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1.
Mol Biol Cell ; : mbcE19070367, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483737

RESUMO

Ciliary motility depends on both the precise spatial organization of multiple dynein motors within the 96 nm axonemal repeat, and highly coordinated interactions between different dyneins and regulatory complexes located at the base of the radial spokes. Mutations in genes encoding cytoplasmic assembly factors, intraflagellar transport factors, docking proteins, dynein subunits, and associated regulatory proteins can all lead to defects in dynein assembly and ciliary motility. Significant progress has been made in the identification of dynein subunits and extrinsic factors required for pre-assembly of dynein complexes in the cytoplasm, but less is known about the docking factors that specify the unique binding sites for the different dynein isoforms on the surface of the doublet microtubules. We have used insertional mutagenesis to identify a new locus, IDA8/BOP2, required for targeting the assembly of a subset of inner dynein arms to a specific location in the 96 nm repeat. IDA8 encodes FAP57/WDR65, a highly conserved WD repeat, coiled coil domain protein. Using high resolution proteomic and structural approaches, we find that FAP57 forms a discrete complex. Cryo-electron tomography coupled with epitope tagging and gold labeling reveal that FAP57 forms an extended structure that interconnects multiple inner dynein arms and regulatory complexes. Video S1 Video S1 Video of a wild-type cell swimming forward with an asymmetric waveform. Video S2 Video S2 Video of an ida8-1 cell swimming forward with an asymmetric waveform. Video S3 Video S3 Video of a bop2-1 cell swimming forward with an asymmetric waveform. Video S4 Video S4 Video of an ida8-1; Fap57-HA rescued cell swimming forward with an asymmetric waveform. Video S5 Video S5 Video of a bop2-1, FAP57-HA rescued cell swimming forward with an asymmetric waveform. Video S6 Video S6 Video of a pf10 cell swimming with an abnormal waveform. Video S7 Video S7 Video of an ida8-1; pf10 cell swimming with a variable waveform. Video S8 Video S8 Video of a bop2-1; pf10 cell swimming with a variable waveform.

2.
Metab Brain Dis ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31440984

RESUMO

Post-stroke fatigue (PSF) is a common symptom after stroke and interferes with the rehabilitation. There are limited pharmacological therapies for managing PSF. Astragalus membranaceus (Huangqi) is a frequently used Chinese herbal medicine (CHM) in the treatment of fatigue in China. The aim of this review was to summarize the efficacy of adjuvant therapy with CHM Huangqi (CHM-HQ) in managing fatigue after stroke. We searched the databases in both English and Chinese for randomized controlled trials (RCTs) on CHM-HQ for PSF till November 2016. The Cochrane risk of bias tool was used to assess the quality of included trials, and the Review Manager 5.3 software was used to conduct the data analysis. Sixteen RCTs with a total of 1222 participants were included. The evidence was poor in quality with unclear or high risks of bias. Compared to routine intervention, treatment with CHM-HQ decreased the fatigue severity based on the assessment of the Fatigue Severity Scale, Fugl-Meyer and Visual Analogue Scale, and improved the quality of life as measured by the Stroke Specific Quality of Life scale, the Barthel index, and the modified Barthel index, while the adverse effects were mild. In conclusions, adjuvant therapy with CHM-HQ may benefit in managing fatigue and quality of life in stroke patients. However, stronger evidence is needed for a promising conclusion and more rigorous designs of RCTs are merited in the future.

