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1.
BMC Public Health ; 21(1): 1648, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503467

RESUMO

BACKGROUND: Hypertension remains the major modifiable risk factor of stroke recurrence. The study aimed to determine the up-to-date epidemiological features of hypertension among the survivors of ischemic stroke. METHODS: Our cross-sectional study included 18,796 adults aged ≥40 years and residing in northeast China. Ischemic stroke was diagnosed according to the World Health Organization's criteria, which requires the clinical record, computed tomography (CT) and/or magnetic resonance imaging (MRI) during the hospital stay. Hypertension was defined according to the Chinese hypertension guidelines (mean SBP ≥140 mmHg and/or mean DBP ≥90 mmHg, and/or self-reported use of anti-hypertensive medication in the past 2 weeks). RESULTS: Of the 986 survivors of ischemic stroke, 819 (83.1%) were identified with hypertension (535 were pre-stroke hypertension and 284 were post-stroke hypertension). Among hypertensive patients, the awareness and treatment rates were 76.8 and 66.7% respectively. Only 11.0% achieved an appropriate blood pressure (< 140 mmHg and < 90 mmHg) among those who took hypertensive medications. 16.8% of treated hypertensive patients received combination therapy, and calcium channel blockers were the most frequently used anti-hypertensive medication as monotherapy. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the stroke population was 155.3 ± 22.9 mmHg and 89.2 ± 12.3 mmHg. Both SBP and DBP were higher in rural patients than in urban patients (158.5 ± 23.8 mmHg vs. 146.4 ± 17.5 mmHg and 90.3 ± 12.9 mmHg vs. 85.9 ± 10.1 mmHg, respectively; p < 0.001). The rates of stage 2 and above hypertension in the ischemic stroke population were 32.5 and 18.7%, and was significantly higher in rural areas than in urban areas. CONCLUSIONS: The prevalence of poorly-controlled hypertension and the high rates of blood pressures at stages 2 and above in patients with prior ischemic stroke demonstrated an alarming situation in northeast China.


Assuntos
Hipertensão , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , China/epidemiologia , Estudos Transversais , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Sobreviventes
2.
Cancer Lett ; 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520819

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn) in kynurenine pathway (KP) is involved in the immunosuppression in pancreatic cancer (PC), but the value of IDO1 as an independent prognostic marker for PC is uncertain. Moreover, the correlation between tryptophan 2,3-dioxygenase (TDO), an isozyme of IDO1, and PC is largely unknown. Using TCGA database, the correlation between IDO1 and/or TDO expression and PC patients' survival was analyzed. The expressions of IDO1 and TDO in PC cells and PC mice were examined. The effects of IDO1, TDO or dual inhibition on IDO1 and TDO effector pathway (Aryl hydrocarbon receptor, AhR) and on migration and invasion of PC cells were investigated. The block effect of IDO1/TDO dual inhibitor RY103 on KP was evaluated. The preclinical efficacy of RY103 and its immunomodulatory effect on KPIC orthotopic PC mice and Pan02 tumor-bearing mice were explored. Results showed that IDO1/TDO co-expression is an independent prognostic marker for PC. RY103 can significantly block KP and target Kyn-AhR pathway to blunt the migration and invasion of PC cells, exhibit preclinical efficacy and ameliorate IDO1/TDO-mediated immunosuppression in PC mice.

3.
Front Cell Infect Microbiol ; 11: 590989, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513721

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR) systems are a set of versatile gene-editing toolkit that perform diverse revolutionary functions in various fields of application such as agricultural practices, food industry, biotechnology, biomedicine, and clinical research. Specially, as a novel antiviral method of choice, CRISPR/Cas9 system has been extensively and effectively exploited to fight against human infectious viruses. Infectious diseases including human immunodeficiency virus (HIV), hepatitis B virus (HBV), human papillomavirus (HPV), and other viruses are still global threats with persistent potential to probably cause pandemics. To facilitate virus removals, the CRISPR/Cas9 system has already been customized to confer new antiviral capabilities into host animals either by modifying host genome or by directly targeting viral inherent factors in the form of DNA. Although several limitations and difficulties still need to be conquered, this technology holds great promises in the treatment of human viral infectious diseases. In this review, we will first present a brief biological feature of CRISPR/Cas9 systems, which includes a description of CRISPR/Cas9 structure and composition; thereafter, we will focus on the investigations and applications that employ CRISPR/Cas9 system to combat several human infectious viruses and discuss challenges and future perspectives of using this new platform in the preclinical and clinical settings as an antiviral strategy.

