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1.
Macromol Biosci ; : e2000116, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32603032

RESUMO

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) for relieving inflammatory reactions can lead to severe side effects. It is of great importance to configure new dosing strategies for alleviating the side effects of NSAIDs. In this work, an enzyme-responsive anti-inflammatory prodrug capable of generating indomethacin upon the trigger of inflammation is developed. A monomer is first prepared after the esterification of carboxyl groups of indomethacin by hydroxyl groups of N-(2-hydroxyethyl) acrylamide. Then, a polymer prodrug, with indomethacin linked through ester bonds on the side chain, is synthesized by free radical polymerization of the monomer. The therapeutic drug component can be triggered to release from the prodrug under the stimulation of cholesterol esterase, mimicking the inflammation environment. On the contrary, there is only a small amount of drug released in the absence of the enzyme. Therefore, the drug can be triggered to release under the stimulation of an environment mimicking inflammation. Furthermore, the in vitro studies at the cellular level indicate that the enzyme-responsive prodrug can efficiently relieve inflammatory responses induced by lipopolysaccharide in RAW264.7 macrophage cells while indicating no cytotoxicity.

2.
Pharm Stat ; 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32537913

RESUMO

It is well recognized that cancer drug development for children and adolescents has many challenges, from biological and societal to economic. Pediatric cancer consists of a diverse group of rare diseases, and the relatively small population of children with multiple, disparate tumor types across various age groups presents a significant challenge for drug development programs as compared to oncology drug development programs for adults. Due to the different types of cancers, limited opportunities exist for extrapolation of efficacy from adult cancer indications to children. Thus, innovative study designs including Bayesian statistical approaches should be considered. A Bayesian approach can be a flexible tool to formally leverage prior knowledge of adult or external controls in pediatric cancer trials. In this article, we provide in a case example of how Bayesian approaches can be used to design, monitor, and analyze pediatric trials. Particularly, Bayesian sequential monitoring can be useful to monitor pediatric trial results as data accumulate. In addition, designing a pediatric trial with both skeptical and enthusiastic priors with Bayesian sequential monitoring can be an efficient mechanism for early trial cessation for both efficacy and futility. The interpretation of efficacy using a Bayesian approach is based on posterior probability and is intuitive and interpretable for patients, parents and prescribers given limited data.

3.
Complement Med Res ; : 1-5, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32464629

RESUMO

INTRODUCTION: The aim of this research was to assess the safety and effectiveness of traditional Chinese Eight Brocade exercise for ankylosing spondylitis (AS). METHODS: A literature search was conducted using twelve databases (Web of Science, EBSCO, AMED, SCOPUS, CINAHL, MEDLINE, EMBASE, DBPIA, KoreaMed Synapse, Oriental Medicine Advanced Searching Integrated System, Chinese Wan Fang, and China National Knowledge Infrastructure) from inception to June 2019. We only included randomized controlled trials (RCTs) regarding traditional Chinese Eight Brocade exercise for AS. For statistical analysis, we adopted a quantitative analysis using the RevMan 5.3 statistical software. RESULTS: Five eligible RCTs involving 308 participants were included in the systematic review. The meta-analysis showed superior effects of traditional Chinese Eight Brocade exercise plus NSAIDs therapy on response rate, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), inflammatory indicators, and bone mineral density when compared with NSAIDs therapy alone (p < 0.05). Moreover, when used alone, traditional Chinese Eight Brocade exercise significantly improved fatigue, intensity of morning stiffness domains, and duration of morning stiffness domains of BASDAI scores in comparison to waiting list controls (p < 0.05). CONCLUSION: Traditional Chinese Eight Brocade exercise could improve physical function and reduce disease activity and inflammatory indicators in AS patients. However, the level of evidence was low because of the high risk of bias. Further rigorously designed RCTs are warranted before it can be recommended.

