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1.
Diabetes ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404350

RESUMO

m6A RNA modification is essential during embryonic development of various organs; however, its role in embryonic and early postnatal islet development remains unknown. Mice in which RNA methyltransferase-like 3/14 (Mettl3/14) were deleted in Ngn3+ endocrine progenitors (Mettl3/14 nKO ) developed hyperglycemia and hypo-insulinemia at 2 weeks after birth. We found that Mettl3/14 specifically regulated both functional maturation and mass expansion of neonatal ß cells before weaning. Transcriptome and m6A methylome analyses provided m6A-dependent mechanisms in regulating cell identity, insulin secretion and proliferation in neonatal ß cells. Importantly, we found that Mettl3/14 were dispensable for ß cell differentiation, but directly regulated essential transcriptional factor MafA expression at least partially via modulating its mRNA stability and failure to maintain this modification impacted the ability to fulfill ß cell functional maturity. In both diabetic db/db mice and type 2 diabetes patients, decreased Mettl3/14 expression in ß cells were observed, suggesting its possible role in type 2 diabetes. Our study unraveled the essential role of Mettl3/14 in neonatal ß cell development and functional maturation, both of which determined functional ß cell mass and glycemic control in adulthood.

2.
Int J Biol Macromol ; 157: 340-349, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32335105

RESUMO

Brigatinib, a multi-target kinase inhibitor, is primarily used to treat anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small cell lung cancer (NSCLC) who have previously received crizotinib or are resistant to crizotinib. In this study, we focused on elucidating the interaction mechanism between brigatinib and human alpha-1-acid glycoprotein (HAG) through experimental and computational approaches. Steady-state fluorescence and UV-vis spectroscopy measurements revealed that brigatinib could quench the intrinsic fluorescence of HAG in a static quenching manner and formed the brigatinib-HAG complex with the stoichiometric ratio of 1:1. The findings revealed that brigatinib had a stronger affinity on HAG due to higher binding constant of 2.91 × 105 M-1 at 298 K. It can be proved from thermodynamic parameter analysis that brigatinib spontaneously bound to HAG in the means of enthalpy driven, the main forces for stabilizing brigatinib-HAG complexes were hydrogen bonding and hydrophobic interactions. The experimental results also indicated that the binding interaction induced micro-environmental changes around tryptophan residues and the alteration in secondary structure of HAG. The presence of metal ions like Mg2+, Zn2+, Ca2+, Ni2+ and Co2+ affects the binding interaction and thus change the therapeutic efficacy of brigatinib. Molecular docking results suggested that brigatinib was embedded to the hydrophobic cavity of HAG. The experimental and computational results certified that hydrogen bonding and hydrophobic interaction as well as electrostatic energy and van der Waals forces plays a leading role in the binding process.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32280033

RESUMO

BACKGROUND: Both hospital-acquired infection (HAI) and cancer represents major health concerns worldwide, but there is a paucity of data describing HAI in Chinese cancer patients. The objective of this study is to demonstrate the prevalence, causative agents, antimicrobial use and risk factors for HAI in a cancer hospital in Southwestern China. METHODS: We use the criteria of the Ministry of Health of the People's Republic of China to define hospital-acquired infections. One-day cross-sectional surveys were annually conducted from 2014 to 2018. Trained staff collected hospital-acquired infections, antimicrobial use and clinical characteristics data of inpatients. Multivariate logistic regression was used to determine the potential risk factors associated with HAIs. RESULTS: Of the 6717 patients surveyed, there were 140 patients (2.1%, 95% confidence interval, 1.7-2.4%) with 144 distinct HAIs. Lower respiratory tract infections (47, 32.6%) and surgical-site infections (29, 20.1%) were the most common HAIs. Escherichia coli was the most common pathogen (29.6%). Risk factors for HAI included younger age (<18 years) or older age (>65 years), hospitalization in the intensive care unit, presence of central catheter and undergoing surgery in the previous 30 days. The overall prevalence of patients receiving antimicrobial agents was 15.2%. CONCLUSION: To control hospital-acquired infections in cancer patients, surveillance and prevention strategies to infections associated with central catheters or related to surgery should be augmented.

4.
Bioorg Chem ; 99: 103847, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32311581

RESUMO

Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor which accounts for about 10-20% of childhood brain tumors. The survival rate for DIPG remains very poor, with a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of a large number of clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care for DIPG. In the current study, we screened a natural product library and for the first time identified 6 natural compounds displaying inhibitory effects on DIPG proliferation and anchorage-independent growth through inducing tumor cell apoptosis and cell cycle arrest. Subsequent RNA-Sequencing and functional validation revealed the molecular mechanisms of these compounds with anti-DIPG activities, and identified new cellular factors such as Fibronectin 1 (FN1) and Eukaryotic translation initiation factor 3 subunit C-like (EIF3CL), required for DIPG survival as potential therapeutic targets. Our study provides promising directions to fight against this deadly pediatric cancer.

