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1.
Gene ; 808: 145996, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34634440

RESUMO

Russula griseocarnosa is a well-known ectomycorrhizal mushroom, which is mainly distributed in the Southern China. Although several scholars have attempted to isolate and cultivate fungal strains, no accurate method for culture of artificial fruiting bodies has been presented owing to difficulties associated with mycelium growth on artificial media. Herein, we sequenced R. griseocarnosa genome using the second- and third-generation sequencing technologies, followed by de novo assembly of high-throughput sequencing reads, and GeneMark-ES, BLAST, CAZy, and other databases were utilized for functional gene annotation. We also constructed a phylogenetic tree using different species of fungi, and also conducted comparative genomics analysis of R. griseocarnosa against its four representative species. In addition, we evaluated the accuracy of one already sequenced genome of R. griseocarnosa based on the internal transcribed spacer (ITS) sequencing of that type of species. The assembly process resulted in identification of 230 scaffolds with a total genome size of 50.67 Mbp. The gene prediction showed that R. griseocarnosa genome included 14,229 coding sequences (CDs). In addition, 470 RNAs were predicted with 155 transfer RNAs (tRNAs), 49 ribosomal RNAs (rRNAs), 41 small noncoding RNAs (sRNAs), 42 small nuclear RNAs (snRNAs), and 183 microRNAs (miRNAs). The predicted protein sequences of R. griseocarnosa were analyzed to indicate the existence of carbohydrate-active enzymes (CAZymes), and the results revealed that 153 genes encoded CAZymes, which were distributed in 58 CAZyme families. These enzymes included 78 glycoside hydrolases (GHs), 34 glycosyl transferases (GTs), 30 auxiliary activities (AAs), 2 carbohydrate esterases (CEs), 8 carbohydrate-binding modules (CBMs), and only one polysaccharide lyase (PL). Compared with other fungi, R. griseocarnosa had fewer CAZymes, and the number and distribution of CAZymes were similar to other mycorrhizal fungi, such as Tricholoma matsutake and Suillus luteus. Well-defined effector proteins that were associated with mycorrhiza-induced small-secreted proteins (MiSSPs) were not found in R. griseocarnosa, which indicated that there may be some special effector proteins to interact with host plants in R. griseocarnosa. The genome of R. griseocarnosa may provide new insights into the energy metabolism of ectomycorrhizal (ECM) fungi, a reference to study ecosystem and evolutionary diversification of R. griseocarnosa, as well as promoting the study of artificial domestication.

2.
Sci Total Environ ; 806(Pt 1): 150507, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34583075

RESUMO

Chlorella pyrenoidosa was exposed to nonylphenol (NP) to investigate the tolerance, antioxidant response, removal efficiency, and biodegradation mechanism. We conducted studies on algal biomass, chlorophyll a content, and photosynthetic activity, and found that C. pyrenoidosa exhibited a high tolerance even at 8 mg L-1 of NP. Changes in peroxidase (POD) and superoxide dismutase (SOD) activities indicated that the NP-induced oxidative stress caused oxidant damage, which increased the malondialdehyde (MDA) content. After culturing for 120 h, the NP removal efficiency of C. pyrenoidosa was 89%, 59%, 49%, and 48% in the 2, 4, 6, and 8 mg L-1 treatment groups, respectively. Degradation intermediates determined by GC-MS suggested that the biodegradation of NP in C. pyrenoidosa originated from the long alkyl chain. In addition, transcriptome analysis indicated that NP affected photosynthesis, antioxidase, and oxidoreductase activity-related genes. In summary, our results indicated that C. pyrenoidosa is a species that exhibits high tolerance and biodegradation capacity toward NP.


Assuntos
Chlorella , Poluentes Químicos da Água , Antioxidantes , Clorofila , Clorofila A , Perfilação da Expressão Gênica , Fenóis , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
3.
World J Clin Cases ; 9(30): 9122-9128, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34786395

RESUMO

BACKGROUND: Accessory and cavitated uterine mass (ACUM) is an uncommon form of connate Müllerian anomaly seen in young and nulliparous women, which presents as chronic periodic pelvic pain and severe dysmenorrhea. The entity is often underdiagnosed due to a broad differential diagnosis, including rudimentary uterine horn, true cavitated adenomyosis and degenerating fibroids. CASE SUMMARY: A 22-year-old woman who presented with severe dysmenorrhea and was initially misdiagnosed with cystic adenomyosis. Gynecological examination and ultrasonography were performed. The patient underwent laparoscopic excision of the mass and histopathological examination confirmed the diagnosis. Postoperatively, the patient did well, with no further dysmenorrhea. CONCLUSION: ACUM is difficult to diagnose. A correct diagnosis can be made only after excision and histopathological evaluation. Surgical excision is necessary and can be carried out by laparoscopy.