4.
Aging (Albany NY) ; 12(9): 8084-8106, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32388501

RESUMO

Glioblastoma multiforme (GBM) is the most malignant neuroepithelial primary brain tumor and its mean survival time is 15 months after diagnosis. This study undertook to investigate the genome-wide and transcriptome-wide analyses of human high mobility group box (HMG-box) TF (transcript factor) families / HOX, TOX, FOX, HMG and SOX gene families, and their relationships to GBM. According to the TCGA-GBM profile analysis, differentially expressed HOX, FOX, HMG and SOX gene families (62 DEmRNA) were found in this study. We also analyzed DEmRNA (HMG-box related genes) co-expressed eight DElncRNA in GBM, and constructed a ceRNA network analysis as well. We constructed 50 DElncRNA-DEmiRNA-DEmRNA (HMG-box related genes) pairs between GBM and normal tissues. Then, risk genes SOX6 and SOX21 expression were correlated with immune infiltration levels in GBM. SOX6 also had a strong association with MAPT, GSK3B, FYN and DPYSL4, suggesting that they might be functional members in GBM.

5.
Int J Syst Evol Microbiol ; 70(5): 3179-3185, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32302275

RESUMO

A Gram-stain-positive, aerobic, non-motile and non-spore-forming actinobacterium, designated as F435T, was isolated from soil sample collected from the Cholistan Desert, Pakistan. The taxonomic position of the strain was established by using a polyphasic taxonomic approach. The cells were coccoid-shaped and found in single or arrangement of pairs. The novel strain grew at 15‒37 °C (optimum, 25‒30 °C), pH 7‒11 (optimum, pH 7-8) and in the presence of 0‒8% (w/v) NaCl (optimum, 0 %). Results of blast analysis based on 16S rRNA gene sequences showed that Auraticoccus monumenti MON 2.2T was its closest relative with 97.4 % similarity followed by Desertihabitans aurantiacus CPCC 204711T (95.2 %). In phylogenetic trees, strain F435T formed a robust cluster with the only member of the genus Auraticoccus. The peptidoglycan isomer present in the cell wall was ll-diaminopimelic acid. The major fatty acid was determined to be anteiso-C15 : 0. Characteristic polar lipids of the strain were diphosphatidylglycerol, phosphatidylglycerol, phosphoglycolipids and glycolipids. The predominant menaquinone was MK-9(H4). The genomic G+C content was calculated as 73.5 mol%. The digital DNA-DNA hybridization (GGDC) and average nucleotide identity (ANI) values between strain F435T and A. monumenti MON 2.2T were 24.6 and 81.8 %, respectively. Based on the results of phenotypic, chemotaxonomic, phylogenetic and phylogenomic analyses, strain F435T represents a novel specie of the genus Auraticoccus, for which the name Auraticoccus cholistanensis sp. nov. is proposed. The type strain is F435T (=JCM 33648T=CGMCC 1.17443T). The description of the genus Auraticoccus has also been emended.


Assuntos
Clima Desértico , Filogenia , Propionibacteriaceae/classificação , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Hibridização de Ácido Nucleico , Paquistão , Peptidoglicano/química , Fosfolipídeos/química , Propionibacteriaceae/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
6.
Org Biomol Chem ; 18(16): 3017-3021, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32236276

RESUMO

P,C-Stereogenic propargyl alcohols RC-3/SC-3' were prepared by the addition of (L)-menthyl-derived SPOs to propynals, which were converted to P,axial-stereogenic allenyl bisphosphine oxides. The chirality transfer was controlled by α-carbon via syn [2,3]-sigmatropic rearrangement. For SC-3' linking weak WDG on the alkynyl moiety, the chirality on the axis depended on stereogenic phosphorus.

7.
J Clin Ultrasound ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32266717

RESUMO

Foreign body ingestion is common in the pediatric population. We report a case of ingestion of sunflower seeds that migrated in the left neck through a pyriform sinus fistula, ultrasound plays an important role in preoperative diagnosis and is a useful tool for diagnosing both pyriform sinus fistulas and radiolucent foreign bodies.

