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1.
Zhongguo Zhen Jiu ; 41(9): 1023-8, 2021 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-34491653

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of interleukin (IL) -23/IL-17 axis and Toll-like receptor 4 (TLR4) in the infarcted tissue in rats with myocardial infarction (MI), and to explore the mechanism of EA on alleviating MI injury. METHODS: Forty male SD rats were randomly divided into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The MI models were established by ligation of left anterior descending coronary artery in the model group and EA group, while only threading was performed in the sham-operation group and sham-operation plus EA group. The rats in the sham-operation plus EA group and EA group were treated with EA at "Neiguan" (PC 6), disperse-dense wave, 2 Hz/100 Hz, 2 mA, once a day, 20 min each time, for 3 days. After the intervention, the ejection fraction (EF) was measured by echocardiography to evaluate the cardiac function; the infarct area was measured by TTC staining; the HE staining was used to observe the morphological changes of myocardial tissue; the levels of IL-23 and IL-17 in infarcted tissue were detected by ELISA; the protein expression of TLR4 in infarcted tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the EF was decreased (P<0.01), the infarct area was increased (P<0.01), the myocardial fiber injury was obvious, accompanied by inflammatory cell infiltration, and the contents of IL-23, IL-17 and the expression of TLR4 in infarcted tissue were increased in the model group (P<0.01). Compared with the model group, the EF was increased (P<0.05), the infarct area was reduced (P<0.05), the myocardial fiber injury was significantly improved, the inflammatory cell infiltration was reduced, and the contents of IL-23, IL-17 and TLR4 expression in infarcted tissue were decreased in the EA group (P<0.05). CONCLUSION: EA may alleviate the excessive inflammatory response after MI by inhibiting the expression of IL-23/IL-17 axis in MI rats, and TLR4 may be involved during the process.


Assuntos
Eletroacupuntura , Infarto do Miocárdio , Animais , Interleucina-17/genética , Interleucina-23/genética , Masculino , Infarto do Miocárdio/genética , Infarto do Miocárdio/terapia , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/genética
2.
Environ Technol ; : 1-9, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34516343

RESUMO

Ammonia (NH3) stripping by microwave irradiation was used to increase the efficiency of anaerobic digestion. The effects of final temperature (FT) (80 ≤ FT ≤ 100°C) and microwave irradiation time (MIT) (2.5 ≤ MIT ≤ 5.5 min) of NH3 stripping, and hydraulic retention time (HRT) (7 ≤ HRT ≤ 20 d) in anaerobic digester were quantified. NH3 concentration decreased from 2794 to 140 mg/L within 5.5 min at FT = 100°C. The highest cumulative biogas production (>1800 mL/L) and efficiency of volatile solid removal (> 68%) were achieved at FT = 100°C and MIT = 5.5 min. The removal efficiency of volatile solid in digesters fed with untreated swine wastewater (control) and swine wastewater treated by NH3 stripping decreased as HRT decreased. The highest relative improvement of properties compared to the control occurred at 10 or 15 d HRT. Increases in biogas production compared to the control increased with the NH3 stripping as HRT was reduced to 10 d (243% higher at 10 d). The methane content of the produced biogas was 64-69% for control and 68-75% with NH3 stripping in the range of 10-20 d HRT. NH3 stripping using microwave irradiation is an effective pretreatment to improve the anaerobic digestion of swine wastewater.

3.
Nat Commun ; 12(1): 5672, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34584078

RESUMO

Nature forms S-S bonds by oxidizing two sulfhydryl groups, and no enzyme installing an intact hydropersulfide (-SSH) group into a natural product has been identified to date. The leinamycin (LNM) family of natural products features intact S-S bonds, and previously we reported an SH domain (LnmJ-SH) within the LNM hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line as a cysteine lyase that plays a role in sulfur incorporation. Here we report the characterization of an S-adenosyl methionine (SAM)-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin (GNM) biosynthesis, discovery of hydropersulfides as the nascent products of the GNM and LNM hybrid NRPS-PKS assembly lines, and revelation of three SH domains (GnmT-SH, LnmJ-SH, and WsmR-SH) within the GNM, LNM, and weishanmycin (WSM) hybrid NRPS-PKS assembly lines as thiocysteine lyases. Based on these findings, we propose a biosynthetic model for the LNM family of natural products, featuring thiocysteine lyases as PKS domains that directly install a -SSH group into the GNM, LNM, or WSM polyketide scaffold. Genome mining reveals that SH domains are widespread in Nature, extending beyond the LNM family of natural products. The SH domains could also be leveraged as biocatalysts to install an -SSH group into other biologically relevant scaffolds.

