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1.
Technol Cancer Res Treat ; 19: 1533033820963662, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33034276

RESUMO

PURPOSE: The purpose of this study was to investigate the clinical efficacy of salvage percutaneous radiofrequency ablation in patients with unresectable colorectal cancer liver metastases. METHODS: The cohort consisted of 81 patients with 126 colorectal cancer liver metastases who underwent radiofrequency ablation between January 2012 and September 2016. The clinical data and ablation data were retrospectively analyzed. The local tumor progression-free survival, overall survival, and prognostic factors were analyzed using the log-rank test and Cox regression model. RESULTS: The technique success rate was 99.21%. The primary efficacy rate was 100% at the 1-month follow-up. Minor complications were observed in 2 patients, which recovered within 1 week. The median local tumor progression-free survival time of all patients was 29.8 months. The absence of subsequent chemotherapy was an independent predictor of a shorter local tumor progression-free survival time (P < 0.001, hazard ratio: 2.823, 95% confidence interval: 1.603, 4.972). The median overall survival time was 26.8 months. A lesion size greater than 3 cm (P = 0.011, hazard ratio: 2.112, 95% confidence interval: 1.188, 3.754) and the presence of early local tumor progression (P = 0.011, hazard ratio: 2.352, 95% confidence interval: 1.217, 4.545) were related to a shorter survival time. CONCLUSIONS: Percutaneous radiofrequency ablation is safe in patients with colorectal cancer liver metastases refractory from chemotherapy. Subsequent chemotherapy is important to enhance local control. Small lesions and favorable early responses are related to prolonged overall survival.

2.
Integr Zool ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32929865

RESUMO

Seed dispersal is essential for plant recruitment and the maintenance of biodiversity. Colobine monkeys are primarily folivorous, but they also consume fruits and are often assumed to be seed predators. Although they are known to be epizoochorous seed dispersers, their role as endozoochorous seed dispersers needs reassessment. We examined potential endozoochory in golden snub-nosed monkeys (Rhinopithecus roxellana) at Dalongtan in Shennongjia National Park, central China, by assessing potential germination of ingested seeds (n = 1806, 9 species) from fecal samples. Intact seeds were in almost all fecal samples (ranging from 5-130 seeds), and ingested seeds were from small seeded species (seed width <4.5 mm). The 2 most abundant species were Actinidia arguta (73%) and Rosa caudata (15%). The fruits of A. arguta were unripe when ingested (i.e. effective seed predation) and the ingested seeds did not germinate in the trials. Therefore, ingestion of unripe seeds does not lead to effective seed dispersal. However, germination rates of defecated R. caudata (9%) were greater than control seeds (6% and 0%), demonstrating potential endozoochorous seed dispersal. Thus, colobine monkeys do indeed disperse mainly small-seeded from multi-seeded fruits through potential endozoochory and this process enhances the recruitment of seedlings.

3.
Int Immunopharmacol ; 88: 106719, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32916625

RESUMO

BACKGROUNDS: Myocardial ischemia-reperfusion injury (MI-RI) has many adverse complications with high mortality rate. In the current study, we investigated the therapeutic advantages of delivering Interleukin-37 (IL-37) by induced cardiospheres (iCS), generated from adult skin fibroblasts via somatic reprogramming, in treating the mice model MI-RI. METHODS: The mouse model of MI-RI was established and the iCS cells with IL-37 overexpression (iCS-IL37) were transplanted into the mice via tail-vein injection. Left ventricular (LV) dimensions and LV pressure-volume measurements were assessed by parasternal long-axis echocardiography and hemodynamic assessment. The infarct size was determined by histology analysis. And the inflammatory responses were analyzed by using enzyme-linked immunosorbent assay (ELISA). RESULTS: The LV function was significantly improved after the iCS-IL37 transplantation when compared to the vehicle control group and iCS group, including the end-systolic pressure and dP/dtMax. Furthermore, the infarct size was significantly decreased after the iCS-IL37 transplantation. The protein levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), were down-regulated by the iCS-IL37 transplantation. CONCLUSION: The present study indicated that the iCS with IL-37 overexpression had therapeutic effects on the mice model of MI-RI.