9.
J Mol Recognit ; 33(7): e2837, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32017295

RESUMO

In mitosis, the accurate segregation of sister chromosomes relies on kinetochore, a multiple subunits complex assembled on centromere of each sister chromosome. As a core component of inner kinetochore, CENP-I plays important functions to mediate kinetochore assembly and supports the faithful chromosome segregation. The structures of the N-terminus and C-terminus of CENP-I homologs in complex with CENP-H/K have been reported, respectively. Unfortunately, the intramolecular interactions of CENP-I are poorly understood, and how CENP-I interacts with CENP-M remains unknown. Here, we verified a unique helix α11, which forms the intramolecular interactions with N-terminal HEAT repeats in fungal CENP-I. Deletion of the helix α11 exposed the hydrophobic surface and resulted in the in vitro protein aggregation of N-terminal HEAT repeats of fungal CENP-I. The corresponding helix and its intramolecular interaction are highly conserved in human CENP-I. Deletion of the corresponding helix in human CENP-I dramatically reduced the functional activity to interact with CENP-H and CENP-M. Mutations of the conserved residues on the helix in human CENP-I significantly weakened the binding to CENP-M, but not CENP-H, in HeLa cells. Therefore, our findings for the first time unveiled a conserved helix of CENP-I, which is important for the intramolecular interaction and function, and would be helpful for understanding the structure basis of how CENP-I mediates the kinetochore assembly during cell cycle and mitosis.

10.
Medicine (Baltimore) ; 99(6): e19004, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028411

RESUMO

BACKGROUND: Endoscopic tonsillectomy is associated with postoperative pain. Postoperative pain management remains to be improved in children. We aimed to investigate oxycodone preemptive analgesia in children undergoing endoscopic plasma total adenotonsillectomy. METHODS: 166 children with adenotonsillar hypertrophy were recruited at Wuhan Children's Hospital between 08/2016 and 03/2017. They were randomly assigned to receive SPOA (postoperative sufentanil), SPEA+SPOA (preemptive sufentanil and postoperative sufentanil), and OPEA+SPOA (preemptive oxycodone and postoperative sufentanil). The primary endpoint was serum c-fos levels. The secondary endpoints were the response entropy (RE) value, Pediatric Anesthesia Emergence Delirium (PAED) score, FLACC score, and adverse events. RESULTS: c-fos mRNA levels were increased significantly after surgery in the SPOA and SPEA+SPOA groups (P < .05). Postoperatively, c-fos mRNA levels were higher in the SPOA group compared with the OPEA+SPOA group (P = .044). The RE values increased in all groups after surgery (P < .05). At extubation, RE values were higher in the SPOA group compared with the SPEA+SPOA and OPEA+SPOA groups (P < .05). The PAED scores were higher in the SPOA group compared with the OPEA+SPOA group (P = .045). In the SPOA group, the FLACC scores were decreased at 24 h after surgery vs 4 hours (P = .044). Prediction probability (Pk) values indicated that RE and c-fos mRNA levels were quantitative predictors for early postoperative stress reaction after surgery. CONCLUSIONS: The subanalgesic dose of oxycodone (0.1 mg/kg) as preemptive analgesia could improve pain after endoscopic plasma total adenotonsillectomy in children.


Assuntos
Adenoidectomia , Analgésicos Opioides/uso terapêutico , Oxicodona/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Tonsilectomia , Actinas/sangue , Adenoidectomia/efeitos adversos , Adenoidectomia/métodos , Criança , Endoscopia/efeitos adversos , Endoscopia/métodos , Feminino , Humanos , Masculino , Proteínas Proto-Oncogênicas c-fos/sangue , Reação em Cadeia da Polimerase em Tempo Real , Sufentanil/uso terapêutico , Tonsilectomia/efeitos adversos , Tonsilectomia/métodos
11.
FASEB J ; 34(4): 5077-5091, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32052888

RESUMO

Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages. Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization- related gene IFN-γ was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization.

12.
Antibiotics (Basel) ; 8(4)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31783564

RESUMO

Rediscovery of known antibiotics from actinobacteria, especially Streptomyces, has become a bottleneck issue. Nowadays, more specific identification and dereplication could be acquired by a combination of modern analytic techniques with various databases. In this study, 261 actinobacterial strains were isolated from 8 mangrove soil samples by culture-dependent method. A total of 83 strains were selected to evaluate antibacterial activities and mechanisms by disc diffusion method and a unique double fluorescent protein reporter system (pDualrep2), respectively. Thirty-two strains exhibited antagonistic activity against at least one of the "ESKAPE" pathogens. Four Streptomyces strains (B475, B486, B353, and B98) showed strong inhibitory activity against Gram-positive bacteria and induced DNA damage SOS response. One Micromonospora strain (B704) exhibited inhibitory activity against several pathogens and induced attenuation-based translational inhibitors reporter. Seven members of quinoxaline-type antibiotics including quinomycin A, quinomycin monosulfoxide, and other five putative new analogues were found from the culture broth of strain B475 by a combination of anti-MRSA guide, HPTLC, HPLC-UV, and UPLC-UV-HRESIMS/MS analysis, Chemspider searching, and MS/MS-based molecular networking analysis. In conclusion, this study not only demonstrated that mangrove is a rich source of actinobacteria with the potentially new antibiotics but showed rapid dereplication of known antibiotics in the early stage can improve efficiency for the discovery of new antibiotics.

