth. Finally, we conducted a bioinformatic analysis to confirm the role of ROR1-AS1 in the prognosis and immunity of CCA.In this study, we found that lncRNA ROR1-AS1 was increased in CCA samples and patients with higher ROR1-AS1 expression had a shorter overall survival period. siRNA-mediated KD of ROR1-AS1 significantly reduced cell proliferation and inhibited the migration of CCA cells. In addition, ROR1-AS1 KD HuCCT-1 cells injected into nude mice grew slower than normal CCA cells.In summary, our results show that ROR1-AS1 can promote CCA progression and might serve as a new target for diagnosis and treatment of CCA.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , MicroRNAs , RNA, Long Noncoding , Animals , Mice , Humans , Mice, Nude , Cell Line, Tumor , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Movement/genetics , MicroRNAs/genetics , Neoplastic Processes , Cholangiocarcinoma/pathology , Cell Proliferation/genetics , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Gene Expression Regulation, Neoplastic , Receptor Tyrosine Kinase-like Orphan Receptors/genetics , Receptor Tyrosine Kinase-like Orphan Receptors/metabolism
7.
Immunopharmacol Immunotoxicol ; 45(6): 682-691, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37417915

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has a high fatality rate and poses a great threat to human health. Astragaloside IV (AS-IV) is proven to attenuate cigarette smoke (CS)-induced pulmonary inflammation, based on which this research focuses on the mechanism of AS-IV in COPD. METHODS: To evaluate the effects of AS-IV, CD4+ T cells received different concentrations of AS-IV. CD4+ T cell viability, T helper 17 (Th17)/regulatory T (Treg) markers and CXCR4 expressions in CD4+ T cells or spleen/lung tissues were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, quantitative real-time polymerase chain reaction and Western blot. The proportions of Treg and Th17 cells were assessed by flow cytometry. Enzyme-linked immune sorbent assay was employed to determine cytokine contents in serum and lung tissues. RESULTS: AS-IV with concentration exceeding 40 µM inhibited CD4+ T cell viability. In vitro, AS-IV suppressed the expressions of CXCR4, retinoid-related orphan receptor γt (RORγt), and interleukin (IL)-17A as well as Th17 cells but promoted the expressions of forkhead box p3 (Foxp3) and IL-10 as well as Treg cells, while CXCR4 overexpression reversed the effects of AS-IV. In vivo, AS-IV alleviated COPD, and CS-induced Th17/Treg imbalance in mice and reduced CS-induced down-regulation of IL-10 in serum and lung tissues and Foxp3 and up-regulation of IL-1ß, tumor necrosis factor alpha (TNF-α), IL-6, and IL-17A in serum and lung tissues and RORγt. AS-IV mitigated CS-induced CXCR4 up-regulation. Above effects of AS-IV on mice were offset by CXCR4 overexpression. CONCLUSIONS: AS-IV restores Th17/Treg balance via impeding CXCR4 to ameliorate COPD.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Receptors, CXCR4 , Saponins , T-Lymphocytes, Regulatory , Th17 Cells , Male , Animals , Mice , Mice, Inbred ICR , Receptors, CXCR4/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/immunology , Saponins/pharmacology , Triterpenes/pharmacology , Cytokines/metabolism , Spleen/cytology , Lung/cytology
8.
Nat Chem Biol ; 16(11): 1261-1268, 2020 11.
Article in English | MEDLINE | ID: mdl-32895497

ABSTRACT

Dynamic regulation is a promising strategy for fine-tuning metabolic fluxes in microbial cell factories. However, few of these synthetic regulatory systems have been developed for central carbon metabolites. Here we created a set of programmable and bifunctional pyruvate-responsive genetic circuits for dynamic dual control (activation and inhibition) of central metabolism in Bacillus subtilis. We used these genetic circuits to design a feedback loop control system that relies on the intracellular concentration of pyruvate to fine-tune the target metabolic modules, leading to the glucaric acid titer increasing from 207 to 527 mg l-1. The designed logic gate-based circuits were enabled by the characterization of a new antisense transcription mechanism in B. subtilis. In addition, a further increase to 802 mg l-1 was achieved by blocking the formation of by-products. Here, the constructed pyruvate-responsive genetic circuits are presented as effective tools for the dynamic control of central metabolism of microbial cell factories.


