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1.
Plant Cell ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051213

RESUMO

Autophagy is known to play an important role in plant-pathogen interactions. Several pathogens including viruses are reported to induce autophagy in plants, but the underpinning mechanism remains largely unclear. Further, in virus-plant interplay it is yet to identify any viral factor(s) responsible for induction of autophagy. Here, we report that ßC1 protein of Cotton leaf curl Multan betasatellite (CLCuMuB) interacts with cytosolic glyceraldehyde-3-phosphate dehydrogenases (GAPCs), a negative autophagic regulator, to induce autophagy in plants. CLCuMuB ßC1 bound to GAPCs and disrupted the interaction between GAPCs and ATG3. A mutant ßC1 protein (ßC13A) in which I45, Y48, and I53 were all substituted with alanine (A), dramatically reduced its binding capacity with GAPCs, failed to disrupt the GAPCs-ATG3 interactions and failed to induce autophagy. Furthermore, mutant virus carrying ßC13A showed increased symptoms and viral DNA accumulation associated with decreased autophagy in plants. These results suggest that CLCuMuB ßC1 activates autophagy by disrupting GAPCs-ATG3 interactions.

2.
Rev Sci Instrum ; 91(1): 015104, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32012536

RESUMO

Image segmentation is a key technique in image analysis for object identification. In this paper, a hybrid segmentation method is proposed, which is based on the Anisotropic Gaussian Kernel (ANGK) edge detector and region adjacent graph (RAG) merging algorithm. An anisotropic directional derivative filter is constructed by angled ANGK to detect the edge contour of original images. Based on the gradient magnitude pattern of the edge contour from ANGK processing, watershed transform is adopted to produce initial partition (coarse segmentation result). Finally, combined with the RAG region merging algorithm, the proposed method performs fine segmentation by merging similar fragmented regions (initial partition) iteratively. Additionally, statistic similarity measure and shape cost function in merging cost are also introduced. They provide quantitative criteria for region merging, which have critical influences on the detection result. A series of experiments are conducted to evaluate the performance of this method, and a preferable localization accuracy as well as noise robustness is proved. Compared with conventional edge and region based methods, the proposed one has a superior segmentation effect. Another advantage is that the problem of oversegmentation can be solved effectively.

3.
Strahlenther Onkol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932995

RESUMO

BACKGROUND AND OBJECTIVE: The magnitude of intra-fractional prostate displacement (change from initial position over time) is associated with the duration of the patient lying on the radiotherapy treatment couch. This study reports a minute-by-minute association and calculates the impact of this displacement on duration-dependent margins using real-time intra-fractional position data monitored by four-dimensional transperineal ultrasound (4D TPUS). MATERIALS AND METHODS: A total of 55 patients were recruited prospectively. Intra-fractional position of the prostate was monitored in real-time using a 4D TPUS Clarity® system. A total of 1745 monitoring sessions were analysed. Van Herk's margin recipe (2.5∑ + 1.64((σ2 + σp2)1/2 - σp)) was used to estimate the duration-dependant margins for every minute, up to the 15th minute. Linear regression analysis was then performed on the overall margins against time and direction. RESULTS: The mean intra-fractional position was 0.76 mm Inferior (Inf), 0 mm Lateral (Lat) and 0.94 mm Posterior (Post) at the 15th minute. A minimum margin expansion of 2.42 mm (Superior/Inf), 1.02 mm (Left/Right) and 2.65 mm (Anterior/Post) was required for an 8­minute treatment compared to 4.29 mm (Sup/Inf), 1.84 mm (Lt/Rt) and 4.63 mm (Ant/Post) for a 15-minute treatment. The required margin expansion increased linearly (R2 = 0.99) in all directions (p < 0.01). However, while there was no statistically significant difference (p = 0.10) in the required margin expansion in the Sup/Inf and Ant/Post directions respective of the time duration, the margins were much bigger compared to those in the Lt/Rt direction (p < 0.01). CONCLUSION: We report our experience in deriving the minimum duration-dependant margin to generate the required planning target volume for prostate radiotherapy. The required margin increases linearly in all directions within the 15-min duration; thus, the margin will depend on the duration of the technique chosen (IMRT/VMAT/3DCRT/proton).

4.
Expert Rev Anti Infect Ther ; : 1-9, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31971031

RESUMO

Introduction: Two billion population are at risk of dengue fever and by 2080, over six billion population will be at risk. Hepatitis is common in dengue and the liver is invariably involved in severe cases. We conducted a literature review using the PubMed database on articles covering a broad range of issues related to dengue and hepatitis.Areas covered: This article overviews available literature on changes in the definition of severe dengue, pathogenesis of liver involvement in dengue, clinical manifestations, and predictors of mortality in severe dengue with liver involvement, impact of viral hepatitis co-infections and hepatotoxic drugs, and hemophagocytic lymphohistiocytosis.Expert commentary: Hepatitis is commonly seen in dengue however the degree of elevation of transaminases did not correlate well with severity of illness in observational studies, except in the elderly. The underlying pathogenesis of liver injury is still being elucidated and further studies are required to fully understand the cellular pathways. Acute or chronic viral hepatitis does not appear to affect dengue outcomes. Commonly used medications such as paracetamol and statins may influence dengue outcomes.