4.
ChemSusChem ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811943

RESUMO

Downsizing the catalyst to atom scale offers an effective way to maximize the atom utilization efficiency for electrocatalytic nitrogen reduction reaction (NRR). Herein, single-atomic ruthenium (Ru) anchored on a chemically activated Ti 3 C 2 with O-terminated groups (Ti 3 C 2 O) is designed to catalyze the NRR process . The catalyst achieves a superior activity and selectivity with ammonia yield rate of 27.56 µg h -1 mg -1 and Faradaic efficiency of 23.3% at a low potential of -0.20 V versus the reversible hydrogen electrode. According to the atomic resolution images from aberration-corrected scanning transmission electron microscopy, Ru sites on Ti 3 C 2 O achieve well dispersion in atomic scale. X-ray photoelectron spectroscopy (XPS) analysis further demonstrates that the O-termination groups are successfully activated. Density functional theory calculations combined with experiments reveal that single Ru sites binding to four oxygen are the main reaction centers that permit the hydrogenation of *NNH 2 to *NHNH 2 in a novel distal/alternating hybrid path with reducing the energy barrier of the potential-limiting step to 0.78 eV from 0.96 eV in distal path alone or 1.18 eV in alternating path alone , thereby significantly promoting the NRR dynamics.

5.
Toxicol Lett ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34838997

RESUMO

Liver fibrosis is a reversible wound healing reaction characterized by abnormal accumulation of extracellular matrix (ECM) in response to liver injury. Recent studies have shown that it can be epigenetically regulated, especially by microRNAs (miRNAs). It has been acknowledged that activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Notably, our results showed that miR-195-3p was increased in HSCs isolated from CCl4-treated mice and that the increase was more pronounced as the degree of liver fibrosis increased. Moreover, treatment of LX-2 cells, a human immortalized hepatic stellate cell line, with TGF-ß1 resulted remarkable upregulation of miR-195-3p. Gain-of-function and loss-of-function experiments have suggested that the increased levels of miR-195-3p inhibit the expression of phosphatase and tension homolog deleted on chromosome 10 (PTEN), a negative regulator of the PI3K/Akt/mTOR signaling pathway in liver fibrosis, thereby contributing to HSC activation and proliferation and promoting the expression of profibrotic genes, such as α-SMA and collagen I, in LX-2 cells, which accelerates the accumulation of fibrous extracellular matrix deposition in the liver, while knockdown of miR-195-3p induced the opposite effect. Taken together, these results provide evidence for the harmful role of miR-195-3p in CCl4-treated mouse liver fibrosis.

6.
Medicine (Baltimore) ; 100(40): e27473, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622876

RESUMO

BACKGROUND: FOXP4-AS1 expression participates in multiple signal pathways and has been previously reported in colorectal cancer, cervical cancer, and other cancer cells. However, its role on prognosis and immune infiltrates in ovarian serous cystadenocarcinoma (OVs) remains unclear. The purpose of our study was to investigate the expression of FOXP4-AS1 in OVs and its association with immune infiltrates, and determined its prognostic roles in OVs. METHODS: Using The Cancer Genome Atlas (TCGA) database, we retrieved FOXP4-AS1 expression and clinical information for 376 patients with OVs. Wilcoxon rank sum test was used to compare the expression of FOXP4-AS1 in OVs and normal ovarian tissue. Logistic regression was used to analyze the relationship between clinicopathologic features and FOXP4-AS1. Gene Set Enrichment Analysis (GSEA), and single sample Gene Set Enrichment Analysis (ssGSEA) was conducted to investigate the enrich pathways and functions and quantify the extent of immune cells infiltration for FOXP4-AS1. Kaplan-Meier method was used to generate survival curves, and Cox regression was used to analyze the relationship between FOXP4-AS1 and survival rate. RESULTS: High FOXP4-AS1 expression was significantly correlated with tumor FIGO stage (P = .026). Multivariate survival analysis showed that FOXP4-AS1was an independent prognostic marker for overall survival (OS; hazard ratio [HR]: 0.638; 95% confidence interval [CI]:0.467-0.871; P = .001) and disease-specific survival (DSS; HR: 0.649; CI: 0.476-0.885; P = .006). GSEA showed that High FOXP4-AS1 expression may active programmed cell death 1 (PD-1) signaling, the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) pathway, the B cell receptor signaling pathway, apoptosis, fibroblast growth factor receptor (FGFR) signaling, and the Janus-activated kinase signal transducers and activators of transcription (JAK-STAT) signaling pathway. FOXP4-AS1 expression was negatively correlated with markers of immune cells, including aDC, cytotoxic cells and neutrophils. CONCLUSION: High FOXP4-AS1 expression has the potential to be a prognostic molecular marker of favorable survival in OVs.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/imunologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , RNA Longo não Codificante/biossíntese , Biomarcadores Tumorais , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico
7.
Front Cell Dev Biol ; 9: 710112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490258