4.
Int J Mol Sci ; 22(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34502234

RESUMO

The WOX family is a group of plant-specific transcription factors which regulate plant growth and development, cell division and differentiation. From the available genome sequence databases of nine Triticeae species, 199 putative WOX genes were identified. Most of the identified WOX genes were distributed on the chromosomes of homeologous groups 1 to 5 and originated via the orthologous evolution approach. Parts of WOX genes in Triticum aestivum were confirmed by the specific PCR markers using a set of Triticum. durum-T. aestivum genome D substitution lines. All of these identified WOX proteins could be grouped into three clades, similar to those in rice and Arabidopsis. WOX family members were conserved among these Triticeae plants; all of them contained the HOX DNA-binding homeodomain, and WUS clade members contained the characteristic WUS-box motif, while only WUS and WOX9 contained the EAR motif. The RNA-seq and qPCR analysis revealed that the TaWOX genes had tissue-specific expression feature. From the expression patterns of TaWOX genes during immature embryo callus production, TaWOX9 is likely closely related with the regulation of regeneration process in T. aestivum. The findings in this study could provide a basis for evolution and functional investigation and practical application of the WOX family genes in Triticeae species.

5.
DNA Res ; 28(5)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514497

RESUMO

Phytate is the storage form of phosphorus in angiosperm seeds and plays vitally important roles during seed development. However, in crop plants phytate decreases bioavailability of seed-sourced mineral elements for humans, livestock and poultry, and contributes to phosphate-related water pollution. However, there is little knowledge about this trait in oilseed rape (Brassica napus). Here, a panel of 505 diverse B. napus accessions was screened in a genome-wide association study (GWAS) using 3.28 × 106 single-nucleotide polymorphisms (SNPs). This identified 119 SNPs significantly associated with phytate concentration (PA_Conc) and phytate content (PA_Cont) and six candidate genes were identified. Of these, BnaA9.MRP5 represented the candidate gene for the significant SNP chrA09_5198034 (27 kb) for both PA_Cont and PA_Conc. Transcription of BnaA9.MRP5 in a low-phytate variety (LPA20) was significantly elevated compared with a high-phytate variety (HPA972). Association and haplotype analysis indicated that inbred lines carrying specific SNP haplotypes within BnaA9.MRP5 were associated with high- and low-phytate phenotypes. No significant differences in seed germination and seed yield were detected between low and high phytate cultivars examined. Candidate genes, favourable haplotypes and the low phytate varieties identified in this study will be useful for low-phytate breeding of B. napus.

6.
Circ Res ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515499

RESUMO

Rationale: Timely inhibition of inflammation and initiation of resolution are important to repair injured tissues. Mammalian STE20-like protein kinase 1/2 (MST1/2) acts as a regulator of macrophage-associated immune responses to bacterial infections. However, the role of MST1/2 in regulating macrophage phenotype and function in myocardial infarction (MI) remains unclear. Objective: To determine the function and underlying mechanism of macrophage MST1/2 in cardiac repair post-MI. Methods and Results: Using LysMCre-mediated Mst1/2-deficient mice, we found that MST1 deficiency exacerbated cardiac dysfunction after MI. Single-cell RNA sequencing assay indicated that the effect was attributed to a shift of macrophage subtypes from those expressing Cxcl2 and Cd163 toward Ccl2 and Ccl4 expression. Mass spectrometry identified leukotriene B4 (LTB4) as the lipid mediator that was upregulated in the absence of MST1. We found that MST1 phosphorylated 5-lipoxygenase (5-LOX) at its T218 residue, disrupting the interaction between 5-LOX and 5-LOX-activating protein, resulting in a reduction of LTB4 production. In contrast, a 5-LOXT218A variant showed no response to MST1. Moreover, treatment of peritoneal macrophages with LTB4 or medium conditioned by Mst1-deficient macrophages resulted in high Ccl2 and Ccl4 expression and low Cxcl2 and Cd163 expression, except when the cells were co-treated with the LTB4 receptor 1 (BLT1) antagonist CP105696. Furthermore, CP105696 ameliorated cardiac dysfunction in LysMCre-mediated Mst1/2-deficient mice and enhanced cardiac repair in wild-type mice treated with XMU-MP-1 after MI. Conclusions: Taken together, our results demonstrate that inhibition of MST1/2 impaired post-MI repair through activating macrophage 5-LOX-LTB4-BLT1 axis.