Subject(s)
Bacterial Proteins/genetics , Gene Regulatory Networks/drug effects , Pyruvic Acid/metabolism , Amino Acid Sequence , Bacillus subtilis/genetics , Bacterial Proteins/metabolism , Escherichia coli , Gene Expression Regulation, Bacterial , Genomic Library , Glucaric Acid/metabolism , Glucose/metabolism , Histidine/chemistry , Inositol/metabolism , Logic , Metabolic Engineering/methods , Metabolome/genetics , Models, Genetic , Oligopeptides/chemistry , Transcription Factors , Transcription, Genetic
9.
Gastric Cancer ; 25(5): 929-942, 2022 09.
Article in English | MEDLINE | ID: mdl-35752993

ABSTRACT

OBJECTIVE: Endoscopic resection (ER) is an effective treatment method for gastric submucosal tumors (G-SMTs), but endoscopic resection failure requires emergency surgery. The purpose of this study was to assess potential risk factors for endoscopic resection failure. METHODS: A total of 1041 patients with G-SMT undergoing endoscopic resection were enrolled. Twenty-five patients in whom endoscopic resection failed, requiring a transition to surgery midway through the operation, were included in the failed group, and 1016 patients who received successful endoscopic resection were included in the successful endoscopic resection group. Baseline and lesion characteristics were recorded, and the differences in tumor characteristics and risk factors for resection failure of G-SMT were analyzed. Sensitivity analysis was performed to detect the stability of the indicator. RESULTS: Of the 1041cases included, there were 25 cases (2.4%) of failed endoscopic resection. Binary logistic analysis showed that the independent risk factors included tumors originating from deep muscularis propria(OR = 14.42, 95% CI 4.47-46.52), size > 3 cm (OR = 7.75, 95% CI 2.64-22.70), exophytic growth pattern (OR = 4.98, 95% CI 1.62-15.29), endoscopist with less experience (OR = 5.99, 95% CI 1.07-12.19), and irregular borders (OR = 4.13, 95% CI 1.40-12.19). The stable risk factors were tumors size, tumor origin and growth pattern according to sensitivity analysis. CONCLUSIONS: Tumors originating from the deep muscularis propria, tumor size > 3 cm, endoscopists with less experience, an exophytic growth pattern, and irregular boundaries were found to be independent risk factors for endoscopic resection failure. To reduce the risk of endoscopic resection failure, physicians should carefully evaluate G-SMT characteristics preoperative.


Subject(s)
Endoscopic Mucosal Resection , Stomach Neoplasms , Case-Control Studies , Endoscopic Mucosal Resection/methods , Gastric Mucosa/pathology , Gastric Mucosa/surgery , Gastroscopy/methods , Humans , Retrospective Studies , Risk Factors , Stomach Neoplasms/pathology , Treatment Outcome
10.
J Biol Chem ; 295(32): 10885-10900, 2020 08 07.
Article in English | MEDLINE | ID: mdl-32487749

ABSTRACT

tRNA-derived small RNAs (tsRNAs) from spermatozoa could act as acquired epigenetic factors and contribute to offspring phenotypes. However, the roles of specific tsRNAs in early embryo development remain to be elucidated. Here, using pigs as a research model, we probed the tsRNA dynamics during spermatogenesis and sperm maturation and demonstrated the delivery of tsRNAs from semen-derived exosomes to spermatozoa. By microinjection of antisense sequences into in vitro fertilized oocytes and subsequent single-cell RNA-seq of embryos, we identified a specific functional tsRNA group (termed here Gln-TTGs) that participate in the early cleavage of porcine preimplantation embryos, probably by regulating cell cycle-associated genes and retrotransposons. We conclude that specific tsRNAs present in mature spermatozoa play significant roles in preimplantation embryo development.


Subject(s)
Blastocyst , Cell Division , RNA, Transfer, Gln/physiology , RNA/metabolism , Spermatozoa/metabolism , Animals , Embryonic Development , Female , Male , Microinjections , Pregnancy , Sperm Maturation , Spermatogenesis , Swine
11.
Small ; 17(34): e2007442, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34278712

ABSTRACT

Detrimental lithium polysulfide (LiPS) shuttle effects and sluggish electrochemical conversion kinetics in lithium-sulfur (Li-S) batteries severely hinder their practical application. Separator modification has been extensively investigated as an effective strategy to address above issues. Nevertheless, in the case of functional separators, how to effectively block the LiPSs from diffusion while enabling the rapid Li ion transport remains a challenge. Herein, by using an "oxidation-etching" method, MXene membranes are presented with controllable in-plane pores as interlayer to regulate Li ion transportation and LiPS immobilization. Porous MXene membranes with optimized pore density and size can simultaneously anchor LiPS and ensure fast Li ion diffusion. Consequently, even with pure sulfur cathode, the improved Li-S batteries deliver excellent rate performance up to 2 C with a reversible capacity of 677.6 mAh g-1 and long-term cyclability over 500 cycles at 1 C with a low capacity decay of 0.07% per cycle. This work sheds new insights into the design of high-performance interlayers with manipulated nanochannels and tailored surface chemistry to regulate LiPSs trapping and Li ion diffusion in Li-S batteries.