RESUMO

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease caused by expanded CTG repeats in the 3' untranslated region (3'UTR) of the DMPK gene. The myogenesis process is defective in DM1, which is closely associated with progressive muscle weakness and wasting. Despite many proposed explanations for the myogenesis defects in DM1, the underlying mechanism and the involvement of the extracellular microenvironment remained unknown. Here, we constructed a DM1 myoblast cell model and reproduced the myogenesis defects. By RNA sequencing (RNA-seq), we discovered that periostin (Postn) was the most significantly upregulated gene in DM1 myogenesis compared with normal controls. This difference in Postn was confirmed by real-time quantitative PCR (RT-qPCR) and western blotting. Moreover, Postn was found to be significantly upregulated in skeletal muscle and myoblasts of DM1 patients. Next, we knocked down Postn using a short hairpin RNA (shRNA) in DM1 myoblast cells and found that the myogenesis defects in the DM1 group were successfully rescued, as evidenced by increases in the myotube area, the fusion index, and the expression of myogenesis regulatory genes. Similarly, Postn knockdown in normal myoblast cells enhanced myogenesis. As POSTN is a secreted protein, we treated the DM1 myoblast cells with a POSTN-neutralizing antibody and found that DM1 myogenesis defects were successfully rescued by POSTN neutralization. We also tested the myogenic ability of myoblasts in the skeletal muscle injury mouse model and found that Postn knockdown improved the myogenic ability of DM1 myoblasts. The activity of the TGF-ß/Smad3 pathway was upregulated during DM1 myogenesis but repressed when inhibiting Postn with a Postn shRNA or a POSTN-neutralizing antibody, which suggested that the TGF-ß/Smad3 pathway might mediate the function of Postn in DM1 myogenesis. These results suggest that Postn is a potential therapeutical target for the treatment of myogenesis defects in DM1.

8.
Sensors (Basel) ; 21(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34502680

RESUMO

Thermal energy exchange induces non-uniform temperature distribution on the concrete bridge structures, leading to variation of static and dynamic properties of structural systems. The finite element method can facilitate thermal simulation and predict the structural temperature distribution based on heat flow theories. Previous studies mainly focused on the daytime with sunny weather, and the effects of solar shadow distribution were not fully considered or even ignored. In this paper, a systematic all-weather thermal simulation method was proposed to investigate the temperature distributions of concrete maglev bridges. The solar shadow distribution on the bridge surface could be accurately simulated to determine the solar radiation-imposed range. A meteorological station and some thermocouples were installed on a real concrete maglev bridge to obtain the real-time structural temperatures and environmental conditions. Its temperature distribution is also simulated using the proposed method within the 27 monitoring days in Summer. Results show that the simulated structural temperature matches well with the measured results under various weather conditions, except that of the east structural surface. Moreover, the simulation method acquired a higher accuracy under overcast or rainy weather due to weaker solar radiation effects. Both the numerical results and experimental records illustrated that direct solar radiation dominates the thermal energy exchange under sunny or cloudy conditions. The proposed methodology for temperature field simulation is oriented by all-weather prediction of structural temperature, which is reliable for concrete bridge structures with the help of accurate measurement of real-time solar radiation.

