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1.
Front Pharmacol ; 11: 248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218733

RESUMO

With the escalating costs in drug development, discovering new uses of approved drugs, i.e., drug repurposing, has attracted increasing interest. Spermidine and spermine are important polyamines for most cells and their biosynthesis are strictly regulated by the polyamine metabolic network. In cancerous cells and tumor environments, the concentrations of polyamines are much higher than in normal cells. During the synthesis of spermidine and spermine, an amino-propyl group is provided by decarboxylated S-adenosylmethionine, and the latter is generated from S-adenosylmethionine by AdoMetDC (AdoMet decarboxylase). Therefore, as a rate-limiting enzyme in the biosynthesis of spermidine and spermine, AdoMetDC has been an attractive drug target in cancer studies. In the last decades, many AdoMetDC inhibitors have been discovered, and several AdoMetDC inhibitors are under clinical trials, but unfortunately, none of them have been approved yet. To overcome the high costs in time and money for discovering de novo inhibitors, we set out to repurpose clinic drugs as AdoMetDC inhibitors. We used steric-clashes alleviating receptors (SCAR), a computer-aided drug discovery strategy developed by us recently for in silico screening. By combining computational screening and experimental validation, we successfully identified two approved drugs that have inhibitory potency on AdoMetDC's enzymatic activity. SCAR was previously shown to be suitable for the discovery of both covalent and non-covalent inhibitors, and this work further demonstrated the value of the SCAR strategy in drug repurposing.

2.
Life Sci ; 250: 117551, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32179075

RESUMO

AIMS: Increasing evidence indicates that FK866, a specific noncompetitive nicotinamide phosphoribosyl transferase inhibitor, exhibits a protective effect on acute lung injury (ALI). Autophagy plays a pivotal role in sepsis-induced ALI. However, the contribution of autophagy and the underlying mechanism by which FK866-confered lung protection remains elusive. Herein, we aimed to study whether FK866 could alleviate sepsis-induced ALI via the JNK-dependent autophagy. MAIN METHODS: Male C57BL/6 mice were subjected to cecal ligation and puncture (CLP) to establish the polymicrobial sepsis mice model, and treated with FK866 (10 mg/kg) at 24, 12 and 0.5 h before the CLP procedure. The lung protective effects were measured by lung histopathology, tissue edema, vascular leakage, inflammation infiltration, autophagy-related protein expression and JNK activity. A549 cells were stimulated with LPS (1000 ng/ml) to generate the ALI cell model, and pretreated with FK866 or SP600125 for 30 min to measure the autophagy-related protein expression and JNK activity. KEY FINDINGS: Our results demonstrated that FK866 reduced lung injury score, tissue edema, vascular leakage, and inflammatory infiltration, and upregulated autophagy. The protective effect of autophagy conferred by FK866 on ALI was further clarified by using 3-methyladenine (3MA) and rapamycin. Additionally, the activity of JNK was suppressed by FK866, and inhibition of JNK promoted autophagy and showed a benefit effect. SIGNIFICANCE: Our study indicates that FK866 protects against sepsis-induced ALI by induction of JNK-dependent autophagy. This may provide new insights into the functional mechanism of NAMPT inhibition in sepsis-induced ALI.