3.
Dent Mater ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31395452

RESUMO

OBJECTIVE: To fabricate a novel nano-hydroxyapatite mineralized silk fibroin (MSF) scaffold in order to diminish the resorption of alveolar ridge and accelerate new bone formation within tooth sockets. Also, to investigate the biocompatibility and osteogenic ability of the MSF in vitro, and the effect of site preservation of the MSF graft in post-extractive sockets in vivo. METHODS: SEM, EDX, FTIR and XRD were used to analyze the mineral crystals deposited on the silk fibroin (SF) surface. Pre-osteoblasts (MC3T3-E1) were seeded on SF and MSF scaffolds. Cell viability, distribution and differentiation were examined using a live-dead assay, histological analysis and Alizarin Red S staining. Furthermore, prepared grafts (SF or MSF scaffold) were implanted into the maxillary right first molar sockets of Sprague Dawley rats for 6 weeks and newly formed bone tissue was analyzed by micro-CT and histological examination. RESULTS: The SEM, EDX, FTIR and XRD analysis demonstrated that granulate nano-hydroxyapatite (nHA) crystals were uniformly distributed on the SF scaffold. In addition, the MSF hydrophilicity measured by water contact angle and swelling ratio was superior to plain SF scaffold. The effect of nHA inorganic crystals on osteogenic differentiation of MC3T3-E1 cells indicated the MSF scaffolds improved osteogenesis. Furthermore, MSF grafts induced more bone formation and reduced the height of alveolar bone resorption after tooth extraction. SIGNIFICANCE: The MSF scaffold partially simulated the structure and composition of natural bone matrix. It induced osteogenic differentiation of MC3T3-E1 cells in vitro, and also promoted new bone regeneration in tooth extraction sockets in vivo, indicating it is a biomaterial with great potential for tooth extraction site preservation.

4.
Molecules ; 24(16)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398934

RESUMO

The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.

5.
Curr Med Sci ; 39(4): 604-608, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346997

RESUMO

Children presenting with partial physeal arrest and significant remaining growth may benefit from physeal bar resection, although the operation is a technique demanding procedure. This study evaluates the treatment of post-traumatic pediatric ankle varus deformity using physeal bar resection and hemi-epiphysiodesis with the assistance of two operative methods. Forty-five patients presenting with a distal tibial medial physeal bridge as well as ankle varus deformity following traumatic ankle physeal injury between 2009 and 2017 were followed. These patients were treated with physeal bar resection and hemi-epiphysiodesis, with the assistance of either fluoroscopy (10 cases) or intraoperative three-dimensional navigation (35 cases). Of the 45 cases, the median age was 9.0 years (range: 3-14 years) with 28 male and 17 female patients. The median of pre-operation ankle varus angle was 20 degrees (IQR 15-25) and 5 degrees (IQR 0-20) at the time of final follow up, representing a statistically significant difference (P<0.05). No differences were observed with regards to age, gender, and surgical history between effective group and ineffective group (P>0.05). The median of pre-operative ankle varus angles of the navigation and fluoroscopy groups were both 20 degrees (P>0.05). The median correction angle of the navigation and fluoroscopy groups was 10 and 15 degrees, respectively (P>0.05). Our results indicate that physeal bar resection and hemiepiphysiodesis are effective treatments for correcting ankle varus deformity due to traumatic medial physeal arrest of the distal tibia. We observe no difference in outcome between fluoroscopy group and three-dimensional navigation group during the procedures.

6.
Obes Surg ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292884

RESUMO

BACKGROUND: Over recent decades, laparoscopic adjustable gastric banding (LAGB) has been among the most common bariatric surgeries. Nowadays, many patients require revision surgery due to insufficient weight loss and band-related complications. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the two most common revision surgeries for failed LAGB, but the conclusions about their efficacy and safety have been inconsistent. This meta-analysis aimed to review the clinical outcomes of SG and RYGB after failed LAGB. METHODS: In accordance with the PRISMA guidelines, the PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for articles that had studied the efficacy and safety of SG and RYGB. The most appropriate effects model was chosen based on the heterogeneity of the articles included in this meta-analysis. Statistical analysis was conducted using Stata 14.0. RESULTS: Of 586 articles that were retrieved, 16 articles which examined 2141 SG and 2990 RYGB patients met the inclusion criteria. The patients in RYGB groups showed increased percent excess weight loss (%EWL) at 12 and 24 months after revision surgery but no statistically significant change was found about %EWL after 3, 6, or 36 months. In addition, RYGB was associated with a higher rate of complications, interventions, and readmission in addition to being of more operative time. CONCLUSIONS: This review suggested that RYGB was more effective at demonstrating weight loss after 12 and 24 months, but comparisons of the long-term efficacy of RYGB with that of SG remain inconclusive. In addition, RYGB was accompanied by a greater number of post-operative complications, interventions, and readmissions. Thus, surgeons should consider the overall status of the patients and their comorbidities as crucial factors when selecting a form of revision surgery. Additional high-quality randomized controlled studies are required to further compare the efficacy and safety of these treatments with longer follow-up times.