10.
STAR Protoc ; 2(4): 100814, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34585155

RESUMO

N-Methyl-N-nitrosourea, an N-nitroso compound converted from dietary nitrite by Helicobacter pylori, causes somatic mutations in epithelial cells and induces gastric premalignancy. Here, we describe a detailed protocol for induction of gastric tumor and analysis of tumor phenotypes in mice. This model can be widely used for studying the initiation and growth of gastric cancer. For complete details on the use and execution of this protocol, please refer to Li et al. (2021).

11.
Eur J Pharmacol ; 911: 174462, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536366

RESUMO

Liver fibrosis is a persistent pathological repair of chronic liver injury, which is characterized by excessive deposition of collagen-dominated extracellular matrix (ECM). It is well known that hepatic fibrosis can be reversed in the absence of etiology. Studies have shown that long non-coding RNA (Lnc RNA) maternally expressed gene3 (MEG3) has strong effects on the activation of hepatic stellata cells (HSCs). However, the function of MEG3 in the reversal of liver fibrosis has not been studied. In this experiment, we studied the content expression, function, and part of the potential mechanism of MEG3 in reversing liver fibrosis. In in vivo and in vitro models, we found that MEG3 was down-regulated during the formation of liver fibrosis, while it was up-regulated during the reversal of liver fibrosis. Then, it was found that the silencing of MEG3 could gradually restore the activity of the inactivated LX-2 cells, Overexpression of MEG3 can inhibit the activation of LX-2 cells, accelerate the reversal of liver fibrosis. Through catRAPID analysis, it was found that NLR family CARD domain containing 5 (NLRC5) may be a target of MEG3. We found that, after MEG3 silencing, NLRC5 expression was upregulated in LX-2 cells in the reverse phase, while, after MEG3 overexpression, NLRC5 expression was decreased. Further, we verified that MEG3 can target NLRC5 through RNA pull down experiment. Therefore, MEG3 may inhibit the activation of hepatic stellate cells by targeting NLRC5, thus accelerating the reversal of hepatic fibrosis.

12.
Nat Commun ; 12(1): 5182, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462443

RESUMO

Manmade high-performance polymers are typically non-biodegradable and derived from petroleum feedstock through energy intensive processes involving toxic solvents and byproducts. While engineered microbes have been used for renewable production of many small molecules, direct microbial synthesis of high-performance polymeric materials remains a major challenge. Here we engineer microbial production of megadalton muscle titin polymers yielding high-performance fibers that not only recapture highly desirable properties of natural titin (i.e., high damping capacity and mechanical recovery) but also exhibit high strength, toughness, and damping energy - outperforming many synthetic and natural polymers. Structural analyses and molecular modeling suggest these properties derive from unique inter-chain crystallization of folded immunoglobulin-like domains that resists inter-chain slippage while permitting intra-chain unfolding. These fibers have potential applications in areas from biomedicine to textiles, and the developed approach, coupled with the structure-function insights, promises to accelerate further innovation in microbial production of high-performance materials.


Assuntos
Conectina/química , Conectina/genética , Escherichia coli/metabolismo , Fibras Musculares Esqueléticas/química , Animais , Fenômenos Biomecânicos , Conectina/metabolismo , Cristalização , Escherichia coli/genética , Expressão Gênica , Peso Molecular , Fibras Musculares Esqueléticas/metabolismo , Polimerização , Polímeros/química , Polímeros/metabolismo , Dobramento de Proteína , Coelhos
13.
J BUON ; 26(3): 677-683, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268920

RESUMO

PURPOSE: The purpose of this study was to detect the differentially expressed microRNA-186-5p in cervical cancer samples and to uncover its influence on the development of cervical cancer. METHODS: Differentially expressed microRNA-186-5p was detected in cervical cancer tissues and normal cervical tissues. Its influences on clinical features and prognosis of cervical cancer patients were analyzed. Regulatory effect of microRNA-186-5p on migratory potential in HeLa and C33-A cells was examined. In addition, the target gene binding to microRNA-186-5p was searched and its involvement in the malignant development of cervical cancer was determined. RESULTS: MicroRNA-186-5p was downregulated in cervical cancer patients, especially those with lymphatic metastasis or distant metastasis. High metastasis rate and poor prognosis were seen in cervical cancer patients expressing a low level of microRNA-186-5p. Overexpression of microRNA-186-5p inhibited migratory ability of cervical cancer cells. FZD3 was the downstream gene binding to microRNA-186-5p, which was upregulated in cervical cancer samples. Besides, it was capable of reversing the role of microRNA-186-5p in inhibiting migratory ability of cervical cancer cells. CONCLUSIONS: MicroRNA-186-5p is lowly expressed in cervical cancer samples, and it inhibits the metastasis in cervical cancer cells by targeting FZD3.