4.
Cancer Lett ; 520: 295-306, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389433

RESUMO

Interleukin (IL-6) is a pleotropic cytokine with both tumor-promoting and -inhibitory effects on breast cancer growth. However, the mechanisms governing the outcome of IL-6 on cancer progression remain to be clarified. Our study unraveled a novel long noncoding RNA (lncRNA) AU021063 downstream of IL-6 signaling. We found that IL-6 induced the expression of AU021063 predominantly in breast cancer compared to other cancer types. Mechanistically, IL-6 induced AT-rich interactive domain 5a (Arid5a) expression, which promotes the transcription of AU021063. In turn, AU021063 promotes breast cancer metastasis through stabilizing tribbles homolog 3 (Trib3) and activating Mek/Erk signaling pathway. Genetic ablation of either Arid5a, AU021063 or Trib3 abolished breast cancer metastasis in vitro and in vivo. Overall, our study highlights the importance of IL-6-Arid5a-AU021063 axis in regulating breast cancer invasiveness and metastasis, which may provide potential novel therapeutics for breast cancer.

5.
Microvasc Res ; 138: 104235, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34453991

RESUMO

Electroacupuncture (EA) intervention has a remarkable cardioprotection against myocardial ischemia reperfusion injury (MIRI). Recently, it has been suggested that the gut microbiota plays an important role in regulating the progression and prognosis of MIRI. The purpose of this study was to illustrate the relationship between gut microbiota and cardioprotection of EA on MIRI. We conducted a MIRI model by ligating the left anterior descending coronary artery for 30 min followed by reperfusion in male Sprague Dawley rats, which then received 7 days of EA intervention. Echocardiography was employed to evaluate left ventricular function. Fecal samples were collected for microbial analysis by 16S rDNA high-throughput sequencing. Blood samples and myocardium were collected for inflammatory cytokine detection by enzyme linked immunosorbent assay (ELISA) and Western blot. Hematoxylin & eosin (HE) staining and immunofluorescence of ileum tissue were performed for intestinal damage evaluation. After 7 days of EA intervention, the left ventricular function was improved with significantly increased ejection fraction and fractional shortening. Furthermore, we found that EA intervention reversed the changed gut microbiota induced by MIRI, including Clostridiales, RF39, S24-7, Desulfovibrio, and Allobaculum, improved the impaired gut barrier, reduced the production and circulation of lipopolysaccharide (LPS), inhibited the level of interleukin 6 (IL-6) and interleukin 12 (IL-12) in periphery and decreased the expression of Toll like receptor 4 (TLR4) and IL-6 in myocardium. EA intervention could improve the impaired gut mucosal barrier and reduce the production and circulation of LPS after MIRI through regulating gut microbiota, thus inhibiting the circulation and myocardium inflammation and finally exerted the cardioprotective effect.

6.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207373

RESUMO

A nucleic acid aptamer that specifically recognizes methicillin-resistant Staphylococcus aureus (MRSA) has been immobilized on magnetic nanoparticles to capture the target bacteria prior to mass spectrometry analysis. After the MRSA species were captured, they were further eluted from the nanoparticles and identified using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The combination of aptamer-based capture/enrichment and MS analysis of microorganisms took advantage of the selectivity of both techniques and should enhance the accuracy of MRSA identification. The capture and elution efficiencies for MRSA were optimized by examining factors such as incubation time, temperature, and elution solvents. The aptamer-modified magnetic nanoparticles showed a capture rate of more than 90% under the optimized condition, whereas the capture rates were less than 11% for non-target bacteria. The as-prepared nanoparticles exhibited only a 5% decrease in the capture rate and a 9% decrease in the elution rate after 10 successive cycles of utilization. Most importantly, the aptamer-modified nanoparticles revealed an excellent selectivity towards MRSA in bacterial mixtures. The capture of MRSA at a concentration of 102 CFU/mL remained at a good percentage of 82% even when the other two species were at 104 times higher concentration (106 CFU/mL). Further, the eluted MRSA bacteria were successfully identified using MALDI mass spectrometry.