12.
Cancer Control ; 28: 10732748211063955, 2021.
Article in English | MEDLINE | ID: mdl-34913741

ABSTRACT

BACKGROUND: The number of patients diagnosed with T1 stage adenocarcinoma of esophagogastric junction (AEGJ) has been increasing. This study was conducted to investigate the effect of different treatment options (surgery, chemoradiation, and surgery+chemoradiation) on long-term survival in patients with T1-stage AEGJ. METHODS: We searched the Surveillance, Epidemiology, and End Results (SEER) database to identify the records of patients with T1-stage AEGJ between 2010 and 2018. Patient demographics and cancer parameters were compared among the three groups. The Kaplan-Meier method and Cox proportional hazard modeling were used to compare long-term survival. RESULTS: Data from 925 T1 stage AEGJ patients (surgery: n=516, surgery+chemoradiation: n=206, chemoradiation: n=203) were collected. We found that the OS and CSS rates of three treatment options had significant difference. Besides, positive nodal status also showed lower OS and CSS rat. Multivariate Cox regression analysis showed that surgery group has much lower risk of death compared with chemoradiation group and similar risk of death compared with surgery+chemoradiation group. Subgroup analysis suggested that in patients with N1-N3 status had higher OS and CSS rates in surgery+chemoradiation group. CONCLUSION: Using SEER data, we identified a significant survival advantage with the use of surgery compared to chemoradiation in patients with T1-stage AEGJ while the long-term survival of patients after surgery+chemoradiation group was not significantly different and low risk of death in positive nodal status.


Subject(s)
Adenocarcinoma/mortality , Chemoradiotherapy/mortality , Esophageal Neoplasms/mortality , Esophagogastric Junction/surgery , Adenocarcinoma/therapy , Aged , Combined Modality Therapy , Esophageal Neoplasms/therapy , Esophagogastric Junction/pathology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Proportional Hazards Models , Retrospective Studies , SEER Program , Treatment Outcome
13.
Appl Opt ; 60(18): 5345-5353, 2021 Jun 20.
Article in English | MEDLINE | ID: mdl-34263771

ABSTRACT

In this paper, a new, to the best of our knowledge, scheme is proposed to mitigate the atmospheric turbulence effect in coherent free-space optical (FSO) communications with 8-quadrature amplitude modulation by employing amplitude compensation and phase recovery. The amplitude compensation and phase recovery algorithm in the scheme can significantly improve system performance without acquiring instantaneous channel state information or probability density function of a turbulence model. Numerical studies show that the bit error rate of the proposed scheme is four orders of magnitude lower than that of the system without any algorithm over a lognormal turbulence channel with normalized standard deviation of irradiance σ=0.25 and phase noise with normalized variance σϕ2=0.07, when the frequency offset fo=20MHz, combined linewidth Δf=10kHz, and average signal-to-noise ratio γ=20dB. Experiments are also carried out to investigate the performance of the scheme, and the results prove its superiority. Hence, this scheme can contribute to practical realization of the FSO system.

14.
Res Sports Med ; 29(2): 155-169, 2021.
Article in English | MEDLINE | ID: mdl-32491924

ABSTRACT

This study determined the acute changes in kinematics and kinetics when an additional load equivalent to 5% body mass was attached to the torso during change of direction (COD). In this within-subject repeated measures study, 14 male soccer players (age: 18.29 ± 0.32 years) volunteered to participate. Subjects performed COD under two conditions in randomized order: (1) no WR, and (2) with WR. No significant differences between the loaded and unloaded conditions in actual COD angle, approach speed, braking time, propulsive time, contact time, COD completion time (all p > 0.05, ES = 0.05-0.11), and all measured kinematic parameters (all p > 0.05, ES = 0-0.18). Nonetheless, ankle plantar/dorsi flexion ROM had possibly small increase in the loaded condition (ES = 0.24). Kinetics analysis has shown that the loaded condition was likely to have small increase in relative peak vertical propulsive ground reaction force (GRF, p = 0.11, ES = 0.41), and possible small increases in relative peak braking GRF (vertical: p = 0.21, ES = 0.42; total: p = 0.22, ES = 0.38), relative peak total propulsive GRF (p = 0.24, ES = 0.26), and relative braking impulse (horizontal, vertical, and total; p = 0.27-0.41, ES = 0.26-0.28). WR did not significantly change the acute movement techniques, meanwhile induced small increases in important kinetic stimuli for potential adaptation in COD.