8.
Ann Bot ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490877

RESUMO

BACKGROUND AND AIMS: Oilseed rape (Brassica napus) is one of the most important oil crops worldwide. Phosphorus (P) deficiency severely decreases the plant height (PH) and branch number (BN) of B. napus. However, the genetic bases controlling PH and BN in B. napus under P deficiency remain largely unknown. This study aims to mine candidate genes for PH and BN by genome-wide association study (GWAS) and determine low-P tolerance haplotypes. METHODS: An association panel of B. napus were grown in the field with a low P supply (P, 0 kg/ha) and a sufficient P supply (P, 40 kg/ha) across two years and PH and BN were investigated. More than five million single-nucleotide polymorphisms (SNPs) were used to conduct GWAS of PH and BN at two contrasting P supplies. KEY RESULTS: A total of 2127 SNPs were strongly associated (P < 6.25×10 -07) with PH and BN at two P supplies. There was significant correlation between phenotypic variation and the number of favorable alleles of associated loci on chromosomes A10 (chrA10_821671) and C08 (chrC08_27999846), which will contribute to breeding improvement by aggregating these SNPs. BnaA10g09290D and BnaC08g26640D were identified to be associated with the chrA10_821671 and chrC08_27999846, respectively. Candidate gene association analysis and haplotype analysis showed that the inbred lines carrying ATT at 'BnaA10g09290Hap1' and AAT at 'BnaC08g26640Hap1' had higher PH than lines carrying other haplotype alleles at low P supply. CONCLUSION: Our results demonstrate the power of GWAS in identifying genes of interest in B. napus and provided insights into the genetic basis of PH and BN at low P supply in B. napus. Candidate genes and favorable haplotypes may facilitate marker-based breeding efforts aimed at improving P use efficiency in B. napus.

9.
Small ; : e2102425, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494368

RESUMO

Designing highly efficient and durable electrocatalysts that accelerate sluggish oxygen reduction reaction kinetics for fuel cells and metal-air batteries are highly desirable but challenging. Herein, a facile yet robust strategy is reported to rationally design single iron active centers synergized with local S atoms in metal-organic frameworks derived from hierarchically porous carbon nanorods (Fe/N,S-HC). The cooperative trithiocyanuric acid-based coating not only introduces S atoms that regulate the coordination environment of the active centers, but also facilitates the formation of a hierarchically porous structure. Benefiting from electronic modulation and architectural functionality, Fe/N,S-HC catalyst shows markedly enhanced ORR performance with a half-wave potential (E1/2 ) of 0.912 V and satisfactory long-term durability in alkaline medium, outperforming those of commercial Pt/C. Impressively, Fe/N,S-HC-based Zn-air battery also presents outstanding battery performance and long-term stability. Both electrochemical experimental and density functional theoretical (DFT) calculated results suggest that the FeN4 sites tailored with local S atoms are favorable for the adsorption/desorption of oxygen intermediate, resulting in lower activation energy barrier and ultraefficient oxygen reduction catalytic activity. This work provides an atomic-level combined with porous morphological-level insights into oxygen reduction catalytic property, promoting rational design and development of novel highly efficient single-atom catalysts for the renewable energy applications.

10.
Arch Biochem Biophys ; 711: 109024, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34487720

RESUMO

This study attempted to determine the effect of EphA2 on H2O2-treated lens epithelial cells (SRA01/04) and the underlying mechanisms. MTT assay and flow cytometry were performed to assess cell viability and cell apoptosis. Western blot was carried out to examine the levels of proteins associated with apoptosis and autophagy. Our results revealed that EphA2 significantly elevated the reduced cell viability, and inhibited the increased cell apoptosis in H2O2-treated SRA01/04 cells, along with the significant up-regulated Bcl-2 and down-regulated Cleaved-caspase-3 and Bax protein levels, but which were all abolished by Rapa (autophagy activator). We also found that EphA2 significantly suppressed cell autophagy in H2O2-treated SRA01/04 cells. Additionally, EphA2 significantly up-regulated the protein levels of p-Akt and p-mTOR in H2O2-treated SRA01/04 cells, and the inhibition of Akt by MK-2206 and inhibition of mTOR by Rapa both obviously reversed EphA2-mediated the inhibition of autophagy in H2O2-treated SRA01/04 cells. In summary, these data demonstrated that EphA2 inhibited the apoptosis of SRA01/04 cells by inhibiting autophagy via activating PI3K/Akt/mTOR pathway.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34507896