4.
Medicine (Baltimore) ; 99(37): e22119, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925759

RESUMO

The presence of left ventricular hypertrophy has been confirmed to be an independent risk factor for stroke and death in patients with atrial fibrillation. This retrospective study aimed to evaluate the potential risk factors for left ventricular hypertrophy in patients with atrial fibrillation.A series of consecutive patients diagnosed with atrial fibrillation between June 2018 and December 2019 were included. The patients' clinical data were analyzed. The cut-off values, sensitivity and specificity of the independent risk factors were calculated using a receiver operating characteristic curve.Among 87 patients with atrial fibrillation, 39 patients with left ventricular hypertrophy and 48 patients without left ventricular hypertrophy were included. Multivariate logistic regression analysis showed that red blood cell distribution width (odds ratio [OR] 4.89, 95% confidence interval [CI]: 1.69-14.13, P < .05) was an independent risk factor, while the concentration of low-density lipoprotein (OR 0.37, 95% CI: 0.17-0.83, P < .05) and left ventricular ejection fraction (OR 0.88, 95% CI: 0.82-0.95, P < .05) were inversely associated with left ventricular hypertrophy in atrial fibrillation patients. The receiver operating characteristic curve demonstrated that the area under the curve was 0.80 (95% CI: 0.71-0.90, P < .05) with a cut-off value of 13.05, and the red blood cell distribution width predicted left ventricular hypertrophy status among atrial fibrillation patients with a sensitivity of 72.1% and a specificity of 76.9%.Red blood cell distribution width was associated with left ventricular hypertrophy in patients with atrial fibrillation.


Assuntos
Fibrilação Atrial/sangue , Índices de Eritrócitos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico , Idoso , Fibrilação Atrial/complicações , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco
5.
Anal Chem ; 92(17): 11904-11911, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32786460

RESUMO

Single-cell analysis contributes to the understanding of cellular heterogeneity and behaviors. Nitric oxide (NO) is an important intracellular and intercellular signaling molecule, and the functions of NO are closely related to the balance between intra- and extracellular NO levels. In this manuscript, a convenient and reliable method based on a dual-labeling strategy using capillary electrophoresis (CE) separation with laser-induced fluorescence (LIF) detection has been presented for quantifying intra- and extracellular NO simultaneously in single cells. Followed by single-cell injection, a plug of HEPES buffer containing 1,3,5,7-tetramethyl-8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacene and disodium 2,6-disulfonate-1,3-dimethyl-5-hexadecyl-8-(3,4-diaminophenyl)-4,4'-difluoro-4-bora-3a,4a-diaza-s-indacene as the labeling reagents for intra- and extracellular NO, respectively, was aspirated from the inlet of the capillary. The on-line derivatization was carried out on the tip of the capillary at room temperature for 20 min. Then, the cell was lysed and NO derivatives were well separated within 14 min, producing mass detection limits (S/N = 3) of 2.4 and 8.1 amol for intra- and extracellular NO, respectively. The proposed method was validated by simultaneous analysis of intra- and extracellular NO in single macrophage cells. The dual labeling-based CE-LIF method holds great promise for research on the functions of NO as well as other bioactive molecules at the single-cell level.