Assuntos
Aptâmeros de Nucleotídeos/química , Nanopartículas de Magnetita/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Staphylococcus aureus Resistente à Meticilina/citologia , Técnica de Seleção de Aptâmeros/métodos
7.
Photochem Photobiol Sci ; 20(5): 627-637, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33913116

RESUMO

Low-molecular-weight (MW) polyols are organic osmolytes influencing water activity. We have investigated the effects of polyol molecules (glycerol and sorbitol) on the optical and triplet excitation dynamics of light-harvesting complex 2 (LH2) from Rhodobacter (Rba.) sphaeroides in buffer-detergent solutions. The resonance Raman spectroscopy demonstrated that, on increasing glycerol and sorbitol volume fractions ranging from 0 to 80% (v/v) (accompanied by the decreasing water activities), the planar and all-trans conformation of carotenoids (Crts) remained unchanged, and the bacteriochlorophyll a (BChl) Qy absorption intensity decreased. The B850 fluorescence amplitude elevated in the 20-80% v/v sorbitol and 20-40% v/v glycerol solution, but decreased in 80% v/v glycerol solution. The change of 3[Crt*-BChl] interaction bands caused by 3Crt*-BChl interaction had no obvious correlation with water activities against polyol volume fractions, which are rationalized by the water activity sensitive of C- and N-termini of protein which binding with BChls. The results suggest that Rba. sphaeroides LH2 is more sensitive to low-molecular-weight polyols compared with that of the thermophiles purple bacterium Thermochromatium (Tch.) tepidum we had investigated before.

8.
Pediatr Neonatol ; 62(3): 292-297, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33714703

RESUMO

BACKGROUND: Complications of percutaneous central venous catheters (PCVCs) include catheter-related blood stream infection (CRBSI), occlusion, leakage, and phlebitis, which may lead to sepsis or prolonged hospitalization. The primary objective of this randomized controlled trial was to determine the appropriate frequency of dressing for percutaneous central venous catheters in preventing CRBSI, every week regularly vs. non-regularly, in premature neonates in NICU. METHODS: Patients in NICU requiring PCVCs from March 2019-May 2020 were enrolled. Enrolled patients were randomly assigned into 2 groups: regular dressing group (RD), for which dressings were changed every week regularly, or additionally when oozing was noticed; and non-regular dressing group (ND), for which dressings were changed only when oozing was visible. The incidence of CRBSI, occlusion, leakage, and phlebitis were compared between the two groups using the Chi-squared test. The incidence of catheter-related complications was defined as numbers of episodes per 1000 catheter-days. RESULTS: A total of 197 PCVCs were enrolled. The ND and RD groups had 99 and 98 PCVCs, respectively. The average CD interval was 9.3 days in ND group and 5.8 days in RD group. The incidence of CRBSI in RD group was 0‰, which was significantly lower than that of ND group, which was 2.0‰ (p = 0.048), but no significant differences were found between groups in the incidence of occlusion, leakage, and phlebitis of PCVCs. CONCLUSION: Regular dressing changes every week and when oozing occurs while maintaining the protocol of maximum sterile barrier precautions is the best method and frequency of dressings of PCVCs.