7.
Med Sci Monit ; 25: 5263-5271, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31306406

RESUMO

BACKGROUND This study evaluated the imaging features of ganglioneuroma (GN) and assessed the diagnostic value of the enhancement rate (ER) of CT for GN. MATERIAL AND METHODS We retrospectively reviewed records of 49 patients with histopathologically confirmed GN who underwent preoperative contrast-enhanced CT or MRI between 2010 and 2018. The independent samples t test and chi-square test were used. Receiver operating characteristic (ROC) curves were generated to analyze the diagnostic sensitivity (SE) and specificity (SP). Positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS The CT values were 32.59±3.61 Hounsfield units (HU) for plain scans, 38.87±5.09 HU for the arterial phase, and 54.26±8.14 HU for the venous phase, and the incidence of calcification and cysts was 32.6% and 10.2%, respectively. There was no significant difference in CT results and clinical parameters between mediastinal ganglioneuroma (MGN) and retroperitoneal ganglioneuroma (RGN) (p>0.05). The area under the curves (AUCs) for the arterial enhancement rate (AER), venous enhancement rate (VER), and AER/VER combined index in diagnosing GN were 0.735, 0.980, and 0.990, respectively. The VER of 0.2819 exhibited the SE and SP at 92.9% and 92.9%, respectively, to characterize the GN, whereas the AER of 0.1779 had SE and SP of 52.4% and 90.5%, respectively. The SE and SP for the combined index were 88.1% and 100%, respectively. The GN showed hypointensity on T1WI, hyperintense, or slightly high signal on T2WI with the linear hypointensity, and hyperintense on DWI. CONCLUSIONS A hypodense mass was observed for GN on plain scan and presented delayed enhancement on contrast enhancement. VER or AER/VER combination is more accurate than AER for the diagnosis of paravertebral GN.

8.
Dalton Trans ; 48(25): 9152-9160, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31147661

RESUMO

Reactions of an N/Al FLP-based aluminum dihydride (o-TMP-C6H4)AlH2 (1, TMP = N(CMe2CH2)2CH2) with several terminal and internal alkynes were studied. 1 reacted with HC[triple bond, length as m-dash]CR by deprotonated alumination to yield (o-TMP-C6H4)Al(C[triple bond, length as m-dash]CR)2 (R = Ph (2), 1-C4H3S (3)) and with HC[triple bond, length as m-dash]CPPh2 by deprotonated alumination followed by HC[triple bond, length as m-dash]CPPh2 C(sp)-H-activation addition to yield [o-(TMP)H-C6H4]Al(C[triple bond, length as m-dash]CPPh2)3 (4). Furthermore, 1 reacted with R1C[triple bond, length as m-dash]CR2 to produce mono-hydroalumination compounds (o-TMP-C6H4)AlH(CR1[double bond, length as m-dash]CHR2) (R1,R2 = Ph,Ph (5), Ph,Et (6) and SiHMeR',Ph (7, R' = N(SiMe2Ph)-2,6-iPr2C6H3), all as monomers, as well as {(o-TMP-C6H4)AlH[C(PPh2)[double bond, length as m-dash]CHPh]}2 (8), a dimer formed due to the intermolecular P/Al donor-acceptor interaction. Moreover, bis-hydroalumination compounds (o-TMP-C6H4)Al(CR1[double bond, length as m-dash]CHR2)2 (R1,R2 = SiHMe2,PPh2 (9) and SiHPh2,PPh2 (10)) were produced. Natural Bond Orbital (NBO) analysis was performed, which revealed the inequivalent charge distribution on the C[triple bond, length as m-dash]C carbon atoms of the alkynes that have two different substituents. The electronic matching interaction between the Al-H and C[triple bond, length as m-dash]C bonds is discussed. The hydroalumination reaction exhibits the regioselective cis-addition character.