5.
J Stroke Cerebrovasc Dis ; 29(5): 104764, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32173230

RESUMO

OBJECTIVE: Aphasia is one of the most severe symptoms in stroke patients, affecting one-third of acute stroke patients. We aimed to investigate the prevalence and outcomes of aphasia in patients with acute ischemic stroke (AIS). METHODS: We computed the weighted prevalence of aphasia in AIS patients using the 2003 to 2014 National Inpatient Sample databases. Crude regression model, multivariable regression model, and propensity score matching were used to evaluate the impact of aphasia on the clinical outcomes in AIS patients. We performed the Subpopulation Treatment Effect Pattern Plot (STEPP) analyses in propensity score matching cohort to visually display the effect of interaction between aphasia and age on the clinical outcomes. RESULTS: A total of 16.93% of 4,339,156 AIS patients identified were with aphasia. The proportion of patients with comorbid aphasia increased from 13.34% in 2003 to 21.94% in 2014 (P < .0001). The results of both multivariable regression model and propensity score matching analyses indicated aphasia in AIS as a risk factor for in-hospital deaths. Aphasia was linked to prolonged length of stay (0.66 day, P < .0001) and high hospitalization cost ($971.35, P < .0001). In the STEPP analyses, in-hospital mortality rate increased with age, and the rate was higher in patients with aphasia, but the ratios decreased with an increase in age. CONCLUSIONS: Prevalence of comorbid aphasia with AIS is increasing, and it has a significant impact on clinical outcomes. Additionally, aphasia shows a greater impact on survival and medical burden among young patients with AIS.

6.
ACS Appl Mater Interfaces ; 12(15): 17936-17948, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32208630

RESUMO

To improve water solubility and bioavailability, curcumin (Cur) was encapsulated by liposomes (Cur-Lip), which was further coated with thiolated chitosan (CSSH) to form liposomal hydrogels (CSSH/Cur-Lip gel). The hydrogels were thermosensitive with in situ injectable performance, which were fluidic at room temperature and gelled quickly at 37 °C. The cumulative release ratio of the 200 µM CSSH/Cur-Lip gel was 31.57 ± 1.34% at 12 h, which could effectively delay the release of curcumin. Worthily, the resilient hydrogels were compressive even after five cycles of compression. The cytotoxicity test indicated that the liposomal hydrogels had good cytocompatibility, but after encapsulation of curcumin, MCF-7 cells were suppressed and killed dramatically after 72 h. The in vivo breast cancer recurrence experiment showed that the CSSH/Cur-Lip gel inhibited breast cancer recurrence after tumors were resected, and the tissue of defect in the CSSH/Cur-Lip gel group was repaired. The results showed that the drug-loaded liposomal hydrogels can deliver curcumin continuously and exerted an excellent tumoricidal effect in vitro and in vivo. The injectable, in situ-formable, and thermosensitive CSSH/Cur-Lip gel can be designed as a promising novel drug delivery vehicle to be used as carriers for local accurate and sustained drug delivery to minimize burst release and as tissue engineering scaffolds for tissue regeneration after tumor resection.

7.
Anal Chim Acta ; 1105: 162-168, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32138915

RESUMO

Nanozymes, or nanomaterials that mimic the behaviors of enzymes, are highly promising materials for biomedical applications because of their excellent chemical stability under harsh conditions, simple preparation method and lower costs compared with natural enzymes. We herein report the intrinsic oxidase-mimicking activity of molybdenum oxide nanoparticles (MoO3 NPs). MoO3 NPs catalyzed the oxidation of colorless 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) to green product. The catalytic mechanism of the oxidase-mimicking activity of the MoO3 NPs was investigated in detail using electron spin resonance and a radical inhibition method. The oxidation of ABTS stems from 1O2 generated from the interaction between MoO3 NPs and dissolved oxygen in the solution. Acid phosphatase (ACP) catalyzes the hydrolysis of the ascorbic acid 2-phosphate (AAP) substrate to produce ascorbic acid (AA). AA was found to fade the coloration process of the MoO3 NP-mediated ABTS oxidation. By combining the oxidase-mimicking property of the MoO3 NPs and the ACP-catalyzed hydrolysis of AAP, a novel and simple colorimetric method for detecting ACP was established. The linear range for ACP determination is 0.09-7.3 U/L with a detection limit of 0.011 U/L. This new colorimetric method was successfully applied to the detection of ACP in diluted human serum samples and screening of ACP inhibitors. The present study proposes MoO3 NPs as a new oxidase mimic for establishing various biosensing method.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 232: 118160, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32113179