Subject(s)
Motor Skills/physiology , Resistance Training/instrumentation , Soccer/physiology , Adolescent , Ankle/physiology , Athletic Performance/physiology , Biomechanical Phenomena , Humans , Kinetics , Male , Range of Motion, Articular , Resistance Training/methods , Time and Motion Studies , Weight-Bearing
15.
J Biol Chem ; 294(49): 18714-18725, 2019 12 06.
Article in English | MEDLINE | ID: mdl-31662436

ABSTRACT

DNA methylation and histone modifications critically regulate the expression of many genes and repeat regions during spermatogenesis. However, the molecular details of these processes in male germ cells remain to be addressed. Here, using isolated murine sperm cells, ultra-low-input native ChIP-Seq (ULI-NChIP-Seq), and whole genome bisulfite sequencing (WGBS), we investigated genome-wide DNA methylation patterns and histone 3 Lys-9 trimethylation (H3K9me3) modifications during mouse spermatogenesis. We found that DNA methylation and H3K9me3 have distinct sequence preferences and dynamics in promoters and repeat elements during spermatogenesis. H3K9me3 modifications in histones at gene promoters were highly enriched in round spermatids. H3K9me3 modification on long terminal repeats (LTRs) and long interspersed nuclear elements (LINEs) was involved in silencing active transcription from these regions in conjunction with reestablishment of DNA methylation. Furthermore, H3K9me3 remodeling on the X chromosome was involved in meiotic sex chromosome inactivation and in partial transcriptional reactivation of sex chromosomes in spermatids. Our findings also revealed the DNA methylation patterns and H3K9me3 modification profiles of paternal and maternal germline imprinting control regions (gICRs) during spermatogenesis. Taken together, our results provide a genome-wide map of H3K9me3 modifications during mouse spermatogenesis that may be helpful for understanding male reproductive disorders.


Subject(s)
DNA Methylation/physiology , Histones/metabolism , Spermatogenesis/physiology , Animals , DNA Methylation/genetics , Epigenomics , Male , Mice , Protein Processing, Post-Translational , Spermatogenesis/genetics , Terminal Repeat Sequences/genetics , Terminal Repeat Sequences/physiology
16.
Cell Mol Biol (Noisy-le-grand) ; 66(3): 119-124, 2020 Jun 05.
Article in English | MEDLINE | ID: mdl-32538757

ABSTRACT

This study aims to study the effect and mechanism of Patrinia herba aqueous extract on proliferation, apoptosis, invasion and migration of hepatocellular carcinoma cells. Hepatocellular carcinoma cells MHCC97-H were treated with 2.5, 5, 10 mg/mL P. herba aqueous extract, cell counting kit 8 (CCK-8), flow cytometry, plate cloning experiments, and Transwell measured cell survival, apoptosis, colony formation, invasion, and migration, respectively. Real-time quantitative PCR (qPCR) and western blot were used to detect long non-coding RNA (lncRNA) HTR2A-AS1 and expression of proteins P21, Caspase-3, E-cadherin and matrix metalloproteinase-2 (MMP-2), respectively. Transfected pcDNA3.1-HTR2A-AS1 in MHCC97-H cells, or transfected si-HTR2A-AS1 and treat with 10 mg/mL P. herba aqueous extract to evaluate their roles in cell proliferation, apoptosis, invasion, and migration. Different concentrations of P. herba aqueous extract significantly reduced the survival rate, colony formation, number of migrating cells, number of invading cells, and MMP-2 protein expression of MHCC97-H cells, and obviously increased the cell apoptosis rate, the expression levels of Caspase-3, E-cadherin protein and HTR2A-AS1 (P<0.05), which were all concentration-dependent. Overexpression of HTR2A-AS1 evidently decreased the survival rate, colony formation, number of migrating cells, number of invading cells, and MMP-2 protein levels in MHCC97-H cells, while remarkably enhanced the apoptosis rate of cells, P21, Caspase-3, and E-cadherin protein levels and HTR2A-AS1 expression level (P<0.05). Inhibition of HTR2A-AS1 greatly improved the survival rate, the number of clone formation, the number of migrating cells, the number of invading cells and the expression of MMP-2 protein of MHCC97-H cells treated with P. herba aqueous extract, dramatically reducing the cell apoptosis rate, P21, Caspase-3, E-cadherin protein levels and HTR2A-AS1 expression levels (P<0.05). P. herba aqueous extract may inhibit the proliferation, invasion and migration of hepatocellular carcinoma cells by up-regulating the expression of HTR2A-AS1 in hepatocellular carcinoma cells and induce apoptosis.