14.
J BUON ; 26(3): 684-690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268921

RESUMO

PURPOSE: The purpose of this study was to explore the safety and feasibility of laparoscopic-assisted vaginal radical trachelectomy (VRT) combined with pelvic lymph node dissection in the treatment of early-stage cervical cancer. METHODS: Patients (N=136) with early-stage cervical cancer were divided into VRT group (laparoscopic-assisted VRT combined with pelvic lymph node dissection, n=68) and abdominal radical trachelectomy (ART) group (ART combined with pelvic lymph node dissection, n=68). The operation-related indexes, incidence of postoperative complications and fertility status were compared between the two groups, and the tumor recurrence status was recorded through follow-up. The factors related to recurrence of early-stage cervical cancer were analyzed by one-way analysis of variance and Cox multivariate regression analysis. RESULTS: VRT group had significantly less intraoperative blood loss and significantly shorter postoperative ventilation time than ART group. In VRT group, the length of vaginal resection and the width of parauterine tissue resection were significantly smaller than those in ART group. The pregnancy rate in VRT group (38.6%) was far higher than that in ART group (21.2%) (p=0.041), while the fertility rate had no statistically significant difference between the two groups (90.9% vs. 81.8%) (p=0.641). The results of univariate and multivariate analysis showed that the tumor diameter was an independent risk factor for the recurrence of early-stage cervical cancer (ß=0.317, p=0.029, 95% CI=0.484-0.815). CONCLUSION: VRT is safe and feasible in the treatment of early-stage cervical cancer, which can reduce surgical damage, facilitate postoperative recovery, and effectively preserve the fertility of patients. The tumor diameter is an independent risk factor for the recurrence of early-stage cervical cancer.

15.
Biochem Biophys Rep ; 27: 101055, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34258395

RESUMO

Cinnabar has been used for treatment of various disorders for thousands of years. The medical use of cinnabar, however, has been controversial because of its heavy metal mercury content. A large quantity of studies indicate that the toxicity of cinnabar is far below other inorganic or organic mercury-containing compounds. Yet, the underlying molecular basis has remained unresolved. Here, we investigated the beneficial effects of cinnabar on serum-nutrient starvation-elicited cell injury. Our findings showed that treatment of human renal proximal tubular cells (HK-2) with 4 nM cinnabar effectively inhibited nutrient deprivation induced apoptosis, reduced intracellular reactive oxygen species generation and increased GSH content, which was contrary to the exacerbated apoptotic cell death and oxidative stress in cells treated with HgCl2 at equal mercury concentration. In addition, cinnabar exerted robust antioxidative and antiapoptotic effects in cells under dual challenges of nutrient deprivation and treatment of H2O2. The protein expression levels of both CHOP and PERK were remarkably down-regulated in the cells treated with cinnabar compared to the control cells or cells treated with HgCl2. Overall, our data indicates that cinnabar at low concentration exerts anti-oxidative stress and anti-apoptosis effects by inhibiting the expression of the endoplasmic reticulum stress pathway proteins CHOP and PERK.