9.
Biochim Biophys Acta Gen Subj ; 1865(6): 129859, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33581251

RESUMO

BACKGROUND: Giardia lamblia differentiates into resistant cysts as an established model for dormancy. Myeloid leukemia factor (MLF) proteins are important regulators of cell differentiation. Giardia possesses a MLF homolog which was up-regulated during encystation and localized to unknown cytosolic vesicles named MLF vesicles (MLFVs). METHODS: We used double staining for visualization of potential factors with role in protein metabolism pathway and a strategy that employed a deletion mutant, CDK2m3, to test the protein degradation pathway. We also explored whether autophagy or proteasomal degradation are regulators of Giardia encystation by treatment with MG132, rapamycin, or chloroquine. RESULTS: Double staining of MLF and ISCU or CWP1 revealed no overlap between their vesicles. The aberrant CDK2m3 colocalized with MLFVs and formed complexes with MLF. MG132 increased the number of CDK2m3-localized vesicles and its protein level. We further found that MLF colocalized and interacted with a FYVE protein and an ATG8-like (ATG8L) protein, which were up-regulated during encystation and their expression induced Giardia encystation. The addition of MG132, rapamycin, or chloroquine, increased their levels and the number of their vesicles, and inhibited the cyst formation. MLF and FYVE were detected in exosomes released from culture. CONCLUSIONS: The MLFVs are not mitosomes or encystation-specific vesicles, but are related with degradative pathway for CDK2m3. MLF, FYVE, and ATG8L play a positive role in encystation and function in protein clearance pathway, which is important for encystation and coordinated with Exosomes. GENERAL SIGNIFICANCE: MLF, FYVE, and ATG8L may be involved an encystation-induced protein metabolism during Giardia differentiation.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Cistos/patologia , Giardia lamblia/metabolismo , Encistamento de Parasitas , Proteínas de Protozoários/metabolismo , Proteínas de Ciclo Celular/genética , Quinase 2 Dependente de Ciclina/genética , Cistos/metabolismo , Giardia lamblia/genética , Giardia lamblia/crescimento & desenvolvimento , Proteínas de Protozoários/genética
10.
Pediatr Neonatol ; 62(3): 265-270, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33637475

RESUMO

BACKGROUND: Percutaneous central venous catheters (PCVCs) are used commonly and widely in the neonatal intensive care unit (NICU). Malposition of PCVCs may cause life-threatening complications and prolong hospitalization. In Taiwan, conventional chest-abdomen radiography (CXR) has been used widely and routinely for assessing tip location of PCVCs. Compared to ultrasonography (US), CXR cannot provide real-time assessment, and patients are exposed to radiation. Therefore, this study aimed to analyze the role of US in detecting PCVC tip location in the lower extremities. METHODS: Neonates who received PCVC insertion in the lower extremities in NICU from March 2019 to April 2020 were enrolled in this prospective cohort study. PCVC tip location was confirmed finally by conventional CXR after US examination and patients were included in the sono group; those not assessed by US formed the non-sono group. In addition, PCVCs inserted in 2018 for which tip location was evaluated only by CXR, were reviewed retrospectively and these cases were included in the non-sono group. Withdrawal rates between the two groups were analyzed using Chi-square test. RESULTS: The sono group included 166 neonates with PCVCs and 141 were in the non-sono group. Median gestational age at date of PCVC insertion was 33.21 and 32.71 weeks in sono and non-sono groups, respectively (p = 0.37). Withdrawal rates were 10.84% and 65.95% (p < 0.001) and duration for catheter location confirmation were 2-4.75 min and 75-247.25 min (p < 0.001), respectively. CONCLUSION: US provides more reliable images than conventional radiography alone for identifying PCVC tip locations in the lower extremities. It can effectively reduce catheter insertion duration, and was associated with fewer manipulations.

11.
Zhen Ci Yan Jiu ; 46(1): 58-63, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33559427

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture(EA)pretreatment on transient receptor potential vanilloid 1(TRPV1)/calcitonin gene-related peptide(CGRP)signal and nuclear factor-κB p65 (NF-κB p65) protein expression in myocardial tissue of acute myocardial ischemic injury (AMI) rats, and to investigate the possible mechanism of electroacupuncture pretreatment against AMI. METHODS: A total of 60 adult male SD rats were randomly divided into blank control, sham operation, model and EA pretreatment groups, 15 rats in each group. The acute myocardial ischemia model was established by ligating the left anterior descending (LAD)branch of the coronary artery in the model group and EA pretreatment group, while threading but no ligating at left anterior descending branch of the coronary artery was applied in the sham operation group. In the EA pretreatment group, bilateral "Neiguan"(PC6) acupoints were selected, with intensity of 2 mA and frequency of 2 Hz/100 Hz, for 20 min, once daily for 7 days before modeling. Electrocardiogram (ECG) was recorded by physiological signal acquisition system, and the ST segment potential offset values of standard Ⅱ lead were analyzed before surgery,30 min and 24 h after operation. The TTC staining was used to observe the percentage of myocardial infarction area. The HE staining was used to observe the pathological changes of myocardial tissue and the degree of inflammatory cell infiltration. And Western blot was used to detect TRPV1/CGRP signal and NF-κB p65 protein expression levels in myocardial tissue. RESULTS: Compared with the sham operation group, the ECG-J point potential in the model group was significantly increased at 30 min and decreased at 24 h after operation (P<0.05), myocardial infarction area increased significantly (P<0.05), the myocardial fibers were obviously disordered, inflammatory cell infiltration was obvious, and the expressions of TRPV1,CGRP and NF-κB p65 proteins were all increased (P<0.05). Compared with the model group, the EA pretreatment group was decreased in the ECG-J point potential at 30 min after operation(P<0.05), significantly reduced in myocardial infarction area (P<0.05), improved in the morphology of myocardial fibers, reduced ininflammatory cell infiltration, and increased in the protein expressions of TRPV1 and CGRP in myocardium (P<0.05), significantly decreased in the protein expression of NF-κB p65 (P<0.05). CONCLUSION: EA pretreatment may enhance TRPV1/CGRP signaling, down-regulate NF-κB p65 protein expression, reduce myocardial inflammatory response status, improve AMI injury, and reduce myocardial infarction area.