RESUMO

Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor for mainly treating non-small cell lung cancer (NSCLC). This investigation focused on to clarify in detail the binding behavior between human α-1 acid glycoprotein (HAG) and ceritinib by means of multi-spectroscopic and molecular modeling approaches. Fluorescence data obtained at four different temperatures indicated ceritinib quenched the endogenous fluorescence of HAG by a static quenching mechanism. Based on the Kb value at 105 M-1 level, it can be inferred that the binding affinity between both is strong. From findings of thermodynamic parameter analysis, the competitive experiments with ANS and sucrose as well as molecular dynamic (MD) simulation, it can be inferred that hydrophobicity, hydrogen bonding, van der Waals forces as well as electrostatic interactions exist in the binding interaction between ceritinib and HAG. The findings from UV absorption, circular dichroism, and synchronous fluorescence spectroscopy indicated that the change in the microenvironment around the protein structure, secondary structure and tryptophan residues occurred after interaction with ceritinib. The data from FRET analysis confirmed that the non-radiative energy transfer between the two existed and the binding distance between the acceptor (ceritinib) and donor (HAG) was 2.11 nm. Meantime, the influence of Ca2+, Cu2+, Ni2+, Co2+, and Zn2+ ions on the binding interaction of ceritinib with HAG were obvious, especially Zn2+ ion.

10.
J Am Chem Soc ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32207939

RESUMO

Here we propose a strategy of radical oxidation reaction for the high-efficiency production of graphene oxide (GO). GO plays important roles in the sustainable development of energy and the environment, taking advantages of oxygen-containing functional groups for good dispersibility and assembly. Compared with Hummers' method, electrochemical exfoliation of graphite is considered facile and green, although the oxidation is fairly low. To synthesize GO with better crystallinity and higher oxidation degree, we present a photosynergetic electrochemical method. By using oxalate anions as the intercalation ions and co-reactant, the interfacial concentration of hydroxyl radicals generated during electrochemical exfoliation was promoted, and the oxidation degree was comparable with that of GO prepared by Hummers' method. In addition, the crystallinity was improved with fewer layers and larger size. Moreover, the aniline coassembled GO membrane was selectively permeable to water molecules by the hydrogen-bond interaction, but it was impermeable to Na+, K+, and Mg2+, due to the electrostatic interactions. Thus, it has a prospective application to water desalination and purification. This work opens a novel approach to the direct functionalization of graphene during the electroexfoliation processes and to the subsequent assembly of the functionalized graphene.

11.
Medicine (Baltimore) ; 99(12): e19496, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195949

RESUMO

BACKGROUND: Dysmenorrhea seriously affects the ability of women to perform normal social activities and decreases their quality of life. Primary dysmenorrhea can be effectively treated with acupuncture. Based on the wrist-ankle acupuncture (WAA) theory, we designed a portable WAA point compression treatment strap that treats diseases by automatically applying pressure to acupuncture points. The proposed study aims to evaluate the immediate analgesic effect of the acupressure wrist-ankle strap in patients with primary dysmenorrhea. METHODS: The study will be a randomized controlled trial conducted from May 1, 2019 to May 30, 2020 that includes 78 students from Shanghai University of Traditional Chinese Medicine who have primary dysmenorrhea and meet the eligibility criteria. Participants will be randomly divided into 2 groups in a 1:1 allocation ratio. The intervention group will use the acupressure wrist-ankle strap equipped with tip compression component parts on the internal side; the control group will use the nonacupressure wrist-ankle strap with the tip compression parts removed. All participants will be treated for 30 minutes on the 1st day of menstruation. The primary outcome is the pain intensity score measured by the visual analog scale. The secondary outcomes are the onset time of analgesia, the pain threshold at Yinlingquan (SP 9), skin temperature at Guanyuan (CV 4), and expectations and satisfaction of patients as investigated via the expectation and treatment credibility scale. DISCUSSION: This trial will be the 1st study to evaluate the analgesic effect of the acupressure wrist-ankle strap in patients with primary dysmenorrhea. The quality of this study is ensured by the randomization, nonacupressure control, and blinded design. The results may provide evidence for a potential alternative treatment for primary dysmenorrhea and evidence-based proof of the analgesic effect of WAA.