13.
Dis Markers ; 2019: 5096860, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772689

RESUMO

In this study, we evaluated the relationship between circulating betatrophin levels and obesity. Obesity is a common public health problem that is increasing globally. Betatrophin, a newly identified protein, is predominantly expressed in white and brown fat tissues and in the liver. Growing evidence suggests that betatrophin plays a pivotal role in metabolism, including the synthesis and degradation of lipids in cells, and adipocyte differentiation. Previous studies have assessed the association between circulating betatrophin levels and obesity; however, this relationship remains unclear. Therefore, our study is aimed at examining the impact of betatrophin on obesity using a meta-analysis of the current evidence. We performed a meta-analysis to quantify the relationship between betatrophin levels and obesity. A literature search was conducted through the EMBASE, Web of Science, and MEDLINE databases. Retrieved studies were screened, without any language restrictions to identify relevant literature published up to December 2018. Observational studies, in which the association between circulating concentrations of betatrophin and obesity was evaluated, were considered suitable for the systematic review. Of the 65 manuscripts retrieved, 9 datasets from 6 studies, involving 681 participants, detected an association between circulating betatrophin and obesity. Circulating betatrophin levels of obese subjects were higher than those of nonobese subjects (random - effects weighted mean difference (WMD) = 0.250 µg/mL, 95% CI: 0.048-0.451, I 2 = 94.8%, p = 0.015), yet with significant between-study heterogeneity. This heterogeneity appeared to be modified by glycemic status but not by age, the ELISA kits used, sample source, or body mass index. The high circulating betatrophin concentration may directly increase the risk of obesity in adults. Betatrophin may serve as a therapeutic target for obesity in adults.


Assuntos
Proteínas Semelhantes a Angiopoietina/sangue , Obesidade/sangue , Hormônios Peptídicos/sangue , Humanos
14.
ACS Appl Mater Interfaces ; 11(50): 47358-47364, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31755694

RESUMO

Wearable epidermal sensors are attracting growing interests in human activity monitoring and flexible touch display, but they are still limited by the poor self-healing property and the difficult dissolvable feature. Herein, we report polyvinyl alcohol (PVA)-stabilized liquid metal particles (LMPs) (PVA-LMPs) hydrogels with excellent self-healing performance and the dissolvable feature for wearable epidermal sensors, constructed by dispersing LMPs of eutectic gallium and indium into the borate-modified PVA polymer networks. Interestingly, the PVA-LMPs hydrogels exhibited excellent electrically and mechanically self-healing ability. Moreover, the PVA-LMPs hydrogel can be fabricated as epidermal sensors, which can accurately monitor the human activities. Additionally, the epidermal sensors are dissolvable, showing an attractive feature for on demand transient electronics. It is demonstrated that the hydroxyl groups of PVA can stabilize LMPs via hydrogen-bonding interactions. Furthermore, the dynamic cross-linking bonds between hydrogels and LMPs can rupture and coalesce reversibly in the hydrogel network, which endow the hydrogels with both electrically and mechanically self-healing ability. This work shows the potential of constructing next-generation multifunctional hydrogel-based epidermal sensors for human activity monitoring, wearable healthcare diagnosis, portable electronics, and robot tactile systems.