Assuntos
Eletroacupuntura , Isquemia Miocárdica , Pontos de Acupuntura , Animais , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina/genética , Masculino , Isquemia Miocárdica/genética , Isquemia Miocárdica/terapia , NF-kappa B/genética , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV/genética
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 9-16, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554790

RESUMO

OBJECTIVE: To analyze the relationship between the expression level of SQLE and the prognosis of patients with acute myeloid leukemia (AML) through large sample data. METHODS: The data of genome, transcriptome, gene chip expression, and clinical information were statistically analyzed in multiple cohorts of AML patients with large samples. RESULTS: It was found that the expression level of SQLE gene in tumor cells of AML patients was significantly higher than that of healthy controls (P=0.001). In the three AML corhort, the SQLE high expression group showed a worse therapeutic outcome (OS, P=0.009, P=0.0001, P=0.006; EFS, P=0.005, P=0.001). The unvariate and multivariate survival prognosis analysis indicated that the high expression of SQLE suggests lower event-free survival rate (EFS, HR=1.551, P<0.05) and overall survival rate (OS, HR=1.484, P<0.05). At the same time, it was also found that among different risk subgroups, the expression of SQLE in high risk group was higher (P<0.001, P=0.01), while the patients with high SQLE expression, who received allogeneic HSCT, had longer overall survival time (P=0.006). CONCLUSION: The up-regulation SQLE expression suggests a poor prognosis for the patients with AML.


Assuntos
Leucemia Mieloide Aguda , Intervalo Livre de Doença , Humanos , Prognóstico , Taxa de Sobrevida , Transcriptoma
13.
Angew Chem Int Ed Engl ; 60(13): 7140-7147, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33465268

RESUMO

Sulfur incorporation into natural products is a critical area of biosynthetic studies. Recently, a subset of sulfur-containing angucyclines has been discovered, and yet, the sulfur incorporation step is poorly understood. In this work, a series of thioether-bridged angucyclines were discovered, and a cryptic epoxide Michael acceptor intermediate was revealed en route to thioangucyclines (TACs) A and B. However, systematic gene deletion of the biosynthetic gene cluster (BGC) by CRISPR/Cas9 could not identify any gene responsible for the conversion of the epoxide intermediate to TACs. Instead, a series of in vitro and in vivo experiments conclusively showed that the conversion is the result of two non-enzymatic steps, possibly mediated by endogenous hydrogen sulfide. Therefore, the TACs are proposed to derive from a detoxification process. These results are expected to contribute to the study of both angucyclines and the utilization of inorganic sulfur in natural product biosynthesis.