Assuntos
Acupressão/efeitos adversos , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Dismenorreia/terapia , Analgesia por Acupuntura/instrumentação , Analgesia por Acupuntura/estatística & dados numéricos , Adolescente , Adulto , Tornozelo , China/epidemiologia , Dismenorreia/epidemiologia , Dismenorreia/psicologia , Feminino , Humanos , Limiar da Dor , Satisfação do Paciente , Qualidade de Vida , Escala Visual Analógica , Punho , Adulto Jovem
12.
Curr Med Sci ; 40(1): 145-154, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166677

RESUMO

Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy. In this study, polyethylene glycol (PEG)-coated magnetic polymeric liposome (MPL) nanoparticles (NPs) assembled from octadecyl quaternized carboxymethyl chitosan (OQC), PEGylated OQC, cholesterol, and magnetic NPs, and functionalized with epithelial growth factor receptor (EGFR) peptide, were successfully prepared for in-vivo liver targeting. The two-step liver targeting strategy, based on both magnetic force and EGFR peptide conjugation, was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse. The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force, but could also diffuse into tumor cells as a result of EGFR targeting. In addition, paclitaxel (PTX) was incorporated into small EGFR-conjugated MPLs (102.0±0.7 nm), resulting in spherical particles with high drug encapsulation efficiency (>90%). The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels. In conclusion, PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.

13.
Nat Commun ; 11(1): 613, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001690

RESUMO

Osmoregulation is important for plant growth, development and response to environmental changes. SNF1-related protein kinase 2s (SnRK2s) are quickly activated by osmotic stress and are central components in osmotic stress and abscisic acid (ABA) signaling pathways; however, the upstream components required for SnRK2 activation and early osmotic stress signaling are still unknown. Here, we report a critical role for B2, B3 and B4 subfamilies of Raf-like kinases (RAFs) in early osmotic stress as well as ABA signaling in Arabidopsis thaliana. B2, B3 and B4 RAFs are quickly activated by osmotic stress and are required for phosphorylation and activation of SnRK2s. Analyses of high-order mutants of RAFs reveal critical roles of the RAFs in osmotic stress tolerance and ABA responses as well as in growth and development. Our findings uncover a kinase cascade mediating osmoregulation in higher plants.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Arabidopsis/fisiologia , Pressão Osmótica , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Estresse Fisiológico , Quinases raf/metabolismo , Análise Mutacional de DNA , Mutação/genética , Fosfoproteínas/metabolismo , Fosforilação , Ligação Proteica
14.
DNA Cell Biol ; 39(4): 661-670, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32101022

RESUMO

Fibroblast growth factor 21 (FGF21) is a hormone-like member of the FGF family that is associated with cell death in atherosclerosis. However, its underlying mechanisms remain unclear. In this study, the effect of FGF21 on endothelial cell pyroptosis and its potential mechanisms were investigated. Results showed that FGF21 inhibits oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis and related molecular expression in human umbilical vein endothelial cells (HUVECs). Mitochondrial function was damaged by ox-LDL and restored by FGF21. A mechanism proved that ubiquinol cytochrome c reductase core protein I (UQCRC1) was downregulated by ox-LDL and upregulated by FGF21. Further, the silencing of UQCRC1 aggravated HUVEC pyroptosis and impaired mitochondrial function and reactive oxygen species (ROS) production. Moreover, Tet methylcytosine dioxygenase (TET2) was involved in the regulation of UQCRC1 expression and pyroptosis. In summary, FGF21 inhibited ox-LDL-induced HUVEC pyroptosis through the TET2-UQCRC1-ROS pathway.


Assuntos
Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/metabolismo , Piroptose/fisiologia , Aterosclerose/patologia , Sobrevivência Celular , Células Cultivadas , Proteínas de Ligação a DNA/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/genética , Fatores de Crescimento de Fibroblastos/genética , Humanos , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 230-234, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027282

RESUMO

OBJECTIVE: to explore the value of capillary electrophoresis in screening ß- thalassemia of children, and to establish the cutoff values of HbA2 and HbF in our laboratory. METHODS: The data of hemoglobin capillary electrophoresis and genetic diagnosis of ß- thalassemia from 886 examined children were retrospectively analyzed. The cutoff values of HbA2 and HbF were determined by ROC curve. RESULTS: The cutoff value of HbA2 screening minor ß- thalassemia was 3.65%, the specificity was 0.996, and the sensitivity was 0.995. The cut-off value of HbF for screening minor ß- thalassemia was 1.45%, specificity was 0.751 and sensitivity was 0.675. Thus, 1 case with codon5 (CCT→C) mutation, 1 case with SEA -HPFH ß deletion, 1 case with - 28 (A→G) merger IVS-Ι-128 (T→G) double heterozygous mutations yet were found out, 1 case with 47 bp ß gene missing has not yet been reported in literature. CONCLUSION: Capillary electrophoresis has more high sensitivity and specificity in the screening of ß- thalassemia in children, especially for the detection of rare ß- thalassemia.