9.
BMC Bioinformatics ; 20(1): 306, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31238875

RESUMO

BACKGROUND: Representation learning provides new and powerful graph analytical approaches and tools for the highly valued data science challenge of mining knowledge graphs. Since previous graph analytical methods have mostly focused on homogeneous graphs, an important current challenge is extending this methodology for richly heterogeneous graphs and knowledge domains. The biomedical sciences are such a domain, reflecting the complexity of biology, with entities such as genes, proteins, drugs, diseases, and phenotypes, and relationships such as gene co-expression, biochemical regulation, and biomolecular inhibition or activation. Therefore, the semantics of edges and nodes are critical for representation learning and knowledge discovery in real world biomedical problems. RESULTS: In this paper, we propose the edge2vec model, which represents graphs considering edge semantics. An edge-type transition matrix is trained by an Expectation-Maximization approach, and a stochastic gradient descent model is employed to learn node embedding on a heterogeneous graph via the trained transition matrix. edge2vec is validated on three biomedical domain tasks: biomedical entity classification, compound-gene bioactivity prediction, and biomedical information retrieval. Results show that by considering edge-types into node embedding learning in heterogeneous graphs, edge2vec significantly outperforms state-of-the-art models on all three tasks. CONCLUSIONS: We propose this method for its added value relative to existing graph analytical methodology, and in the real world context of biomedical knowledge discovery applicability.


Assuntos
Informática/métodos , Conhecimento , Aprendizagem , Algoritmos , Pesquisa Biomédica , Humanos , Redes Neurais (Computação) , Semântica
10.
World Neurosurg ; 129: 345-348, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31233924

RESUMO

BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare low-grade malignant tumor mainly occurring in soft tissues, and its incidence in the bones is extremely rare. Although most of the existing reports focus on the pathological features of AFH, only a few describe its imaging features. To our knowledge, this is the first case of AFH in the skull, and it is distinguished from eosinophilic granuloma based on imaging results. CASE DESCRIPTION: A boy aged 10 years presented with a painless mass of parietal bone after trauma. Cranial computed tomography angiography showed local bone defects near the sagittal suture of the left parietal bone and a soft tissue mass with relatively uniform density in the same area. The signals of this mass were heterogeneous in all sequences of magnetic resonance imaging and presented septal enhancement after the injection of contrast agent. The patient underwent complete resection of the mass, and the histopathological and immunohistochemical diagnosis of the mass was AFH. No complications occurred after the operation and no recurrence occurred during the follow-up. CONCLUSIONS: To our knowledge, this is the first AFH that occured in the skull, and the main imaging manifestations of AFH are bone destruction with soft tissue mass. The characteristic features of AFH are its fibrillar component that showed low signal on T2-weighted imaging and septal or peripheral enhancement, and no dead bone in the mass.

11.
Mol Biol Cell ; 30(15): 1805-1816, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31116684

RESUMO

We previously demonstrated that PACRG plays a role in regulating dynein-driven microtubule sliding in motile cilia. To expand our understanding of the role of PACRG in ciliary assembly and motility, we used a combination of functional and structural studies, including newly identified Chlamydomonas pacrg mutants. Using cryo-electron tomography we show that PACRG and FAP20 form the inner junction between the A- and B-tubule along the length of all nine ciliary doublet microtubules. The lack of PACRG and FAP20 also results in reduced assembly of inner-arm dynein IDA b and the beak-MIP structures. In addition, our functional studies reveal that loss of PACRG and/or FAP20 causes severe cell motility defects and reduced in vitro microtubule sliding velocities. Interestingly, the addition of exogenous PACRG and/or FAP20 protein to isolated mutant axonemes restores microtubule sliding velocities, but not ciliary beating. Taken together, these studies show that PACRG and FAP20 comprise the inner junction bridge that serves as a hub for both directly modulating dynein-driven microtubule sliding, as well as for the assembly of additional ciliary components that play essential roles in generating coordinated ciliary beating.