RESUMO

BACKGROUND: Inflammation is often related to cancer, and several inflammatory scores have been established to predict the prognosis of various types of cancer. Our study aimed to determine the prognostic value of the preoperative lymphocyte to C-reactive protein ratio (LCR) for predicting postoperative outcomes in patients with resectable gallbladder cancer (GBC). METHODS: A retrospective analysis of 104 GBC patients who received curative surgery at Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine from January 2000 to December 2016 was performed. A time-dependent receiver operating characteristic curve was constructed to evaluate the accuracy of different markers. Univariate and multivariate Cox proportional hazard models were used to define factors associated with overall survival. RESULTS: Among the assessed variables, the preoperative LCR showed the highest accuracy in predicting the overall survival of GBC patients (AUC: 0.736). Decreased preoperative LCR was significantly associated with advanced tumor stage, including tumor invasion (P = 0.018), lymph node metastasis (P = 0.011) and TNM stage (P = 0.022). A low preoperative LCR (cutoff threshold = 145.5) was an independent risk factor for overall survival in patients with resectable GBC (P < 0.001). CONCLUSIONS: The preoperative LCR is a novel and valuable prognostic indicator of postoperative survival in patients with resectable GBC.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34508548

RESUMO

Bone marrow mesenchymal stromal cells (BMMSCs) are widely sourced and easily amplified in vitro; thus, they have a great potential in the treatment of hemopathies. Recent findings suggested that BMMSCs express the aryl hydrocarbon receptor (AHR). However, few studies have reported on the regulation of proliferative behaviors and metabolism by AHR in BMMSCs. In the present study, we found that activating AHR reduced the proliferation of BMMSCs and enhanced their mitochondrial function, whereas inhibiting AHR exerted the opposite effects. This study may provide the basis for further unveiling the molecular mechanisms and therapeutic potential of AHR in BMMSCs.

13.
Signal Transduct Target Ther ; 6(1): 339, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497264

RESUMO

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a global public burden on health authorities. Although the virological characteristics and pathogenesis of COVID-19 has been largely clarified, there is currently no specific therapeutic measure. In severe cases, acute SARS-CoV-2 infection leads to immune disorders and damage to both the adaptive and innate immune responses. Having roles in immune regulation and regeneration, mesenchymal stem cells (MSCs) serving as a therapeutic option may regulate the over-activated inflammatory response and promote recovery of lung damage. Since the outbreak of the COVID-19 pandemic, a series of MSC-therapy clinical trials has been conducted. The findings indicate that MSC treatment not only significantly reduces lung damage, but also improves patient recovery with safety and good immune tolerance. Herein, we summarize the recent progress in MSC therapy for COVID-19 and highlight the challenges in the field.

14.
J Biol Chem ; 297(3): 101036, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34343566

RESUMO

Proteins containing breast cancer type 1 (BRCA1) C-terminal domains play crucial roles in response to and repair of DNA damage. Epithelial cell transforming factor (epithelial cell transforming sequence 2 [ECT2]) is a member of the BRCA1 C-terminal protein family, but it is not known if ECT2 directly contributes to DNA repair. In this study, we report that ECT2 is recruited to DNA lesions in a poly (ADP-ribose) polymerase 1-dependent manner. Using co-immunoprecipitation analysis, we showed that ECT2 physically associates with KU70-KU80 and BRCA1, proteins involved in nonhomologous end joining and homologous recombination, respectively. ECT2 deficiency impairs the recruitment of KU70 and BRCA1 to DNA damage sites, resulting in defective DNA double-strand break repair, an accumulation of damaged DNA, and hypersensitivity of cells to genotoxic insults. Interestingly, we demonstrated that ECT2 promotes DNA repair and genome integrity largely independently of its canonical guanine nucleotide exchange activity. Together, these results suggest that ECT2 is directly involved in DNA double-strand break repair and is an important genome caretaker.