3.
Sci Rep ; 10(1): 4434, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157110

RESUMO

The study aimed to compare the tumor response to and complications of doxorubicin-eluting CalliSphere bead-transarterial chemoembolization (DEB-TACE) using small- and medium-sized beads in patients with hepatocellular carcinoma (HCC) who underwent multiple rounds of oncology therapies. Sixty patients with intermediate stage HCC who had previously received multiple oncology therapies underwent DEB-TACE with CalliSpheres of 100-300 µm (small bead group, n = 34) or 300-500 µm (medium bead group, n = 26) in diameter between October 2016 and December 2018. Adverse events and the response rate of the index tumor based on the modified Response Evaluation Criteria in Solid Tumors at 3 months post-TACE were compared between the groups. The rates of complete response, partial response, stable disease, and progressive disease were 35.4%, 29.4%, 17.6%, and 17.6%, respectively, for the small bead group and 33.1%, 23.1%, 20.8%, and 23.0%, respectively, for the medium bead group, showing no significant between-group differences (P > 0.05). Common Terminology Criteria for Adverse Events version 4.0 grade 3/4 adverse events were reported in 8 patients in the small bead group and in no patients in the medium bead group, showing a significant group difference (P < 0.01). Major complications included 8 events of ischemic hepatitis, 2 of biloma, and 2 of severe liver abscess. DEB-TACE using CalliSpheres of 300-500 µm was associated with a comparable rate of tumor response but lower rate of complications compared with that using CalliSpheres of 100-300 µm for HCC treatment in patients who had already undergone multiple rounds of oncology therapies.

4.
Int J Nanomedicine ; 15: 137-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021170

RESUMO

Purpose: Traditional chemotherapy is accompanied by significant side effects, which, in many aspects, limits its treatment efficacy and clinical applications. Herein, we report an oxidative responsive polymersome nanosystem mediated by near infrared (NIR) light which exhibited the combination effect of photodynamic therapy (PDT) and chemotherapy. Methods: In our study, poly (propylene sulfide)20-bl-poly (ethylene glycol)12 (PPS20-b-PEG12) block copolymer was synthesized and employed to prepare the polymersome. The hydrophobic photosensitizer zinc phthalocyanine (ZnPc) was loaded in the shell and the hydrophilic doxorubicin hydrochloride (DOX·HCl) in the inner aqueous space of the polymersome. Results: Under the irradiation of 660 nm NIR light, singlet oxygen 1O2 molecules were generated from ZnPc to oxidize the neighbouring sulfur atoms on the PPS block which eventually ruptured the intact structure of polymersomes, leading to the release of encapsulated DOX·HCl. The released DOX and the 1O2 could achieve a combination effect for cancer therapy if the laser activation and drug release occur at the tumoral sites. In vitro studies confirmed the generation of singlet oxygen and DOX release by NIR irradiation. In vivo studies showed that such a combined PDT-chemotherapy nanosystem could accumulate in A375 tumors efficiently, thus leading to significant inhibition on tumor growth as compared to PDT (PZ group) or chemotherapy alone (DOX group). Conclusion: In summary, this oxidation-sensitive nanosystem showed excellent anti-tumor effects by synergistic chemophotodynamic therapy, indicating that this novel drug delivery strategy could potentially provide a new means for cancer treatments in clinic.

5.
mBio ; 11(1)2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071270

RESUMO

Microbial photoautotroph-heterotroph interactions underlie marine food webs and shape ecosystem diversity and structure in upper ocean environments. Here, bacterial community composition, lifestyle preference, and genomic- and proteomic-level metabolic characteristics were investigated for an open ocean Synechococcus ecotype and its associated heterotrophs over 91 days of cocultivation. The associated heterotrophic bacterial assembly mostly constituted five classes, including Flavobacteria, Bacteroidetes, Phycisphaerae, Gammaproteobacteria, and Alphaproteobacteria The seven most abundant taxa/genera comprised >90% of the total heterotrophic bacterial community, and five of these displayed distinct lifestyle preferences (free-living or attached) and responses to Synechococcus growth phases. Six high-quality genomes, including Synechococcus and the five dominant heterotrophic bacteria, were reconstructed. The only primary producer of the coculture system, Synechococcus, displayed metabolic processes primarily involved in inorganic nutrient uptake, photosynthesis, and organic matter biosynthesis and release. Two of the flavobacterial populations, Muricauda and Winogradskyella, and an SM1A02 population, displayed preferences for initial degradation of complex compounds and biopolymers, as evinced by high abundances of TonB-dependent transporters (TBDTs), glycoside hydrolase, and peptidase proteins. Polysaccharide utilization loci present in the flavobacterial genomes influence their lifestyle preferences and close associations with phytoplankton. In contrast, the alphaproteobacterium Oricola sp. population mainly utilized low-molecular-weight dissolved organic carbon (DOC) through ATP-binding cassette (ABC), tripartite ATP-independent periplasmic (TRAP), and tripartite tricarboxylate transporter (TTT) transport systems. The heterotrophic bacterial populations exhibited complementary mechanisms for degrading Synechococcus-derived organic matter and driving nutrient cycling. In addition to nutrient exchange, removal of reactive oxygen species and vitamin trafficking might also contribute to the maintenance of the Synechococcus-heterotroph coculture system and the interactions shaping the system.IMPORTANCE The high complexity of in situ ecosystems renders it difficult to study marine microbial photoautotroph-heterotroph interactions. Two-member coculture systems of picocyanobacteria and single heterotrophic bacterial strains have been thoroughly investigated. However, in situ interactions comprise far more diverse heterotrophic bacterial associations with single photoautotrophic organisms. In the present study, combined metagenomic and metaproteomic data supplied the metabolic potentials and activities of uncultured dominant bacterial populations in the coculture system. The results of this study shed light on the nature of interactions between photoautotrophs and heterotrophs, improving our understanding of the complexity of in situ environments.