12.
Ann N Y Acad Sci ; 1448(1): 52-64, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31095746

RESUMO

Coordination between the nervous and innate immune systems to maintain bone homeostasis is largely uncharacterized. The present study investigated the sensory-immune interaction in resting alveolar bone and healing socket by surgical sensory denervation. Bone histomorphometry and immunohistochemistry showed that sensory denervation resulted in moderate suppression of bone remodeling, with a proinflammatory milieu manifested by increased neutrophil recruitment and possible alternations in macrophage phenotypes along the resting bone surface. This denervation effect intensified when bone remodeling was triggered by tooth extraction, as revealed by disrupted temporospatial variations in macrophage subpopulations and neutrophil infiltration, which were closely associated with a dramatic decline in socket bone filling and residual ridge height. Antagonism of calcitonin gene-related peptide (CGRP) brought about similar antianabolic and proinflammatory effects as sensory denervation, suggesting that sensory nerves may monitor the bony milieu by CGRP. Depletion of macrophages, rather than neutrophils, ruled out CGRP effects, illustrating that macrophages were the primary immune mechanism that linked sensory innervation, innate immunity, and bone. The data support that sensory innervation is required for control of innate immune responses and maintenance of bone homeostasis. Sensory neuropeptides, such as CGRP, are a possible target for the development of proanabolic treatments in bone disease by modulating innate immune responses.

13.
Magn Reson Imaging ; 61: 137-142, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31129280

RESUMO

PURPOSE: Only a few studies have investigated the brain morphology abnormalities in structural MRI in patients with drug-naïve idiopathic generalized epilepsy (IGE) and mainly focused on brain volume changes. In the present study, we aimed to investigate the changes in three morphologic measurement differences including cortical thickness, cortical volume, and surface area using FreeSurfer in a pediatric cohort of recent-onset, drug-naïve IGE. METHODS: Forty-five recent-onset, drug-naïve patients diagnosed with IGE and 32 demographically matched healthy controls were recruited. All participants underwent structural MRI scans with a 3.0 T MR system. FreeSurfer, an automated cortical surface reconstruction toolbox, was applied to compare the cortical morphology between patients and controls. The brain regions with significant group differences after multiple comparison correction were extracted in common space for each patient, and then correlated with their clinical characteristics (including onset age, duration of epilepsy, and mini-mental state examination (MMSE)) using partial correlation analysis with age, sex and intracranial volume as covariates. RESULTS: Compared with controls, IGE patients showed decreased cortical thickness in the left rostral middle frontal gyrus, decreased cortical volume in the right cuneus and left superior frontal gyrus that extended to the precentral gyrus, and decreased surface area in the right cuneus and right inferior parietal gyrus. None of these regions showed significant relationships with clinical measurements in the patient group. CONCLUSION: Our findings suggest that cortical thickness, cortical volume, and surface area changes occurred in the early stage of IGE. These findings provide structural neuroimaging evidence underlying the pathology of IGE.

14.
J Invest Surg ; : 1-9, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30885015

RESUMO

PURPOSE: To compare the short-term outcomes between self-expandable metallic stent (SEMS) and decompression tubes (DT) for malignant colorectal obstruction. METHODS: A comprehensive literature search was performed from inception to 2018/12/6 covering Pubmed, Embase, and Cochrane library. Methodological assessments of eligible studies were performed by using Newcastle-Ottawa Scale (NOS). The Revman software (version 5.3) was used in our statistical analysis. RESULTS: Totally 7 cohort studies were enrolled in our meta-analysis. All the 7 eligible studies proved to be high quality according to the NOS scale. Patients receiving SEMS had higher clinical success rates, higher laparoscopic surgery rates, and higher primary anastomosis rates compared with patients receiving DT. CONCLUSIONS: Based on evidence from eastern countries, SEMS placement is an effective procedure that treats malignant colorectal obstruction. Compared with DT placement, patients receiving SEMS may benefit from higher clinical success rates, higher laparoscopic surgery rates, and higher primary anastomosis rates.

15.
Int J Cancer ; 145(5): 1334-1345, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30786019

RESUMO

Oncogenic KRAS is considered a promising target for anti-cancer therapy. However, direct pharmacological strategies targeting KRAS-driven cancers remained unavailable. The prenyl-binding protein PDEδ, a transporter of KRAS, has been identified as a potential target for pharmacological inhibitor by selectively binding to its prenyl-binding pocket, impairing oncogenic KRAS signaling pathway. Here, we discovered a novel PDEδ inhibitor (E)-N'-((3-(tert-butyl)-2-hydroxy-6,7,8,9-tetrahydrodibenzo[b,dfuran-1-yl)methylene)-2,4-dihydroxybenzohydrazide(NHTD) by using a high-throughput docking-based virtual screening approach. In vitro and in vivo studies demonstrated that NHTD suppressed proliferation, induced apoptosis and inhibited oncogenic K-RAS signaling pathways by disrupting KRAS-PDEδ interaction in nonsmall cell lung cancer (NSCLC) harboring KRAS mutations. NHTD redistributed the localization of KRAS to endomembranes by targeting the prenyl-binding pocket of PDEδ and exhibited the suppression of abnormal KRAS function. Importantly, NHTD prevented tumor growth in xenograft and KRAS mutant mouse model, which presents an effective strategy targeting KRAS-driven cancer.