16.
Phytother Res ; 35(9): 5214-5226, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34213784

RESUMO

Hawthorn (Crataegus pinnatifida Bunge. var. major) is an edible and medicinal fruit that is very common in food and traditional Chinese medicine. Corosolic acid (CA), a pentacyclic triterpenoid, which is an active component of hawthorn (Crataegus pinnatifida Bunge. var. major), has been exhibiting various pharmacological activities such as antidiabetic, antibacterial, anticancer, antiinflammatory, and antioxidant effects. The study aimed to evaluate the effect of CA on non-alcoholic steatohepatitis (NASH) in mice induced by 60 kcal% high-fat diet (HFD) and carbon tetrachloride (CCl4 ). CA lowered liver index and serum AST, ALT, TG, and TC levels compared to those in the model group. Histological analyses of the liver tissues of mice treated with CA revealed significantly decreased number of lipid droplets and alleviated inflammation and fibrosis. CA inhibited the transcripts of pro-fibrogenic markers (including α-SMA, collagen I, and TIMP-1) and the levels of pro-inflammatory cytokines (including TNF-α, IL-1ß, caspase-1, and IL-6) associated with hepatic fibrosis, and NF-κB translocation and TGF-ß1/Smad2 and AMPK pathways. In addition, CA reduced lipid accumulation via the regulation of AMPK and NF-κB activation in FFA-induced steatotic HepG2 cells. CA also decreased α-SMA, collagen I expressions, and Smad2 phosphorylation, which were reduced by TGF-ß1 treatment in LX2 cells. Our results suggested that CA ameliorated NASH through regulating TGF-ß1/Smad2, NF-κB, and AMPK signaling pathways, and CA could be developed as a potential health functional food or therapeutic agent for NASH patients.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Transdução de Sinais/efeitos dos fármacos , Triterpenos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Tetracloreto de Carbono , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Cirrose Hepática , Camundongos , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Proteína Smad2 , Fator de Crescimento Transformador beta1/metabolismo , Triterpenos/farmacologia
17.
FASEB J ; 35(7): e21700, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34105828

RESUMO

Histone deacetylases (HDACs), especially HDAC2, play a role in alleviating liver fibrosis; however, the specific upstream regulation mechanism is unknown. Herein, TargetScan was used to predict the potential upstream targets of HDAC2, and the role of miR-455-3p was explored. The dual luciferase reporter assay showed that miR-455-3p binds to the 3' UTR of HDAC2 mRNA. Additionally, miR-455-3p was downregulated in the liver tissues of patients with cirrhosis and mice with liver fibrosis, as well as in primary HSCs isolated from fibrotic mouse livers and TGF-ß-treated LX-2 cells. In contrast, it is highly expressed in the reversal stage of hepatic fibrosis and MDI-cultured LX-2 cells. Our functional analyses showed that miR-455-3p overexpression facilitated apoptosis and reduced the expression of pro-fibrotic markers and the proliferation of activated LX-2 cells. On the contrary, miR-455-3p inhibition converted inactivated LX-2 cells into activated, proliferative, fibrogenic cells. Interestingly, restoration of HDAC2 expression partially blocked the function of miR-455-3p. Downregulated miR-455-3p expression can be restored by DNA methyltransferases in activated LX-2 cells. Methylation-specific PCR, bisulfite sequencing PCR, and chromatin immunoprecipitation assays indicated that the methylation level of miR-455-3p promoter CpG islands was elevated in TGF-ß-treated LX-2 cells and that miR-455-3p was downregulated in activated LX-2 cells by DNA hypermethylation, which is mediated by DNMT3b and DNMT1. In conclusion, miR-455-3p acts as a liver fibrosis suppressor by targeting HDAC2, and its deficiency further aggravates the reversal phase of fibrosis. Thus, the epigenetics mediated miR-455-3p/HDAC2 axis may serve as a novel potential therapeutic target for clinical treatment of hepatic fibrosis.


Assuntos
Epigênese Genética , Regulação da Expressão Gênica , Histona Desacetilase 2/metabolismo , Cirrose Hepática/prevenção & controle , MicroRNAs/genética , Animais , Apoptose , Tetracloreto de Carbono/toxicidade , Proliferação de Células , Células Estreladas do Fígado/citologia , Histona Desacetilase 2/genética , Humanos , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
18.
Eur J Med Res ; 26(1): 50, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074306

RESUMO

BACKGROUND: This study is aimed to analyze the prognostic factors affecting the short-term efficacy of non-surgical treatment of patients in periodontitis from stage II to stage IV by the multilevel modeling analysis. MATERIALS AND METHODS: A total of 58 patients with chronic periodontitis were included in this study. Patients were clinically explored before and 3 months after the treatment and the difference in probing depth was determined [Reduction of probing depth (Δ PD) = baseline PD - finial probing depth (FPD)] which is considered as the therapeutic evaluation. Three different levels were analyzed: patients, teeth and sites to construct a multi-layer linear model. RESULTS: Probing depth (PD) improved significantly compared with that before treatment (p < 0.05), in which FPD was (3.90 ± 1.39) mm, and the ΔPD was (1.79 ± 0.97) mm. Compared with the mesial sites and distal sites of the multi-rooted teeth, the number of PD ≥ 5 mm or PD < 5 mm after the treatment was significantly different (P < 0.05), and the proportion of PD < 5 mm was higher in mesial sites. The null model showed that Δ PD varied greatly between groups at various levels (P < 0.001), with prediction variable of site level, tooth level, and patient level accounted for 66%, 18%, and 16% of the overall difference, respectively. The complete model showed that the Δ PD of smokers was significantly lower than that of non-smokers (P < 0.001). The Δ PD of the mesial and distal sites was larger than that of the buccolingual central site (P < 0.001). The Δ PD of single-rooted teeth was larger than that of multi-rooted teeth (P < 0.001). The baseline PD, tooth mobility (TM), bleeding index (BI), clinical attachment loss (CAL) were significantly negatively correlated with Δ PD (P < 0.001). CONCLUSIONS: Patients with periodontitis from stage II to stage IV, who were non-smoking, have good compliance, good awareness of oral health, and low percentage sites with PD ≥ 5 mm at baseline, single-rooted teeth with hypomobility, less clinical attachment loss and lower bleeding index and sites of mesial or distal can obtain an ideal short-term efficacy of non-surgical treatment.