6.
J Craniofac Surg ; 31(2): 534-537, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31977714

RESUMO

BACKGROUND AND OBJECTIVE: Craniofacial malignant tumors require not only extended resection but also appropriate reconstruction to restore appearance, which remains a major challenge. Here the authors introduced the application of superficial temporal artery (STA) flap in wound repairing after the resection of craniofacial malignant tumors. METHODS: From January 2015 to December 2018, 16 patients with craniofacial malignant tumors were enrolled into the study, including squamous cell carcinoma (n = 6), basal cell carcinoma (n = 3), melanoma (n = 4), neuroendocrine carcinoma (n = 2), and dermatofibrosarcoma protuberance (n = 1). All of the tumors underwent extended resection. The defects formed were repaired by flaps pedicled with superior or frontal branch of STA. Donor sites were repaired with skin grafts. Patients were followed up for 6 months to 3 years to monitor the recurrence of tumor. RESULTS: All the flaps survived well. Venous congestion occurred in two cases but resolved after blood-letting and application of drugs promoting venous draining. During the follow-up, no recurrence of tumors was observed and the appearance of flaps was satisfying. But flap donor sites suffered from relatively poor appearance or alopecia deformity. CONCLUSIONS: The STA flap is reliable for wound repairing after resection of craniofacial malignant tumors. The STA parietal branch flap is preferred for repairing scalp defects, while the STA frontal branch flap is preferred for repairing facial defects. However, the STA flap should be used prudently due to its disadvantage of the deformity in scalp donor sites.

7.
Inflammation ; 43(1): 32-43, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894450

RESUMO

Air pollution events frequently occur in China during the winter. Most investigations of pollution studies have focused on the physical and chemical properties of PM2.5. Many of these studies have indicated that PM2.5 exacerbates asthma or eosinophil inflammation. However, few studies have evaluated the relationship between bacterial loads in PM2.5, and especially pathogenic bacteria and childhood asthma. Airborne PM2.5 samples from heavily polluted air were collected in Hangzhou, China between December 2014 and January 2015. PM2.5 and ovalbumin (OVA) were intratracheally administered twice in 4-week intervals to induce the allergic pulmonary inflammation in adolescent C57/BL6 mice. PM2.5 exposure caused neutrophilic alveolitis and bronchitis. In the presence of OVA, the levels of the Th2 cytokines IL-4, IL-12, and IL-17 were significantly increased in bronchoalveolar lavage fluids (BALF) after PM2.5 exposure, while eosinophil infiltration and mucin secretion were also induced. In addition to adjuvant effects on OVA-induced allergic inflammation, PM2.5 exposure also led to the maturation of dendritic cells. These results suggest that PM2.5 exposure may aggravate lung eosinophilia and that PM2.5-bound microbial can exacerbate allergic and inflammatory lung diseases.