16.
J Cell Biol ; 218(4): 1319-1334, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30808705

RESUMO

Lipid droplets (LDs) serve as cytoplasmic reservoirs for energy-rich fatty acids (FAs) stored in the form of triacylglycerides (TAGs). During nutrient stress, yeast LDs cluster adjacent to the vacuole/lysosome, but how this LD accumulation is coordinated remains poorly understood. The ER protein Mdm1 is a molecular tether that plays a role in clustering LDs during nutrient depletion, but its mechanism of function remains unknown. Here, we show that Mdm1 associates with LDs through its hydrophobic N-terminal region, which is sufficient to demarcate sites for LD budding. Mdm1 binds FAs via its Phox-associated domain and coenriches with fatty acyl-coenzyme A ligase Faa1 at LD bud sites. Consistent with this, loss of MDM1 perturbs free FA activation and Dga1-dependent synthesis of TAGs, elevating the cellular FA level, which perturbs ER morphology and sensitizes yeast to FA-induced lipotoxicity. We propose that Mdm1 coordinates FA activation adjacent to the vacuole to promote LD production in response to stress, thus maintaining ER homeostasis.

17.
Eur J Surg Oncol ; 45(8): 1301-1309, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30738589

RESUMO

OBJECTIVE: Defunctioning stoma (DS) and transanal tube (TT) placement have all been reported to be effective procedures to prevent anastomotic leakage after anterior resection. However, there are few studies that directly compare the 2 procedures, and those that do are unclear. METHODS: We performed a systematic literature search from the databases of Pubmed, Embase and Cochrane library. We limited the publication date from 2008/01/01 to 2018/07/29. The bias risk of eligible randomized controlled trials and cohort studies were assessed by Cochrane Collaboration's tool and Newcastle-Ottawa Scale, respectively. The direct meta-analysis was performed by RevMan 5.3 software. The network graph, inconsistency test and comparison-adjusted funnel plot were performed by the Stata 14.0 software. The indirect meta-analysis and rank probabilities were performed by GeMTC R package. RESULTS: 6 randomized controlled trials and 26 cohort studies were included in our meta-analysis. All eligible studies were assessed as low risk of bias. The anastomotic leakage rate and reoperation rate was lower in the patients receiving DS or TT placement than patients with non-protection. DS shared similar anastomotic leakage rate with TT. However, the reoperation rate was significantly lower in patients receiving DS than patients receiving TT. CONCLUSION: Both TT and DS were protective factors for anastomotic leakage after anterior resection for rectal cancer. DS reduced severity of anastomotic leakage in a more effective way than TT placement. However, we still suggested the routing use of TT for decreasing the risk of anastomotic leakage in anterior resection because it was cheaper and technically simpler.

18.
Microb Cell Fact ; 18(1): 17, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30691455

RESUMO

BACKGROUND: Recombinant human Fibroblast growth factor 21 (rhFGF21) is an endocrine hormone that has profound effects on treatment of metabolic diseases. However, rhFGF21 is prone to form inclusion body when expressed in bacteria, which results in, the downstream process of purification of bioactive rhFGF21 is time-consuming and labor intensive. The aim of this work is to explore a new method for improving the soluble expression and secretion level of rhFGF21 in B. subtilis. RESULTS: A codon optimized rhFGF21 gene was expressed under the control of a strong inducible promoter PmalA in B. subtilis. A mini-cistron cassette (from gsiB) was located upstream of rhFGF21 in expression vector (pMATEFc5), which could reduce the locally stabilized mRNA secondary structure of transcripts and enhance the efficiency of translation initiation. Then various chaperones were further overexpressed to improve the expression efficiency of rhFGF21. Results showed that overexpression of the chaperone DnaK contributed to the increase of solubility of rhFGF21. Moreover, an extracellular proteases deficient strain B. subtilis Kno6cf was used to accumulate the secreted rhFGF21 solidly. In addition, eleven signal peptides from B. subtilis were evaluated and the SPdacB appeared the highest secretion yield of rhFGF21 in B. subtilis. Finally, the combinatorial optimized strain achieved an about ninefold increase of the soluble rhFGF21 production after 24 h of flask fermentation in comparison with the initial production strain. CONCLUSION: This work provided a comprehensive strategy for secretory expressing the heterologous protein rhFGF21 in B. subtilis. To our knowledge, this is the first report of the highly efficient production of rhFGF21 in B. subtilis and this approach may provide some suggestions for heterologous proteins production in B. subtilis.