Assuntos
Talassemia , Criança , Eletroforese Capilar , Hemoglobina Fetal , Hemoglobina A2 , Humanos , Estudos Retrospectivos
17.
Development ; 147(6)2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32094118

RESUMO

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.

18.
J Cell Physiol ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32020591

RESUMO

Long noncoding RNAs (lncRNAs) have been reported to dysregulate and involve in the pathology of hepatocellular carcinoma (HCC). Nonetheless, the functional role of lncRNA T cell leukemia/lymphoma 6 (TCL6) and its underlying mechanism in HCC remain unclear. Herein, we analyzed the expression of TCL6 and elucidated its mechanistic involvement in HCC. Bioinformatics analyses indicated TCL6 was evidently downregulated in HCC tissues compared with normal controls. TCL6 was downregulated while microRNA-106a-5p (miR-106a-5p) was upregulated in HCC cell lines. Moreover, knockdown or overexpression of TCL6 significantly raised or diminished the expression level of miR-106a-5p in HCC cells, similar to the effect of miR-106a-5p on TCL6 expression. Functionally, TCL6 inhibited the proliferative, migratory, and invasive potentials of HCC cells as analyzed by cell counting kit-8, scratch wound healing, and transwell assays, respectively. Conversely, miR-106a-5p exerted an opposite effect on the proliferative, migratory, and invasive potentials of HCC. RNA immune precipitation and luciferase reporter assays revealed TCL6 directly bound to miR-106a-5p and luciferase reporter assay verified phosphatase and tensin homolog (PTEN) was a target gene of miR-106a-5p. Mechanistically, TCL6 knockdown evidently reduced PTEN expression at both messenger RNA and protein levels, and miR-106a-5p inhibitor partially rescued this reduction effect in HCC cells. Additionally, western blot assays demonstrated miR-106a-5p downregulation or TCL6 overexpression promoted the protein level of PTEN, and suppressed the phosphorylation level of AKT, the protein level of phosphatidylinositol 3-kinase (PI3K). Collectively, these results revealed TCL6 as a tumor-suppressive lncRNA regulates PI3K/AKT signaling pathway via directly binding to miR-106a-5p in HCC. This mechanism provides a theoretical basis for HCC pathogenesis and a potential therapeutic strategy for HCC treatment.

19.
Cell Res ; 30(3): 256-268, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32047271

RESUMO

Meiotic recombination is initiated by the formation of double-strand breaks (DSBs), which are repaired as either crossovers (COs) or noncrossovers (NCOs). In most mammals, PRDM9-mediated H3K4me3 controls the nonrandom distribution of DSBs; however, both the timing and mechanism of DSB fate control remain largely undetermined. Here, we generated comprehensive epigenomic profiles of synchronized mouse spermatogenic cells during meiotic prophase I, revealing spatiotemporal and functional relationships between epigenetic factors and meiotic recombination. We find that PRDM9-mediated H3K4me3 at DSB hotspots, coinciding with H3K27ac and H3K36me3, is intimately connected with the fate of the DSB. Our data suggest that the fate decision is likely made at the time of DSB formation: earlier formed DSBs occupy more open chromatins and are much more competent to proceed to a CO fate. Our work highlights an intrinsic connection between PRDM9-mediated H3K4me3 and the fate decision of DSBs, and provides new insight into the control of CO homeostasis.

20.
Carbohydr Polym ; 230: 115710, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887922

RESUMO

It is urgently needed for effective treatments of extensive skin loss, wherein lack of angiogenesis is a major obstacle. In this study, we present a thermosensitive thiolated chitosan (CSSH) hydrogel conjugated with Histatin1 (Hst1) as a wound dressing to study its efficacy in enhancing the cell adhesion, spreading, migration, and angiogenesis. The composite hydrogels with gelation time of 5-7 min, showed a prolonged release of Hst1. Cell culture indicated that the adhesion, spreading, migration and tubule formation of HUVECs were promoted, especially for the Hst1-H group. The in vivo healing evaluation showed that the rate of recovery in Hst1-H group was increased to 84% at day 7, and the CD31 positive cells, vascular endothelial growth factor (VEGF) positive cells and aligned collagen fibers were significantly more than the controlled groups. Therefore, CSSH/Hst1 hydrogel is a promising candidate for wound healing by accelerating cell adhesion, migration and angiogenesis.

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