8.
J Mater Chem B ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31984984

RESUMO

Motion recognition and information interaction sensors with flexibility and stretchability are key functional modules as interactive media between the mechanical motions and electric signals in an intelligent robotic and rehabilitation training system. Nanogenerators have many useful applications in the field of intelligent interaction, with the advantages of a self-powered sensing ability, easy fabrication, considerable sensitivity and reliability. However, the singularity of the sensing mode limits its applications. Hence, in this research, a flexible and stretchable dual mode nanogenerator (FSDM-NG) for human motion sensing and information interaction, based on the integration of piezoelectric and triboelectric principles was developed. In piezoelectric mode, the FSDM-NG can effectively monitor the bending angle of joints (finger, wrist and elbow) from 30° to 90°. In triboelectric mode, text and logic information transfer are encoded using Morse code and logic gates, respectively. In addition, the device has good adhesion and biosafety, and is robust which makes it work normally even in under water environments. Combining these two sensing mechanisms, multiple modes of sensing from touch and stretch based on the FSDM-NG can be achieved for information interaction in real time. The proposed sensor has the potential to be adapted for more complex sensing, which may provide new applications for intelligent interaction of robots and in the rehabilitation training field.

9.
ACS Sens ; 5(2): 319-326, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31913018

RESUMO

Hydrogen sulfide (H2S) is an important cellular signaling molecule, and its physiological and pathophysiological properties have been under intensive investigation. In this study, a novel ratiometric fluorescent H2S donor (HSD-B) has been developed, which exhibited the following advantages: (i) scavenging ROS and producing H2S simultaneously; (ii) providing ratiometric fluorescence for visualization and quantification of H2S releasing; and (iii) targeting mitochondrion specifically. Moreover, it demonstrated protective effects on myocardial ischemia reperfusion injury in a cellular model. These attractive features promise this HSD-B as a fluorescent H2S donor for future research studies.

10.
Eur J Cancer Prev ; 29(2): 165-173, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31609809

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are recently identified as gene regulators in mammals and play important roles in carcinogenesis of cancer. For example, circRNA_PTN has been recognized as a biomarker of human cancer and is overexpressed in glioma. The molecular function of circRNA_PTN and its downstream targets in glioma, however, remains elusive. METHODS: Quantitative polymerase chain reaction analysis was used to measure the expression of circular RNA pleiotrophin (circ_PTN) and miR-122. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, propidium iodide and Annexin-V/propidium iodide assay were performed to determine cell proliferation and apoptosis of glioma cells. Circular RNA Interactome and TargetScan were used to predict the potential microRNA targeting of circ_PTN and the potential targets of miR-122, respectively. Luciferase activity assay was used to validate these interactions. Downstream molecular mechanisms, including SRY-box transcription factor 6 (SOX6), extracellular regulated protein kinases (ERK), Cyclin D1, B-cell lymphoma-2 (BCL-2) and BCL2 associated X, apoptosis regulator (BAX), were determined by western blot. RESULTS: Circ_PTN was overexpressed in glioma cells, and its knockdown induced cell proliferation inhibition, cell cycle arrest and apoptosis in glioma cells. The target microRNA of circ_PTN was predicted to be miR-122, the expression of which was negatively correlated with circ_PTN in glioma cells. Moreover, SOX6 was predicted as a potential target of miR-122, and miR-122 overexpression decreased SOX6 expression. MiR-122 inhibitor reversed the tumor-suppressing effects of circ_PTN knockdown, while overexpression of SOX6 impaired the miR-122 overexpression-induced cell growth inhibition and apoptosis. In addition, mitogen activated kinase-like protein (MAPK)/ERK pathway was involved in circ_PTN/miR-122/SOX6 axis. CONCLUSIONS: Circ_PTN acted as a sponge of miR-122 and upregulated miR-122 target SOX6, thus promoting carcinogenesis of glioma cells.