6.
Chin J Nat Med ; 18(8): 573-581, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32768164

RESUMO

Pyrrosia petiolosa, Pyrrosia lingua and Pyrrosia sheareri are recorded as original plants of Pyrrosiae Folium (PF) and commonly used as Chinese herbal medicines. Due to the similar morphological features of PF and its adulterants, common DNA barcodes cannot accurately distinguish PF species. Knowledge of the chloroplast (cp) genome is widely used in species identification, molecular marker and phylogenetic analyses. Herein, we determined the complete cp genomes of three original species of PF via high-throughput sequencing technologies. The three cp genomes exhibited a typical quadripartite structure with sizes ranging from 158 165 to 163 026 bp. The cp genomes of P. petiolosa and P. lingua encoded 130 genes, whilst that of P. sheareri encoded 131 genes. The complete cp genomes were compared, and five highly divergent regions of petA-psbJ, matK-rps16, ndhC-trnM, psbM-petN and psaC-ndhE were screened as potential DNA barcodes for identification of Pyrrosia genus species. The phylogenetic tree we obtained indicated that P. petiolosa and P. lingua are clustered in a single clade and, thus, share a close relationship. This study provides invaluable information for further studies on the species identification, taxonomy and phylogeny of Pyrrosia genus species.

7.
Chin J Nat Med ; 18(8): 606-611, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32768167

RESUMO

As abscisic acid (ABA) receptor, the pyrabactin resistance 1-like (PYR/PYL) protein (named PYL for simplicity) plays an important part to unveil the signal transduction of ABA and its regulatory mechanisms. Glycyrrhiza uralensis, a drought-tolerant medicinal plant, is a good model for the mechanism analysis of ABA response and active compound biosynthesis. However, knowledge about PYL family in G. uralensis remains largely unknown. Here, 10 PYLs were identified in G. uralensis genome. Characterization analysis indicated that PYLs in G. uralensis (GuPYLs) are relatively conserved. Phylogenetic analysis showed that GuPYL1-3 belongs to subfamily I, GuPYL4-6 and GuPYL10 belong to subfamily II and GuPYL7-9 belongs to subfamily III. In addition, transcriptome data presented various expression levels of GuPYLs under different exogenous ABA stresses. The expression pattern of GuPYLs was verified by Quantitative real-time polymerase chain reaction (qRT-PCR). The study proved that GuPYL4, GuPYL5, GuPYL8 and GuPYL9 genes are significantly up-regulated by ABA stress and the response process is dynamic. This study paves the way for elucidating the regulation mechanism of ABA signal to secondary metabolites and improving the cultivation and quality of G. uralensis using agricultural strategies.

8.
Carbohydr Polym ; 246: 116595, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32747251

RESUMO

To improve the extraction efficiency of polysaccharides from Sagittaria sagittifolia L. (SPU) by ultrasonic assisted extraction (UAE), the optimal extraction conditions were optimized as follows: extraction temperature of 85℃, extraction time of 15 min and ratio of liquid to raw material 43 mL/g, under these conditions, the yield of SPU increased by about 168 % compared with hot water extraction (HWE). After separation and purification by DEAE-52 cellulose column and Sephadex G-50 column, the pure polysaccharide fraction (SPU70-W1) was obtained, and its structure, rheology and immune activity were analyzed. The results indicated that SPU70-W1 (7.70 kDa) contained mannose, glucose and galactose in the molar ratio of 2.06:93.58:4.36 with typical pseudoplasticity fluids behavior and possessed the backbone of →2,6)-α-D-Glcp-(1→, →3,6)-α-D-Glcp-(1→, α-D-Glcp-(1→ and 6)-α-D-Glcp-(1→. In addition, SPU70-W1 exhibited remarkable immunomodulatory activity. Thus, SPU70-W1 could contribute to the food, medicine, cosmetics as a functional additive.