15.
Int J Mol Med ; 44(3): 982-994, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31524235

RESUMO

Therapeutic agents used to treat sepsis­induced cardiac dysfunction are designed to suppress tumor necrosis factor (TNF)­α release and inhibit cell apoptosis. Exogenous administration of growth arrest­specific 6 (Gas6) exerts several biological and pharmacological effects; however, the role of Gas6 in sepsis­induced myocardial dysfunction remains unclear. In this study, H9C2 cardiomyocytes were stimulated with LPS (10 µg/ml) to mimic septic cardiac dysfunction and Gas6 (100 ng/ml) was applied exogenously. Subsequently, mitogen­activated protein kinase (MAPK) and nuclear factor (NF)­κB activation, TNF­α expression, and apoptosis in the presence or absence of TP­0903 (15 nM) and Wortmannin (3 nM) were evaluated. The morphological alterations of H9C2 cells were visualized by phase­contrast microscopy. Cell viability was determined using the Cell Counting kit 8 assay and lactate dehydrogenase release, and TNF­α release was analyzed by ELISA analysis. Cell apoptosis was analyzed by flow cytometry and TUNEL assay. Nuclear morphological alterations were detected by Hoechst staining and caspase­3 activity was measured using biochemical methods. The expression levels of Bax and Bcl­2, and the phosphorylation and expression levels of Axl, Akt, IκB­α, p65, c­Jun N­terminal protein kinase (JNK), extracellular signal­regulated kinase (ERK) and p38 were determined by western blotting. Furthermore, immunofluorescence analysis was performed to visualize translocation of NF­κB p65. The results demonstrated that Gas6 suppressed TNF­α release and inhibited cell apoptosis, and attenuated nuclear factor (NF)­κB and mitogen­activated protein kinase (MAPK) activation via the Axl/PI3K/Akt pathway. Furthermore, the cardioprotective properties of Gas6 on the suppression of LPS­induced TNF­α release and apoptosis were abolished by treatment with TP­0903 (an Axl inhibitor) and Wortmannin (a PI3K inhibitor). Pretreatment with TP­0903 and Wortmannin abrogated the effects of Gas6 on phosphorylated­IκB­α, IκB­α, NF­κB, ERK1/2, JNK and p38 MAPK. These findings suggested that activation of Axl/PI3K/Akt signaling by Gas6 may inhibit LPS­induced TNF­α expression and apoptosis, as well as MAPK and NF­κB activation.


Assuntos
Apoptose/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Lipopolissacarídeos/farmacologia , Modelos Biológicos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
16.
Clin Cancer Res ; 25(24): 7275-7280, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31366601

RESUMO

The FDA-approved mogamulizumab-kpkc, a CC chemokine receptor type 4 (CCR4)-directed mAb, in August 2018 for treatment of adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy. Regular approval was based on a randomized, open-label trial that randomized 372 such patients, with a median of 3 prior systemic therapies, to either mogamulizumab-kpkc or vorinostat. Investigator-assessed progression-free survival (PFS) was statistically significantly longer in the mogamulizumab-kpkc arm, which had an estimated median PFS of 7.6 months [95% confidence interval (CI), 5.6-10.2] compared with 3.1 months (95% CI, 2.8-4.0) in the vorinostat arm (HR = 0.53; 95% CI, 0.41-0.69). The confirmed overall response rate was 28% and 5%, respectively (P < 0.001), based on global composite response criteria. Adverse reactions occurring in at least 20% of mogamulizumab-kpkc recipients included rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection. Serious adverse reactions occurred in 36% of patients, most often from infection. The prescribing information includes warnings for dermatologic toxicity, infusion reactions, infections, autoimmune complications, and complications of allogeneic hematopoietic stem cell transplantation, including severe and steroid-refractory graft-versus-host disease.See related commentary by Larocca et al., p. 7272.