11.
J Plast Surg Hand Surg ; 54(1): 40-46, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31581878

RESUMO

Soft tissue reconstruction of the distal lower leg and foot sole is a challenge for surgeons. In this article, we describe our experience and outcomes with distal lower leg and foot sole reconstruction using the medial plantar flap. From January 2007 to December 2017, 29 consecutive patients from our department underwent reconstruction of soft tissue defects over the distal lower leg, heel and plantar forefoot using medial plantar flaps. Of the 29 patients, the defects were located in the distal lower leg (n = 8 [27.6%]), heel (n = 14 [48.3%]) and plantar forefoot (n = 7 [24.1%]). The mean follow-up period was 18.6 months, 28 (96.6%) survived completely. Lateral partial necrosis occurred in one flap. No patient had recurrence of ulcer and two (6.9%) patients died within 1 year post-reconstruction owing to metastatic malignant melanoma. At last follow-up, all survived patients could walk for more than 1 h in normal shoes. All donor sites were covered with a split-thickness skin graft, no early nor late complications were encountered, and no patients complained about the donor site scar. The medial plantar flap may be considered as an effective method for the repair of small to medium soft tissue defects in the distal lower leg, heel and plantar forefoot.

12.
Food Chem ; 305: 125447, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499289

RESUMO

A novel α-amylase gene (RmAmyA) from Rhizomucor miehei was cloned and expressed in Pichia pastoris. RmAmyA showed 70% amino acid identity with the α-amylase from Rhizomucor pusillus. A high α-amylase activity of 29,794.2 U/mL was found through high cell density fermentation. The molecular mass of RmAmyA was determined to be 49.9 kDa via SDS-PAGE. RmAmyA was optimally active at 75 °C and pH 6.0, and it did not require Ca2+ to improve its activity. It exhibited broad substrate specificity towards amylose, amylopectin, soluble starch, pullulan, and cyclodextrins. High level of maltose (54%, w/w) was produced after liquefied starch was hydrolysed with RmAmyA for 16 h. Moreover, the addition of RmAmyA into Chinese steamed bread resulted in 7.7% increment in the specific volume, and 17.2% and 11.5% reduction in the chewiness and hardness, respectively. These results indicate that RmAmyA might be a potential candidate for applications in the food industry.


Assuntos
Maltose/metabolismo , Rhizomucor/enzimologia , alfa-Amilases/metabolismo , Pão/análise , Indústria Alimentícia , Concentração de Íons de Hidrogênio , Hidrólise , Pichia/metabolismo , Amido/metabolismo , Especificidade por Substrato , Temperatura Ambiente , alfa-Amilases/química , alfa-Amilases/genética
13.
Food Chem ; 309: 125709, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31708343

RESUMO

To produce manno-oligosaccharides from cassia gum, a mutated glycoside hydrolase family 134 ß-mannanase gene (mRmMan134A) from Rhizopus microsporus var. rhizopodiformis F518 was expressed in Pichia pastoris and a high expression level (3680 U mL-1) was obtained through high cell density fermentation. mRmMan134A exhibited maximum activity at pH 5.5 and 50 °C. It was then subjected to hydrolyze cassia gum with 70.6% of overall yield of manno-oligosaccharides. From the hydrolysate, seven components (F1-F7) were separated and identified as mannose, mannobiose, galactose, mannotriose, mannotetraose, 61-α-d-galactosyl-ß-d-mannobiose, and mannopentaose, respectively. According to in vitro fermentation, the manno-oligosaccharides were able to promote the growth of three Bifidobacterium strains and six Lactobaillus strains with 3.0-fold increment in culture absorbance, and these strains preferred manno-oligosaccharides with degree of polymerization (DP) 2-3 rather than those with DP 4-5. Novel manno-oligosaccharides from cassia gum with promising prebiotic activity were provided in the present study.