Subject(s)
Apoptosis/drug effects , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cell Movement/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Patrinia/chemistry , Plant Extracts/therapeutic use , Apoptosis/genetics , Cadherins/metabolism , Carcinoma, Hepatocellular/genetics , Caspase 3/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Matrix Metalloproteinase 2/metabolism , Neoplasm Invasiveness , Phytotherapy , Plant Extracts/pharmacology
17.
Biomed Chromatogr ; 34(8): e4863, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32329073

ABSTRACT

Ziritaxestat is a first-in-class autotoxin inhibitor. The purpose of this study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometric (LC-MS/MS) method for the determination of ziritaxestat in rat plasma. The plasma sample was deproteinated using acetonitrile and then separated on an Acquity BEH C18 column with water containing 0.1% formic acid and acetonitrile as mobile phase, which was delivered at 0.4 ml/min. Ziritaxestat and the internal standard (crizotinib) were quantitatively monitored with precursor-to-product transitions of m/z 589.3 > 262.2 and m/z 450.1 > 260.2, respectively. The total running time was 2.5 min. The method showed excellent linearity over the concentration range 0.5-2000 ng/ml, with correlation coefficient >0.9987. The extraction recovery was >82.09% and the matrix effect was not significant. Inter- and intra-day precisions (RSD) were <11.20% and accuracies were in the range of -8.50-7.45%. Ziritaxestat was demonstrated to be stable in rat plasma under the tested conditions. The validated LC-MS/MS method was successfully applied to study the pharmacokinetic profiles of ziritaxestat in rat plasma after intravenous and oral administration. Pharmacokinetic results demonstrated that ziritaxestat displayed a short half-life (~3 h) and low bioavailability (20.52%).


Subject(s)
Chromatography, Liquid/methods , Imidazoles/blood , Imidazoles/pharmacokinetics , Pyrimidines/blood , Pyrimidines/pharmacokinetics , Tandem Mass Spectrometry/methods , Administration, Intravenous , Administration, Oral , Animals , Biological Availability , Imidazoles/administration & dosage , Imidazoles/chemistry , Linear Models , Male , Pyrimidines/administration & dosage , Pyrimidines/chemistry , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity
18.
Ecotoxicol Environ Saf ; 205: 111159, 2020 Dec 01.
Article in English | MEDLINE | ID: mdl-32829212

ABSTRACT

Cyanobacteria blooms are crucial environmental issues by threatening both aquatic ecosystem and human health. A biomass by-product with antimicrobial activity, pyroligneous acid (PA) was tested for its suitability for removal of the cyanobacteria Microcystis aeruginosa (M. aeruginosa) in this work. Results show that the removal efficiency could reach up to 90% in the presence of 0.45% of PA and the inhibition to M. aeruginosa growth could extend to at least 40 days. The removal mechanism was studied. Both organic acids and phenols are functional content in M. aeruginosa removal and acetic acid is the most important one. Zeta potential analysis and morphology study show that the damage of cells dominates the flocculation and sedimentation of M. aeruginosa under low PA concentration (<0.7%), and increasing PA (≥0.7%) resulted in a trend of zeta potential to zero, thus removing any "shield" and triggering flocculation. Finally, study on the phenols residual after M. aeruginosa treatment shows that it could be close to 0 in 70 h. Therefore, this work proposes a possible method for world-wide treatment of cyanobacteria bloom and a new way for further utilization of PA.