9.
BMC Musculoskelet Disord ; 21(1): 510, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736621

RESUMO

BACKGROUND: Increased physical activity level is related to lower risk of depressive symptoms, and there is an inverse association between muscle strength and risk of depressive symptoms among the elderly. Although there is evidence of an inverse association between muscle strength and depressive symptoms, the relationship between these variables in a younger population is still unknown. This study aimed to examine the association between handgrip strength, a representative indicator of skeletal muscle strength, and the risk of depressive symptoms among Chinese female college freshmen. METHODS: A cross-sectional study was conducted among 867 participants aged between 16 and 23 years. Handgrip strength was measured with a handheld digital Smedley dynamometer, and handgrip strength relative to body weight (kg/kg) was calculated and was classified into tertiles as follows: low (0.32-0.50), medium (0.51-0.58), and high (0.59-0.94). Depressive symptoms were evaluated using the 20-item Zung self-rating depression scale (SDS), and three cutoff points were used to indicate different depression levels. RESULTS: We found that 10.7% of participants were classified as having severe depressive symptoms using an SDS score of 50 as the cutoff point. After adjusting for potential confounders, the adjusted odds ratios and 95% confidence intervals (CIs) for moderate-to-severe depressive symptoms across tertiles of the relative handgrip strength were 1.00 (reference) for tertile 1, 0.614 (0.353, 1.069) for tertile 2, and 0.537 (0.292, 0.988) for tertile 3 (P for trend = 0.041). The significant associations remained when other cutoff points (SDS scores: 48 or 45) were used. Interactions between handgrip strength and potential confounders for depressive symptoms in the final models were not significant. CONCLUSIONS: Our findings indicate that handgrip strength is inversely and independently related to the risk of depressive symptoms among Chinese female college freshmen. The present findings can help develop an effective intervention strategy against depression. Further intervention studies are needed to explore the mechanisms underlying the effects of handgrip strength on depressive symptoms.

10.
Autophagy ; : 1-17, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32627648

RESUMO

Dysregulated microRNAs (miRNAs) are involved in carcinoma progression, metastasis, and poor prognosis. We demonstrated that in nasopharyngeal carcinoma (NPC), transactivated MIR106A-5p promotes a malignant phenotype by functioning as a macroautophagy/autophagy suppressor by targeting BTG3 (BTG anti-proliferation factor 3) and activating autophagy-regulating MAPK signaling. MIR106A-5p expression was markedly increased in NPC cases based on quantitative real-time PCR, miRNA microarray, and TCGA database analysis findings. Moreover, MIR106A-5p was correlated with advanced stage, recurrence, and poor clinical outcomes in NPC patients. In addition to three-dimensional cell culture assays, zebrafish and BALB/c mouse tumor models revealed that overexpressed MIR106A-5p targeted BTG3 and accelerated the NPC malignant phenotype by inhibiting autophagy. BTG3 promoted autophagy, and its expression was correlated with poor prognosis in NPC. Attenuation of autophagy, mediated by the MIR106A-5p-BTG3 axis, occurred because of MAPK pathway activation. MIR106A-5p overexpression in NPC was due to increased transactivation by EGR1 and SOX9. Our findings may lead to novel insights into the pathogenesis of NPC. ABBREVIATIONS: ACTB: actin beta; ATG: autophagy-related; ATG5: autophagy related 5; BLI: bioluminescence; BTG3: BTG anti-proliferation factor 3; CASP3: caspase 3; ChIP: chromatin immunoprecipitation; CQ: chloroquine; Ct: threshold cycle; DAPI: 4',6-diamidino-2-phenylindole; DiL: 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate; EBSS: Earle's balanced salt solution; EGR1: early growth response 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GEO: Gene Expression Omnibus; GFP: green fluorescent protein; IF: immunofluorescence; IHC: immunohistochemistry; ISH: in situ hybridization; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MIR106A-5p: microRNA 106a-5p; miRNAs: microRNAs; MKI67: marker of proliferation ki-67; mRNA: messenger RNA; MTOR: mechanistic target of rapamycin kinase; NPC: nasopharyngeal carcinoma; qRT-PCR: quantitative real-time PCR; siRNA: small interfering RNA; SOX9: SRY-box transcription factor 9; SQSTM1: sequestosome 1; TCGA: The Cancer Genome Atlas; WB: western blot.