19.
FASEB J ; 35(6): e21622, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33982351

RESUMO

Abundant regulatory genes and complex circuits involving non-coding RNAs (ncRNAs) monitor the formation and development of hepatic fibrosis (HF). Circular RNAs (circRNAs) are a class of RNAs generated from protein coding genes by back-splicing, playing crucial roles in various pathological processes, including HF. However, little is known about mechanisms of action of circRNAs, let alone in HF. In this study, we found circUbe2k enhanced in CCl4 -induced HF mice and LX-2 cells stimulated with TGF-ß1, regulating the development of HF. Restraining the expression of circUbe2k inhibited α-SMA and Col1α1 expression in CCl4 -induced HF mice and in LX-2 cells stimulated with TGF-ß1. Furthermore, inhibiting circUbe2k expression reduced hepatic stellate cells (HSCs) activation and proliferation in vivo and in vitro. Mechanistically, we demonstrated a direct interaction between circUbe2k and miR-149-5p, which results in the modulation of TGF-ß2 expressions. Together, circUbe2k may act as a "catalyst" of HSCs activation and HF through the circUbe2k/miR-149-5p/TGF-ß2 axis. Our results provide unprecedented evidence for a significant role for circUbe2k to serve as a potential biomarker for HF therapy.


Assuntos
Regulação da Expressão Gênica , Cirrose Hepática/patologia , MicroRNAs/genética , RNA Circular/genética , Fator de Crescimento Transformador beta2/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Animais , Tetracloreto de Carbono , Proliferação de Células , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fator de Crescimento Transformador beta2/genética
20.
JNCI Cancer Spectr ; 5(3): pkaa122, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34056539

RESUMO

Background: The correlation between blood-based tumor mutation burden (bTMB) and tissue-based tumor mutation burden(tTMB) has not been broadly tested in a multicancer cohort. Here, we assess the correlation between bTMB with tTMB in phase I trial patients treated with immunotherapy. As an exploratory analysis, we evaluated circulating tumor DNA (ctDNA) dynamics in responders. Methods: Patients treated with immunotherapy at the Princess Margaret phase I trials unit were enrolled. Pretreatment plasma ctDNA and matched normal blood controls were collected. Available archival tissue formalin-fixed paraffin-embedded (FFPE) samples were analyzed. A 425-gene panel was used to sequence both ctDNA and FFPE samples. Samples with TMB within the highest tertile were considered as high TMB. Results: Thirty-eight patients were accrued from 25 different trials, 86.8% of which involved an anti-PD-1/PD-L1 agent. Thirty patients (78.9%) had detectable mutations in ctDNA, of which the median (range) bTMB was 5 (1-53) mutations per megabase (mut/Mb). Of the 22 patients with available FFPE samples, mutations were detected in 21 (95.4%); the median (range) tTMB was 6 (2-124) mut/Mb. Among the 16 patients with detectable mutations in both FFPE and ctDNA, a statistically significant correlation between bTMB and tTMB was observed (ρ = 0.71; P = .002). High TMB was not associated with better survival. All 3 responders had a decrease in the variant allele frequency of mutations detected in ctDNA at a second timepoint relative to baseline, indicating a potential early marker of response. Conclusions: In this small series, bTMB correlated with tTMB. An on-treatment decrease in VAF of mutations detected in ctDNA at baseline was observed in responders. Larger studies to verify our findings are warranted.

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