Assuntos
Antraquinonas/metabolismo , Compostos de Sulfidrila/metabolismo , Enxofre/metabolismo , Antraquinonas/química , Conformação Molecular , Compostos de Sulfidrila/química , Enxofre/química
14.
J Adv Nurs ; 77(6): 2565-2580, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33450107

RESUMO

AIMS: To evaluate the effects of mindfulness-based intervention on psychotic symptoms, positive symptoms, negative symptoms, depressive symptoms, anxiety, and rehospitalization. DESIGN: A meta-analysis of randomized controlled trials. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, National Digital Library of Theses and Dissertations in Taiwan, and Airiti Library were searched from their earliest available date up to April 2019. REVIEW METHODS: The guidelines of the Cochrane Collaboration were followed to report this systematic review. Two authors conducted this meta-analysis independently. RESULTS: Nine randomized controlled trials were included. Meta-analysis showed that mindfulness-based intervention significantly decreased psychotic symptoms, positive symptoms, negative symptoms, depressive symptoms, and duration of rehospitalization among patients with schizophrenia, and that the reduction in negative symptoms lasted through short-term follow-up. The moderation analysis showed that significantly decreased positive symptoms occurred in the nurse-led intervention group, while no significant impact was found in the psychologist-led intervention group. CONCLUSION: The psychotic symptoms of the patients with schizophrenia are improved after mindfulness-based intervention and the effects on the negative symptoms can be maintained for at least 3 to 6 months. Mindfulness-based intervention provided by nurses produces more improvements in positive symptoms than intervention provided by psychologists. IMPACT: A growing number of mindfulness-based interventions have been implemented for patients with schizophrenia, although the effectiveness had not previously been established by meta-analysis. Mindfulness-based interventions appear to reduce the symptom severity of schizophrenia patients. Further suggestions for healthcare providers and researchers are provided and discussed.


Assuntos
Atenção Plena , Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/terapia , Taiwan
15.
Arch Biochem Biophys ; 697: 108720, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33307065

RESUMO

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is closely related to cardiomyocyte apoptosis. Stimulating ß2 adrenergic receptor (ß2AR) can effectively combat cardiomyocyte apoptosis. Previous studies demonstrate that the gut microbial metabolite phenylacetylglycine (PAGly) can stimulate ß2AR. However, the effect of PAGly on myocardial I/R injury remains unknown. METHODS: The hypoxia/reoxygenation (H/R) model was established using the neonatal mouse cardiomyocytes (NMCMs). Different doses of PAGly were used to treat NMCMs, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Additionally, the level of cyclic adenosine monophosphate (cAMP) was examined by using a cAMP detection kit. Mouse model of myocardial I/R injury was established in C57BL/6 mice, and different doses of phenylacetic acid were administrated intraperitoneally. Apoptosis of myocardial cells was detected by TUNEL and α-actin staining. The area at risk and the infarct areas were identified by 2,3,5-triphenyltetrazolium chloride (TTC) and Evans blue staining. Western blotting was used to measure the protein expression levels of phosphorylated phosphatidylinositol 3-kinase (p-PI3K), total Akt (t-Akt), phosphorylated Akt (p-AKT), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cleaved caspase-3. RESULTS: PAGly significantly suppressed H/R injury-induced apoptosis in NMCMs and inhibited apoptosis in myocardial I/R injured mice in vivo. We verified that PAGly activated the anti-apoptotic Gαi/PI3K/AKT signaling cascade in NMCMs via stimulating ß2AR signaling. Continuous administration of PAGly at an appropriate dose could inhibit apoptosis and reduce the infarct size resulting from I/R injury in mice. However, high-dose PAGly treatment was associated with a higher mortality rate. Moreover, we demonstrated that Aspirin reduced the infarct size and the high mortality caused by high doses of PAGly in I/R injured mice. CONCLUSIONS: These findings suggest that treatment with the gut microbial metabolite PAGly could suppress cardiomyocyte apoptosis caused by myocardial I/R injury and reduce the infarct size, which provides a novel therapeutic strategy for patients with myocardial infarction.