11.
ACS Appl Mater Interfaces ; 12(29): 33315-33324, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32618185

RESUMO

The chemical conversion films from deep eutectic solvents (DESs) have recently been shown to reduce the corrosion rate of magnesium alloys, which are recognized as a kind of promising materials applied in the human body. However, the biocompatibility of the conversion films has not been investigated. This study proposes an uncommon DES system composed of lithium chloride and urea to fabricate the chemical conversion films on Mg and its alloy. The fabrication process of the conversion film is facile, which is performed by the heat treatment of the substrate in the DES at about 200 °C for 30 min. It is found that the thermal decomposition of the DES can release hydrogen, which diffuses into the Mg substrate to form MgH2-based conversion films. The DES conversion film possesses a porous structure on pure Mg, whereas it becomes dense on the alloy with some cracks. X-ray photoelectron spectroscopy shows that MgCO3 and oxides also exist in the DES conversion films, which depends on the substrate. Electrochemical corrosion test and in vitro biocompatibility tests, including hemolysis, cytotoxicity, antibacterial, and cytoskeleton staining experiments, are performed in a simulated body environment, which shows that the corrosion resistance and biocompatibility of the substrates have been improved significantly. We expect that the DES heat treatment method will be applied to the fabrication of corrosion-resistant and biocompatible surfaces for biodegradable Mg alloys.

12.
Zhongguo Zhong Yao Za Zhi ; 45(10): 2411-2416, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32495600

RESUMO

Two new phenylpropanoid amide glycosides and ten analogues were isolated from the CH_2Cl_2 layer of 95% ethanol extract of the whole plants of Corydalis racemosa by using various chromatographic techniques, including silica gel, Sephadex LH-20, ODS column chromatographies, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, MS, NMR, and IR spectroscopic data as N-cis-sinapoyltyramine-4'-O-ß-glucoside(1), N-cis-sinapoyl-3-methoxytyramine-4'-O-ß-glucoside(2), N-cis-sinapoyltyramine(3), N-cis-feruloyltyramine(4), N-trans-cinnamoyltyramine(5), N-trans-feruloylphenethylamine(6), N-trans-p-methoxycinnamoyl-3-hydoxyoctopamine(7), N-cis-feruloyl-3-methoxytyramine(8), N-trans-feruloyltyramine(9), N-trans-feruloyl-3-methoxytyramine(10), N-trans-sinapoyltyramine(11), and N-trans-p-coumaroyltyramine(12). Compounds 1 and 2 are new compounds. Compounds 3-7 are obtained from the plants of Papaveraceae for the first time, and compounds 8-12 are firstly isolated from C. racemosa.


Assuntos
Corydalis , Amidas , Cromatografia Líquida de Alta Pressão , Glucosídeos , Glicosídeos
13.
Sci Rep ; 10(1): 9743, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546765

RESUMO

Genomic profiling studies have demonstrated that bladder cancer can be divided into two molecular subtypes referred to as luminal and basal with distinct clinical behaviors and sensitivities to frontline chemotherapy. We analyzed the mRNA expressions of signature luminal and basal genes in bladder cancer tumor samples from publicly available and MD Anderson Cancer Center cohorts. We developed a quantitative classifier referred to as basal to luminal transition (BLT) score which identified the molecular subtypes of bladder cancer with 80-94% sensitivity and 83-93% specificity. In order to facilitate molecular subtyping of bladder cancer in primary care centers, we analyzed the protein expressions of signature luminal (GATA3) and basal (KRT5/6) markers by immunohistochemistry, which identified molecular subtypes in over 80% of the cases. In conclusion, we provide a tool for assessment of molecular subtypes of bladder cancer in routine clinical practice.

14.
Dig Dis Sci ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591968

RESUMO

BACKGROUND: How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established. The present study therefore aims to investigate the microbial communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC. METHODS: Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy. The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses. RESULTS: GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients. These changes were evident in both tumor and paracancerous tissues from GC patients. Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples. Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients. In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp. abundance. Importantly, these MDI values were readily able to discriminate between GC and SG patient samples. Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community. CONCLUSIONS: GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues. Differences in the relative abundance of Helicobacter spp. may be the primary driver of gastric dysbiosis in GC patients.