15.
Mol Med ; 27(1): 91, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412584

RESUMO

BACKGROUND: Intervertebral disc degeneration (IVDD) is the breakdown of the discs supporting the vertebrae. It is one of the most frequent causes of back pain worldwide. Currently, the clinical interventions for IVDD are mainly focused on symptom releases. Thus, new therapeutic options are needed. METHODS: Nucleus pulposus (NP) samples were obtained from 20 patients experiencing IVDD and 10 healthy volunteers compared for mRNA N6-methyladenosine (m6A) mRNA modification as well as methyltransferase (METT) like METTL3, METTL14, and Wilms' tumor 1-associated protein mRNA and protein abundance following exosomes exposure from mesenchymal stem cells. In addition, microRNA expressions were also compared. The correlation between the NLR family pyrin domain containing 3 (NLRP3) and METTL14 was measured by luciferase reporter assay. Cytokines were evaluated using an enzyme-linked immunosorbent assay. METTL14, NLRP3, and insulin-like growth factor 2 mRNA-binding protein 2 mRNAs were measured via a quantitative reverse transcription-polymerase chain reaction. Protein was assayed using western blots. Cell death was assessed by propidium iodide staining, lactate dehydrogenase release, gasdermin-N domain abundance, and caspase-1 activation. RESULTS: The human umbilical cord mesenchymal stem cell (hucMSC) exosomes were found to effectively improve the viability of NP cells and protect them from pyroptosis through targeting METTL14, with a methyltransferase catalyzing m6A modification. METTL14 was highly present in NP cells from IVDD patients, which stabilize NLRP3 mRNA in an IGFBP2-dependent manner. The elevated NLRP3 levels result in the increase of interleukin 1ß (IL-1ß) and IL-18 levels and trigger pyroptotic NP cell death. Such pathogenic axis could be blocked by hucMSC exosomes, which directly degrade METTL14 through exosomal miR-26a-5p. CONCLUSIONS: The results of the current study revealed the beneficial effects of hucMSC exosomes on NP cells and determined a potential mechanism inducing IVDD.

16.
Nat Commun ; 12(1): 4902, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385461

RESUMO

Efficient and precise base editors (BEs) for C-to-G transversion are highly desirable. However, the sequence context affecting editing outcome largely remains unclear. Here we report engineered C-to-G BEs of high efficiency and fidelity, with the sequence context predictable via machine-learning methods. By changing the species origin and relative position of uracil-DNA glycosylase and deaminase, together with codon optimization, we obtain optimized C-to-G BEs (OPTI-CGBEs) for efficient C-to-G transversion. The motif preference of OPTI-CGBEs for editing 100 endogenous sites is determined in HEK293T cells. Using a sgRNA library comprising 41,388 sequences, we develop a deep-learning model that accurately predicts the OPTI-CGBE editing outcome for targeted sites with specific sequence context. These OPTI-CGBEs are further shown to be capable of efficient base editing in mouse embryos for generating Tyr-edited offspring. Thus, these engineered CGBEs are useful for efficient and precise base editing, with outcome predictable based on sequence context of targeted sites.


Assuntos
Sistemas CRISPR-Cas , Citidina Desaminase/metabolismo , Edição de Genes/métodos , Aprendizado de Máquina , Uracila-DNA Glicosidase/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Caenorhabditis elegans/genética , Códon/genética , Citidina Desaminase/genética , Escherichia coli/genética , Feminino , Biblioteca Gênica , Células HEK293 , Humanos , Camundongos , Reprodutibilidade dos Testes , Uracila-DNA Glicosidase/genética
17.
J Pharmacol Toxicol Methods ; 112: 107108, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34363962

RESUMO

INTRODUCTION: Telemetered cynomolgus monkeys are widely used in cardiovascular toxicology research. However, the biological variations in their hemodynamics and electrocardiogram rhythms have not been fully elucidated. METHOD: To determine the potential effects of sex, handling stress, and circadian rhythm on the hemodynamics and electrocardiogram rhythms, data from 23 cynomolgus monkeys, implanted with DSI telemetry devices were examined. RESULTS: Our data showed that males had a longer RR interval (RRi), slower heart rate (HR), shorter QT and corrected QT intervals (QTc), and lower blood pressure than females. During the night time, the animals showed a longer RRi, PRi, QTi, and QTc; slower HR, and lower blood pressure. Handling stress at 0.25- to 1-h post-treatment caused a decrease in RRi and increase in HR and QTi. For RRi, HR, and systolic, diastolic, and mean blood pressure, the coefficients of variation (CVs) between studies of individual animals were less than 30%; for other parameters, the CVs were less than 20%. DISCUSSION: We demonstrated that sex, circadian rhythms, and handling stress all contributed towards variations in telemetry data, albeit to different extents. For each individual animal, the biological variation across different studies was relatively small and acceptable.