17.
Circ Res ; 125(8): 728-743, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455181

RESUMO

Rationale: The constrained mitochondria in cardiomyocytes communicate with each other, through mitochondrial kissing or nanotunneling, forming a dynamically continuous network to share content and transfer signals. However, the molecular mechanism of cardiac inter-mitochondrial communication is unclear. Objective: To determine the molecular mechanism underlying the robust inter-mitochondrial communication and its pathophysiological relevance in the heart. Methods and Results: By mitochondria-targeted expressing the photoactivatable green fluorescent protein, we revealed that most mitochondrial nanotubes bridge communicating mitochondrial pairs were associated with microtubules. Miro2 (mitochondrial Rho GTPase), the outer mitochondrial membrane protein which usually mediates mitochondrial transport within cells, accompanied with mitochondrial nanotubes along microtubules in adult cardiomyocytes. Adenovirus mediated expression of Miro2 in cardiomyocytes accelerated inter-mitochondrial communication through increasing mitochondrial nanotunneling and mitochondrial kissing between adjacent mitochondrial pairs. In transverse aortic constriction-induced hypertrophic mouse hearts Miro2 protein was declined, accompanied with decreased inter-mitochondrial communication. Miro2 transgenic mice showed ameliorated cardiac function, increased mitochondrial nanotube formation and inter-mitochondrial communication, and improved mitochondrial function after transverse aortic constriction. E3 ubiquitin ligase Parkin was increased in transverse aortic constriction mouse hearts and phenylephrine stimulation-induced hypertrophic cardiomyocytes. Inhibition of proteasome blocked phenylephrine-induced decrease of Miro2, and Parkin overexpression led to the decrease of Miro2. Conclusions: Mitochondrial Miro2 expression levels regulate inter-mitochondrial communication along microtubules in adult cardiomyocytes, and degradation of Miro2 through Parkin-mediated ubiquitination contributes to impaired inter-mitochondrial communication and cardiac dysfunction during hypertrophic heart diseases.Visual Overview: An online visual overview is available for this article.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31281398

RESUMO

Mangrove is a rich and underexploited ecosystem with great microbial diversity for discovery of novel and chemically diverse antimicrobial compounds. The goal of the study was to explore the pharmaceutical actinobacterial resources from mangrove soil and gain insight into the diversity and novelty of cultivable actinobacteria. Consequently, 10 mangrove soil samples were collected from Futian and Maoweihai of China, and the culture-dependent method was employed to obtain actinobacteria. A total of 539 cultivable actinobacteria were isolated and distributed in 39 genera affiliated to 18 families of 8 orders by comparison analysis of partial 16S rRNA gene sequences. The dominant genus was Streptomyces (16.0 %), followed by Microbacterium (14.5 %), Agromyces (14.3 %), and Rhodococcus (11.9 %). Other 35 rare actinobacterial genera accounted for minor proportions. Notably, 11 strains showed relatively low 16S rRNA gene sequence similarities (< 98.65 %) with validly described species. Based on genotypic analyses and phenotypic characteristics, 115 out of the 539 actinobacterial strains were chosen as representative strains to test their antibacterial activities against "ESKAPE" bacteria by agar well diffusion method and antibacterial mechanism by the double fluorescent protein reporter system. Fifty-four strains in 23 genera, including 2 potential new species, displayed antagonistic activity in antibacterial assay. Meanwhile, 5 strains in 3 genera exhibited inhibitory activity on protein biosynthesis due to ribosome stalling. These results demonstrate that cultivable actinobacteria from mangrove soil are potentially rich sources for discovery of new antibacterial metabolites and new actinobacterial taxa.

19.
Int J Mol Sci ; 20(12)2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31234600

RESUMO

Obesity is a serious health challenge worldwide and is associated with various comorbidities, including dyslipidemia, type 2 diabetes, and cardiovascular disease. Developing effective strategies to prevent obesity is therefore of paramount importance. One potential strategy to reduce obesity is to consume calcium, which has been implicated to be involved in reducing body weight/fat. In this review, we compile the evidence for the anti-obesity roles of calcium in cells, animals, and humans. In addition, we summarize the possible anti-obesity mechanisms of calcium, including regulation of (a) adipogenesis, (b) fat metabolism, (c) adipocyte (precursor) proliferation and apoptosis, (d) thermogenesis, (e) fat absorption and excretion, and (f) gut microbiota. Although the exact anti-obesity roles of calcium in different subjects and how calcium induces the proposed anti-obesity mechanisms need to be further investigated, the current evidence demonstrates the anti-obesity effects of calcium and suggests the potential application of dietary calcium for prevention of obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Cálcio na Dieta/farmacologia , Suplementos Nutricionais , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Termogênese/efeitos dos fármacos
20.
J Org Chem ; 84(13): 8423-8439, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31136177

RESUMO

Various functional secondary and tertiary phosphines, or their derivatives, containing stationary chiral phosphorus and flexible chiral axis were prepared, which could be further modified to afford diversely chelating ligands. The flexible axial chirality was fixed by stereogenic phosphorus via a cyclic linkage of chemical bonds or coordination with a metallic ion.

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