Assuntos
Cassia/metabolismo , Oligossacarídeos/metabolismo , Prebióticos , beta-Manosidase/metabolismo , Técnicas de Cultura Celular por Lotes , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Hidrólise , Manose/metabolismo , Oligossacarídeos/isolamento & purificação , Oligossacarídeos/farmacologia , Rhizopus/enzimologia , Temperatura Ambiente , beta-Manosidase/genética
14.
Nat Commun ; 10(1): 5472, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784532

RESUMO

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.

15.
ACS Appl Mater Interfaces ; 11(46): 43631-43640, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31664813

RESUMO

Shape memory hydrogels have drawn increasing attention in recent years. Practical applications require these hydrogels to have good mechanical properties as well as contactless stimulations to trigger the shape deformations. Here we report a stiff and tough shape memory hydrogel that can transform to various configurations sequentially by phototriggered site-specific deformations. Response of the shape memory hydrogel to near-infrared (NIR) light irradiation was achieved by incorporating gold nanorods (AuNRs) into the glassy gel matrix of poly(methacrylic acid-co-methacrylamide) without compromising the excellent mechanical properties. Owing to the photothermal effect of the AuNRs, the localized temperature rise led to a dramatic decrease in Young's modulus (from 200 to 2 MPa) of the prestretched hydrogel and bending deformation with a programmable direction and amplitude. More complex three-dimensional configurations can be obtained by multidirectional prestretching and shape memorizing the individual parts of the nanocomposite hydrogel. Furthermore, the AuNRs embedded in the gel were aligned along the prestretching direction, leading to anisotropic plasmon resonance. These photomediated programmable deformations of tough shape memory hydrogels should find applications in the biomedical and engineering fields.

16.
Nanomedicine (Lond) ; 14(18): 2423-2440, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31549585

RESUMO

Aim: We developed a polycaprolactone-based nanoparticle (NP) to encapsulate tryptanthrin derivative CY-1-4 and evaluated its antitumor efficacy. Materials & methods: CY-1-4 NPs were prepared and evaluated for their cytotoxicity and associated mechanisms, indoleamine 2,3-dioxygenase (IDO)-inhibitory ability, immunogenic cell death (ICD)-inducing ability and antitumor efficacy. Results: CY-1-4 NPs were 123 nm in size. In vitro experiments indicated that they could both induce ICD and inhibit IDO. In vivo studies indicated that a medium dose reduced 58% of the tumor burden in a B16-F10-bearing mouse model, decreased IDO expression in tumor tissues and regulated lymphocytes subsets in spleen and tumors. Conclusion: CY-1-4 is a potential antitumor candidate that could act as a single agent with combined functions of IDO inhibition and ICD induction.

17.
Appl Opt ; 58(19): 5159-5164, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503609

RESUMO

Catenary optics has attracted much interest due to its unique properties in wave-front manipulation, field enhancement, and dispersion engineering. In this paper, the applications of catenary optics in the near-field lithography are studied. The catenary shaped nanostructures and tip-insulator-metal (TIM) structures are simultaneously utilized to increase the contrast ratio of the focal plane and to give rise to a sharp focusing focal spot with high intensity. Moreover, the full width at half-maximum of the focal spot maintains well below the diffraction limit. The proposed catenary TIM structure may improve the quality of near-field lithography and find applications in super-resolution near-field direct writing nano-lithography.