18.
Trials ; 22(1): 545, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407832

RESUMO

BACKGROUND: Proton pump inhibitor (PPI) is effective for the treatment of nonerosive gastroesophageal reflux (NERD), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, and clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites. METHODS: This is a single-center, randomized controlled, double-blind, placebo-controlled clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with omeprazole enteric-coated tablets placebo, while the western medicine group will receive omeprazole enteric-coated tablets with HWJNR placebo. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health-related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of life scale (SF-36), patient-reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively. DISCUSSION: The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabolomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR. ChiCTR2000041225 . Registered on 22 December 2020.


Assuntos
Medicamentos de Ervas Chinesas , Qualidade de Vida , China , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Temperatura Alta , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
19.
Huan Jing Ke Xue ; 42(9): 4319-4331, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414730

RESUMO

Dissolved organic matter (DOM) plays an important role in the evolution of microbial communities. Meanwhile, ecological water delivery is an important feature of Baiyangdian Lake. To explore how the structure of the aerobic denitrification bacteria community responds to DOM during the water delivery period, the DOM components of water were examined and high-throughput sequencing of aerobic denitrification bacteria was performed. The results showed significant differences in DOM concentration in Baiyangdian Lake, with the estuary area exhibiting lower DOM concentrations. The water exhibited strong autogenous source, while DOM in the estuary area had a higher molecular weight and degree of humification. Three protein-like substances (C1, C2, and C4) and one humic-like substance (C3) were identified through PARAFAC. The protein-like substances accounted for the major proportion of DOM, which was consistent with the results of fluorescence regional integration (FRI). The genera of the water body were mainly in the Protebacterice phylum, including Cupriavidus, Aeromonas, Thauera, Shewanella, and Pseudomonas. Meanwhile, Cupriavidus, Thauera, Shewanella, Agrobacterium, and Pseudomonas were the main indicator species, according to random forest (RF) analysis. Through network analysis, 35 key nodes of the network were obtained, belonging to Thauera, Cupriavidus, and Unclassified_bacteria, respectively. Redundancy analysis (RDA) showed that a humic-like substance was the main environmental factor regulating the whole structure of the aerobic denitrification bacterial community, while protein-like substances played important roles in changes to the indicator species and key nodes of the community. Overall, protein-like substances could provide an important reference for selecting carbon sources during the screening of efficient and cold resistance aerobic denitrification bacteria that are adapted to actual water bodies.


Assuntos
Desnitrificação , Lagos , Bactérias/genética , Estuários , Água
20.
Nat Commun ; 12(1): 5058, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433808

RESUMO

Dietary interventions such as intermittent fasting (IF) have emerged as an attractive strategy for cancer therapies; therefore, understanding the underlying molecular mechanisms is pivotal. Here, we find SIRT7 decline markedly attenuates the anti-tumor effect of IF. Mechanistically, AMP-activated protein kinase (AMPK) phosphorylating SIRT7 at T263 triggers further phosphorylation at T255/S259 by glycogen synthase kinase 3ß (GSK3ß), which stabilizes SIRT7 by decoupling E3 ligase UBR5. SIRT7 hyperphosphorylation achieves anti-tumor activity by disrupting the SKP2-SCF E3 ligase, thus preventing SKP2-mediated K63-linked AKT polyubiquitination and subsequent activation. In contrast, GSK3ß-SIRT7 axis is inhibited by EGF/ERK2 signaling, with ERK2 inactivating GSK3ß, thus accelerating SIRT7 degradation. Unfavorably, glucose deprivation or chemotherapy hijacks the GSK3ß-SIRT7 axis via ERK2, thus activating AKT and ensuring survival. Notably, Trametinib, an FDA-approved MEK inhibitor, enhances the efficacy of combination therapy with doxorubicin and IF. Overall, we have revealed the GSK3ß-SIRT7 axis that must be fine-tuned in the face of the energetic and oncogenic stresses in malignancy.

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