Assuntos
Microbioma Gastrointestinal , Glicina/análogos & derivados , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Receptores Adrenérgicos beta 2/metabolismo , Animais , Citoproteção/efeitos dos fármacos , Glicina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/patologia
16.
ACS Chem Biol ; 16(1): 96-105, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33314918

RESUMO

The members of the arylamine N-acetyltransferase (NAT) family of enzymes are important for their many roles in xenobiotic detoxification in bacteria and humans. However, very little is known about their roles outside of detoxification or their specificities for acyl donors larger than acetyl-CoA. Herein, we report the detailed study of PtmC, an unusual NAT homologue encoded in the biosynthetic gene cluster for thioplatensimycin, thioplatencin, and a newly reported scaffold, thioplatensilin, thioacid-containing diterpenoids and highly potent inhibitors of bacterial and mammalian fatty acid synthases. As the final enzyme of the pathway, PtmC is responsible for the selection of a thioacid arylamine over its cognate carboxylic acid and coupling to at least three large, 17-carbon ketolide-CoA substrates. Therefore, this study uses a combined approach of enzymology and molecular modeling to reveal how PtmC has evolved from the canonical NAT scaffold into a key part of a natural combinatorial biosynthetic pathway. Additionally, genome mining has revealed the presence of other related NATs located within natural product biosynthetic gene clusters. Thus, findings from this study are expected to expand our knowledge of how enzymes evolve for expanded substrate diversity and enable additional predictions about the activities of NATs involved in natural product biosynthesis and xenobiotic detoxification.


Assuntos
Acetiltransferases/metabolismo , Xenobióticos/metabolismo , Catálise , Genes Bacterianos , Streptomyces/genética , Streptomyces/metabolismo , Especificidade por Substrato
17.
J Exp Clin Cancer Res ; 39(1): 278, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298132

RESUMO

BACKGROUND: Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. METHODS: In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. RESULTS: Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

18.
Adv Mater ; : e2007264, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33336516

RESUMO

Multiferroics-materials that exhibit coupled ferroic orders-are considered to be one of the most promising candidate material systems for next-generation spintronics, memory, low-power nanoelectronics and so on. To advance potential applications, approaches that lead to persistent and extremely fast functional property changes are in demand. Herein, it is revealed that the phase transition and the correlated ferroic orders in multiferroic BiFeO3 (BFO) can be modulated via illumination of single short/ultrashort light pulses. Heat transport simulations and ultrafast optical pump-probe spectroscopy reveal that the transient strain induced by light pulses plays a key role in determining the persistent final states. Having identified the diffusionless phase transformation features via scanning transmission electron microscopy, sequential laser pulse illumination is further demonstrated to perform large-area phase and domain manipulation in a deterministic way. The work contributes to all-optical and rapid nonvolatile control of multiferroicity, offering different routes while designing novel optoelectronics.

19.
Int J Biol Sci ; 16(13): 2283-2295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760197

RESUMO

Liver diseases are one of the leading causes of mortality in the world, mainly caused by different etiological agents, alcohol consumption, viruses, drug intoxication, and malnutrition. The maturation of gene therapy has heralded new avenues for developing effective interventions for these diseases. Derived from a remarkable microbial defense system, clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins 9 system (CRISPR/Cas9 system) is driving innovative applications from basic biology to biotechnology and medicine. Recently, the mutagenic function of CRISPR/Cas9 system has been widely adopted for genome and disease research. In this review, we describe the development and applications of CRISPR/Cas9 system on liver diseases for research or translational applications, while highlighting challenges as well as future avenues for innovation.

20.
Nanoscale Res Lett ; 15(1): 172, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32857192

RESUMO

Researchers have long been seeking multifunctional materials that can be adopted for next-generation nanoelectronics, and which, hopefully, are compatible with current semiconductor processing for further integration. Along this vein, complex oxides have gained numerous attention due to their versatile functionalities. Despite the fact that unbounded potential of complex oxides has been examined over the past years, one of the major challenges lies in the direct integration of these functional oxides onto existing devices or targeted substrates that are inherently incompatible in terms of oxide growth. To fulfill this goal, freestanding processes have been proposed, in which wet etching of inserted sacrificial layers is regarded as one of the most efficient ways to obtain epitaxial high-quality thin films. In this study, we propose using an alternative oxide, YBa2Cu3O7 (YCBO), as a sacrificial layer, which can be easily dissolved in light hydrochloric acid in a more efficient way, while protecting selected complex oxides intact. The high epitaxial quality of the selected complex oxide before and after freestanding process using YBCO as a sacrificial layer is comprehensively studied via a combination of atomic force microscopy, X-ray diffraction, transmission electron microscopy, and electrical transports. This approach enables direct integration of complex oxides with arbitrary substrates and devices and is expected to offer a faster route towards the development of low-dimensional quantum materials.

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