15.
iScience ; 23(6): 101201, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32521509

RESUMO

We report a comprehensive molecular analysis of 34 cases of small cell carcinoma (SCC) and 84 cases of conventional urothelial carcinoma (UC), with The Cancer Genome Atlas cohort of 408 conventional UC bladder cancers used as the reference. SCCs showed mutational landscapes characterized by nearly uniform inactivation of TP53 and were dominated by Sanger mutation signature 3 associated with loss of BRCA1/2 function. SCCs were characterized by downregulation of luminal and basal markers and were referred to as double-negative. Transcriptome analyses indicated that SCCs displayed lineage plasticity driven by a urothelial-to-neural phenotypic switch with a dysregulated epithelial-to-mesenchymal transition network. SCCs were depleted of immune cells, and expressed high levels of the immune checkpoint receptor, adenosine receptor A2A (ADORA2A), which is a potent inhibitor of immune infiltration. Our observations have important implications for the prognostication and development of more effective therapies for this lethal bladder cancer variant.

16.
Clin Chim Acta ; 509: 210-216, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32562664

RESUMO

PURPOSE: The present study was performed to explore the prognostic value of prognostic nutritional index (PNI) in renal cell carcinoma (RCC) patients following nephrectomy. METHODS: A total of 660 patients were included. PNI was calculated based on the following formula: serum albumin level (g/L) + 0.005 × total lymphocyte count (per mm3). Kaplan-Meier survival curve and the log-rank test were conducted. Univariate analysis and multivariate Cox regression analysis were performed to explore the prognostic factors. RESULTS: The patients in low PNI group were more likely to be older (P < 0.001), have a larger tumor (P < 0.001), higher pathological T stage (P < 0.001), positive lymph node (P = 0.038), distant metastasis (P = 0.005), higher tumor grade (P < 0.001) and tumor necrosis (P < 0.001). Multivariable analysis revealed low preoperative PNI was an independent predictor of overall survival (OS) (P = 0.034) and progression-free survival (PFS) (P = 0.004) for all patients. Besides, low preoperative PNI was also significantly associated with poor OS (P = 0.008), cancer-specific survival (CSS) (P = 0.032) and PFS (P = 0.003) for non-metastatic RCC patients. CONCLUSION: The patients with lower preoperative PNI were associated with adverse factors. Furthermore, the low preoperative PNI was also associated with inferior oncological outcomes in RCC patients who underwent nephrectomy.

17.
Curr Opin Chem Biol ; 59: 47-53, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32460136

RESUMO

Demethylation is a chemical process widely distributed in nature to remove a methyl group from an organic molecule, which is a key aspect of diverse biological processes including biosynthesis of natural products, degradation of plant biomass and epigenetic regulation. This process is facilitated by diverse demethylases via distinct mechanisms. Recent studies have disclosed some novel demethylation reactions as well as their underlying demethylases in the biosynthesis of bacterial sterols, fungal terpenoids, and plant alkaloids. This article focuses on current advances in dissecting the demethylation reactions in biosynthesis of natural products and aims to point out the enzymatic mechanisms, which will further enhance our knowledge and understanding of demethylation process in nature.

18.
Angew Chem Int Ed Engl ; 59(32): 13531-13536, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32364293

RESUMO

The alkyne is a biologically significant moiety found in many natural products and a versatile functional group widely used in modern chemistry. Recent studies have revealed the biosynthesis of acetylenic bonds in fatty acids and amino acids. However, the molecular basis for the alkynyl moiety in acetylenic prenyl chains occurring in a number of meroterpenoids remains obscure. Here, we identify the biosynthetic gene cluster and characterize the biosynthetic pathway of an acetylenic meroterpenoid biscognienyne B based on heterologous expression, feeding experiments, and in vitro assay. This work shows that the alkyne moiety is constructed by an unprecedented cytochrome P450 enzyme BisI, which shows promiscuous activity towards C5 and C15 prenyl chains. This finding provides an opportunity for discovery of new compounds, featuring acetylenic prenyl chains, through genome mining, and it also expands the enzyme inventory for de novo biosynthesis of alkynes.