Assuntos
Bacillus subtilis/metabolismo , Fatores de Crescimento de Fibroblastos/biossíntese , Chaperonas Moleculares/genética , Códon , Fermentação , Fatores de Crescimento de Fibroblastos/genética , Humanos , Regiões Promotoras Genéticas , Sinais Direcionadores de Proteínas , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética
19.
Sci Total Environ ; 650(Pt 2): 2666-2673, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30296774

RESUMO

A field growing/non-growing season asymmetric warming experiment (C: control, i.e., no warming in the entire year; GLNG: growing season warming lower than non-growing season warming; GHNG: growing season warming higher than non-growing season warming) was conducted in an alpine meadow of the Northern Tibetan Plateau in early June 2015. The effects of growing/non-growing season asymmetric warming on the normalized difference vegetation index (NDVI), soil adjusted vegetation index (SAVI), aboveground biomass (AGB) and gross primary production (GPP) in 2015-2017 were examined. The 'GLNG' and 'GHNG' treatments significantly increased the annual mean air temperature (Ta) by 2.95 °C and 2.76 °C, and the vapor pressure deficit (VPD) by 0.23 kPa and 0.28 kPa but significantly reduced the annual mean soil moisture (SM) by 0.02 m3 m-3 and 0.02 m3 m-3 respectively; however, changes in the annual mean Ta, VPD and SM were the same between the 'GLNG' and 'GHNG' treatments over the three years in 2015-2017. There were no significant differences in the SAVI and GPP among the 'C', 'GLNG' and 'GHNG' treatments over the three growing seasons in 2015-2017. The 'GLNG' and 'GHNG' treatments did not significantly affect the NDVI and AGB compared to 'C', whereas the NDVI and AGB under the 'GLNG' treatment were significantly greater than those under the 'GHNG' treatment over the three growing seasons in 2015-2017. The significant differences in NDVI and AGB between the 'GLNG' and 'GHNG' treatments may be attributed to the different effects under the 'GLNG' and 'GHNG' treatments on the non-growing season Ta, growing season water availability and soil nitrogen availability. Therefore, the non-growing season with a higher warming magnitude may have stronger effects on the aboveground plant production than did the growing season with a higher warming magnitude in the alpine meadow of the Northern Tibetan Plateau.


Assuntos
Mudança Climática , Pradaria , Temperatura Alta , Fenômenos Fisiológicos Vegetais , Altitude , Biomassa , Desenvolvimento Vegetal , Estações do Ano , Tibet
20.
J Agric Food Chem ; 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30463403

RESUMO

Bacillus subtilis is widely used for large-scale industrial production of heterologous proteins. Due to its high intrinsic secretory capacity, it can efficiently secrete proteins into the culture supernatant via the general Sec-type secretion pathway. In this study, the α-amylase AmyS was used as a reporter to construct a library encompassing 173 Sec-type signal peptides (SPs) from B. subtilis using a fast, sequence-independent method. The resulting library DNA which harboring different signal peptides in the expression vector was used to transform B. subtilis directly at high efficiency, and 15 SPs which produced a significantly increased yield of AmyS were identified using a starch-iodine based high-throughput assay. Furthermore, the correlation between the sequences of the best-performing signal peptides and their secretion efficiency was analyzed, which revealed several common properties of these SPs. Finally, high-cell-density fermentation of the α-amylase-producing strain with the best-performing signal peptide yielded a maximum of 5086 U/mL amylase at 66 h with a high productivity of 77.1 U/mL·h.

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