18.
mSystems ; 4(5)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506262

RESUMO

Aerobic anoxygenic photoheterotrophic bacteria (AAPB) represent a bacteriochlorophyll a-containing functional group. Substantial evidence indicates that highly conserved photosynthetic gene clusters (PGCs) of AAPB can be transferred between species, genera, and even phyla. Furthermore, analysis of recently discovered PGCs carried by extrachromosomal replicons (exPGCs) suggests that extrachromosomal replicons (ECRs) play an important role in the transfer of PGCs. In this study, 13 Roseobacter clade genomes from seven genera that harbored exPGCs were used to analyze the characteristics and evolution of PGCs. The identification of plasmid-like and chromid-like ECRs among PGC-containing ECRs revealed two different functions: the spread of PGCs among strains and the maintenance of PGCs within genomes. Phylogenetic analyses indicated two independent origins of exPGCs, corresponding to PufC-containing and PufX-containing puf operons. Furthermore, the two different types of operons were observed within different strains of the same Tateyamaria and Jannaschia genera. The PufC-containing and PufX-containing operons were also differentially carried by chromosomes and ECRs in the strains, respectively, which provided clear evidence for ECR-mediated PGC transfer. Multiple recombination events of exPGCs were also observed, wherein the majority of exPGCs were inserted by replication modules at the same genomic positions. However, the exPGCs of the Jannaschia strains comprised superoperons without evidence of insertion and therefore likely represent an initial evolutionary stage where the PGC was translocated from chromosomes to ECRs without further combinations. Finally, a scenario of PGC gain and loss is proposed that specifically focuses on ECR-mediated exPGC transfer to explain the evolution and patchy distribution of AAPB within the Roseobacter clade.IMPORTANCE The evolution of photosynthesis was a significant event during the diversification of biological life. Aerobic anoxygenic photoheterotrophic bacteria (AAPB) share physiological characteristics with chemoheterotrophs and represent an important group associated with bacteriochlorophyll-dependent phototrophy in the environment. Here, characterization and evolutionary analyses were conducted for 13 bacterial strains that contained photosynthetic gene clusters (PGCs) carried by extrachromosomal replicons (ECRs) to shed light on the evolution of chlorophototrophy in bacteria. This report advances our understanding of the importance of ECRs in the transfer of PGCs within marine photoheterotrophic bacteria.

19.
Biomed Res Int ; 2019: 3456719, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534957

RESUMO

Dihydroartemisinin (DHA), which is considered to be one of the active compounds within Artemisia annua, has extensively been used in recent years as the most effective drug against malaria, having many biological functions including anticancer, antifungal, and immunomodulatory activities. However, DHA plays a role in the regulation of the proliferation and human mesenchymal stem cells (hMSCs) osteogenic differentiation that remains unknown. We explored DHA's effect on hMSCs' proliferation as well as the osteogenic differentiation, together with its underlying mechanisms of action. We showed that DHA enhanced osteogenic differentiation but had no significant effect on hMSCs' proliferation. It probably exerted its functions through the signaling pathways of ERK1/2 as well as Wnt/ß. Because DHA has low toxicity and costs, it might be regarded as an important drug for fracture treatment and tissue engineering.


Assuntos
Artemisininas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , beta Catenina/metabolismo
20.
Medicine (Baltimore) ; 98(34): e16940, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441886

RESUMO

BACKGROUND: The clinical significance of Raman spectroscopy (RS) in colorectal cancer (CRC) patients still remains underestimated. We performed this meta-analysis to elucidate the diagnostic value in CRC patients. METHODS: We systematically searched electronic databases for published articles. Fixed effect model and random effect model were used to calculate the pooled sensitivity, specificity, diagnostic accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and positive posttest probability (PPP) of CRC. Meta-regression and subgroup analysis were conducted to assess potential source of heterogeneity. We also used Egger linear regression tests to assess risk of publication bias. RESULTS: Thirteen studies had been included (679 patients: 186 with premalignant lesions and 493 with malignant lesions). The pooled sensitivity, specificity, diagnostic accuracy, PLR, NLR, DOR and PPP for CRC screening using RS were 0.94 (0.92-0.96), 0.94 (0.88-0.97), 0.96 (0.94-0.98), 16.44 (7.80-34.63), 0.062 (0.043-0.090), 263.65 (99.03-701.96) and 86%, respectively. CONCLUSION: RS is a potentially useful tool for future CRC screening. It also offers potentially early detection for CRC patients.


Assuntos
Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Análise Espectral Raman , Diagnóstico Precoce , Feminino , Humanos , Masculino , Valor Preditivo dos Testes
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