19.
Genome Med ; 12(1): 41, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32349779

RESUMO

BACKGROUND: Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy is widely used in peripheral T cell lymphoma (PTCL). Here we conducted a phase 2, multicenter, randomized, controlled trial, comparing the efficacy and safety of CEOP/IVE/GDP alternating regimen with CEOP in newly diagnosed PTCL. METHODS: PTCL patients, except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, were 1:1 randomly assigned to receive CEOP/IVE/GDP (CEOP, cyclophosphamide 750 mg/m2, epirubicin 70 mg/m2, vincristine 1.4 mg/m2 [maximum 2 mg] on day 1, and prednisone 60 mg/m2 [maximum 100 mg] on days 1-5 every 21 days, at the first and fourth cycle; IVE, ifosfamide 2000 mg/m2 on days 1-3, epirubicin 70 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1-3 every 21 days, at the second and fifth cycle; and GDP, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1-3, and dexamethasone 40 mg on days 1-4 every 21 days, at the third and sixth cycle) and CEOP (every 21 days for 6 cycles). Analysis of efficacy and safety was of the intent-to-treatment population. The primary endpoint was a complete response rate at the end of treatment. Meanwhile, whole exome sequencing and targeted sequencing were performed in 62 patients with available tumor samples to explore prognostic biomarkers in this cohort as an exploratory post hoc analysis. RESULTS: Among 106 patients, 53 each were enrolled to CEOP/IVE/GDP and CEOP. With 51 evaluable patients each in two groups, a complete response rate of the CEOP/IVE/GDP group was similar to that of the CEOP group (37.3% vs. 31.4%, p = 0.532). There was no difference in median progression-free survival (PFS; 15.4 months vs. 9.2 months, p = 0.122) or overall survival (OS; 24.3 months vs. 21.9 months, p = 0.178). Grade 3-4 hematological and non-hematological adverse events were comparable. Histone modification genes were most frequently mutated (25/62, 40.3%), namely KMT2D, KMT2A, SETD2, EP300, and CREBBP. Multivariate analysis indicated that CREBBP and IDH2 mutations were independent factors predicting poor PFS and OS (all p < 0.001), while KMT2D predicting poor PFS (p = 0.002). CONCLUSIONS: CEOP/IVE/GDP alternating regimen showed no remission or survival advantage to standard chemotherapy. Future clinical trials should aim to develop alternative regimen targeting disease biology as demonstrated by recurrent mutations in epigenetic factors. TRIAL REGISTRATION: The study was registered on ClinicalTrial.gov (NCT02533700) on August 27, 2015.

20.
Biosci Rep ; 40(6)2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32441302

RESUMO

Ultrasound-guided costoclavicular block (CC-approach) is a recently described brachial plexus block (BPB) and an alternative approach to the supraclavicular approach (SC-approach). The relevant sonoanatomy is analogous in terms of the brachial plexus and its adjacent artery for both approaches. In the present study, we hypothesized that the two approaches will result in similar block dynamics when used the modified double-injection (MDI) technique. One hundred and twelve patients were randomly allocated to receive either a SC- or CC-approach with MDI technique. In the CC group, half the volume was injected adjacent to the medial cord of the brachial plexus, the procedure was guided by ultrasound and verified by nerve stimulator, subsequently the second half was injected close to the lateral cord. In the SC group, the MDI technique was carried out as described in our previous study. Sensory and motor blockade of all four terminal nerves were assessed with a 3-point scale. The primary outcome was the proportion of complete sensory blockade at 15 min with a predefined non-inferiority margin of -13%. The proportion of subjects at 15 min was comparable between the SC group and the CC group (91 vs 87%, absolute difference: -3%). No significant differences were found for complete motor blockade and onset times of the individual nerves within 30 min, and block-related serious adverse events (all P>0.05). We conclude that the MDI technique applied to a costoclavicular and supraclavicular block resulted in similar block dynamics. In addition, it may provide a promising alternative technique when considering the use of multipoint injection.

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