Subject(s)
Anti-Infective Agents/pharmacology , Eutrophication/drug effects , Microcystis/drug effects , Terpenes/pharmacology , Biomass , Ecosystem , Flocculation , Humans , Microcystis/growth & development , Organic Chemicals
19.
Biotechnol Bioeng ; 116(1): 28-40, 2019 01.
Article in English | MEDLINE | ID: mdl-30267585

ABSTRACT

Gas fermentation has emerged as a technologically and economically attractive option for producing renewable fuels and chemicals from carbon monoxide (CO) rich waste streams. LanzaTech has developed a proprietary strain of the gas fermentating acetogen Clostridium autoethanogenum as a microbial platform for synthesizing ethanol, 2,3-butanediol, and other chemicals. Bubble column reactor technology is being developed for the large-scale production, motivating the investigation of multiphase reactor hydrodynamics. In this study, we combined hydrodynamics with a genome-scale reconstruction of C. autoethanogenum metabolism and multiphase convection-dispersion equations to compare the performance of bubble column reactors with and without liquid recycle. For both reactor configurations, hydrodynamics was predicted to diminish bubble column performance with respect to CO conversion, biomass production, and ethanol production when compared with bubble column models in which the gas phase was modeled as ideal plug flow plus axial dispersion. Liquid recycle was predicted to be advantageous by increasing CO conversion, biomass production, and ethanol and 2,3-butanediol production compared with the non-recycle reactor configuration. Parametric studies performed for the liquid recycle configuration with two-phase hydrodynamics showed that increased CO feed flow rates (more gas supply), smaller CO gas bubbles (more gas-liquid mass transfer), and shorter column heights (more gas per volume of liquid per time) favored ethanol production over acetate production. Our computational results demonstrate the power of combining cellular metabolic models and two-phase hydrodynamics for simulating and optimizing gas fermentation reactors.


Subject(s)
Butylene Glycols/metabolism , Carbon Monoxide/metabolism , Clostridium/metabolism , Ethanol/metabolism , Fermentation , Metabolic Engineering , Bioreactors/microbiology , Clostridium/genetics , Clostridium/growth & development , Hydrodynamics
20.
J Clin Gastroenterol ; 53(7): e276-e283, 2019 08.
Article in English | MEDLINE | ID: mdl-29912754

ABSTRACT

BACKGROUND: Computed tomography-measured visceral adipose tissue (VAT) and the distribution of VAT are highly correlated with the severity and prognosis of acute pancreatitis (AP). To date, all available data are from the overall AP patient population; no subgroup analysis has been conducted to evaluate patients with moderately severe AP or patients with hyperlipidemia acute pancreatitis (HLAP) as independent populations. Currently, studies on the relationship between VAT and HLAP are lacking. MATERIALS AND METHODS: A total of 235 patients with moderately severe AP or severe acute pancreatitis were divided into 2 groups according to whether hyperlipidemia was present: the HLAP group and the non-HLAP group. The general inpatient information was collected, and computed tomography was used to measure VAT, subcutaneous adipose tissue (SAT), total adipose tissue, and VAT/SAT (V/S). The data were subjected to t test, χ test, matrix scatter plot, logistic regression, and receiver operating characteristic analyses to evaluate the relationship between VAT and HLAP severity. RESULTS: Significant differences were observed in VAT, SAT, total adipose tissue, and triglycerides (TGs) between the HLAP group and the non-HLAP group (P<0.001). Significant correlations were observed between VAT and body mass index (r=0.425, P=0.017) and between VAT and TG (r=0.367, P=0.042). In the HLAP group, VAT, V/S, TG, and local complications may have significant effects on disease severity. The receiver operating characteristic curves showed that VAT and V/S were more reliable than TGs in evaluating disease severity [area under the curve (AUC) of VAT: 0.819, P<0.001; AUC of V/S: 0.855, P<0.001; AUC of TG: 0.671, P=0.04]. Disease severity was reliably evaluated at 139 cm, the cut-off value of VAT. The cut-off value of V/S was 1.145; high V/S was associated with extended intensive care unit stay. VAT and its distribution had no significant effects on mortality. CONCLUSIONS: For patients with moderately severe to severe HLAP, VAT was correlated with body mass index and TG. VAT and V/S were valuable factors for evaluating disease severity and prognosis. However, VAT had no effect on mortality, and VAT could not be used to evaluate patients with moderately severe to severe non-HLAP.


Subject(s)
Hyperlipidemias/physiopathology , Intra-Abdominal Fat/diagnostic imaging , Pancreatitis/physiopathology , Subcutaneous Fat/diagnostic imaging , Acute Disease , Adult , Body Mass Index , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Severity of Illness Index , Tomography, X-Ray Computed , Triglycerides/blood
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