5.
CNS Neurosci Ther ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943833

RESUMO

AIMS: Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin - (Ang -)-induced CSVD were evaluated. METHODS: To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang -, and NR was added to the food of the mice for 28 days. Then, short-term memory, blood-brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated. RESULTS: Our data showed that mice infused with Ang - exhibited decreased short-term memory function and BBB leakage due to decreased claudin-5 expression and increased caveolae-mediated endocytosis after 28 days. Furthermore, Ang - decreased the expression of α-smooth muscle actin (α-SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD-related damages induced by Ang - were inhibited by NR administration. Moreover, NR administration significantly reduced glial activation around the vessels. CONCLUSION: Our results indicated that NR administration alleviated Ang --induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)-associated cognitive impairment.

6.
Interact Cardiovasc Thorac Surg ; 30(2): 303-311, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642911

RESUMO

OBJECTIVES: The aim of this study was to establish an original transapical septal myectomy procedure that can be performed in the beating heart via a minimally invasive approach for the treatment of hypertrophic obstructive cardiomyopathy. METHODS: We designed an original intracardiac septum resection device to conduct off-pump septal myectomy in swine. A subxiphoid minithoracotomy was performed to access the apex of the heart. This resection device was inserted into the left ventricular outflow tract of the heart via the apex. The basal anteroseptal myocardium beneath the right aortic cusp was identified using a combination of transoesophageal and transthoracic echocardiography and then resected and collected by the device. RESULTS: Six consecutive operations were successfully and accurately performed using the custom-made device under echocardiographic guidance. All pigs survived and appeared to be normal until planned euthanasia 1 week after operation. A 300-700 mg portion of the septal myocardium was resected from the normal swine heart. Echocardiography and electrocardiogram revealed no abnormalities after resection. One exception was the fifth pig, in which mild annular regurgitation of the aortic valve occurred after repetitive resection. Postmortem necropsy demonstrated that all resections were correctly located at the basal anteroseptal septum beneath the right aortic cusp. CONCLUSIONS: Our study provides the first proof-of-concept evidence for a novel beating heart transapical septal myectomy procedure, which showed promising translational potential for the treatment of hypertrophic obstructive cardiomyopathy. This procedure would probably reduce operative risks and improve outcomes and reduce the demanding expertise required to perform conventional surgical myectomy.

7.
PLoS One ; 14(12): e0225247, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31825954

RESUMO

BACKGROUND: Epidemiological studies have shown that gastrointestinal Helicobacter pylori (H. pylori) infection is the main cause of chronic gastritis, but the relation between oral H. pylori and chronic periodontitis (CP) remains uncertain. A meta-analysis of published papers was performed to elucidate the correlation between oral H. pylori and CP. METHOD: To perform this meta-analysis, we searched papers published from 2000 to 2018 on PubMed, OVID, Springer Link, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biology Medicine search engines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the correlation between H. pylori and CP were estimated. Heterogeneity, publication bias and subgroup analyses were also conducted. RESULTS: A total of 918 papers on oral H. pylori and CP were collected, and 11 papers were in accordance with the inclusion criteria. Oral H. pylori was suggested to be correlated with CP. The results indicated that a H. pylori-positive state significantly increased the risk of CP 3.42 times (OR = 3.42; 95% CI = 2.71-4.31). A diagnostic test using polymerase chain reaction (PCR) showed a higher prevalence of H. pylori (OR = 3.70; 95% CI = 2.66-5.14) than did that using the rapid urease test (RUT) (OR = 3.13; 95% CI = 2.26-4.34). CONCLUSIONS: This paper demonstrated that CP was potentially correlated with oral H. pylori in adults and that oral H. pylori may be a possible risk factor for CP.

8.
Breast ; 49: 165-170, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31812892

RESUMO

AIM: To determine whether the addition of regional nodal irradiation (RNI) to whole-breast irradiation (WBI) would improve outcomes over WBI alone in T1-2N1 breast cancer after breast-conserving surgery (BCS) and adjuvant systematic therapy. METHODS: Data were obtained from two randomized controlled trials (NCT00174655 and NCT00312208). Univariate and multivariate Cox-regression analysis were performed to investigate predictors for overall survival and disease-free survival. A 1:1 propensity score matching (PSM) analysis was applied to eliminate selection bias. RESULTS: With median follow-up 80 months (range: 3-155 months), the 5-year local regional recurrence in the WBI group was 2% vs. 5% (p = 0.28) in the WBI + supraclavicular radiotherapy, and the rate of 5-year distant metastasis in the WBI group was 7% vs. 13% in the WBI + supraclavicular radiotherapy (p = 0.0748); In addition, the 5-year local regional recurrence in the WBI group was 3% vs. 9% (p = 0.19) in the WBI + internal mammary irradiation (IMI); However, the rate of 5-year distant metastasis in the in the WBI group was significantly lower than that in the WBI + IMI (8% vs. 24%, p = 0.036). After PSM, cox-regression analysis indicated that neither RNI nor IMI in combination with WBI in T1-2N1 breast cancer was associated with an improved overall survival and disease-free survival when compared to WBI alone. CONCLUSION: The addition of RNI to WBI in T1-2N1 breast cancer after BCS and adjuvant systematic therapy did not improve outcomes in comparison with WBI alone. Further studies are still needed to identify patients who would most benefit from RNI in this patient population.

9.
PLoS Pathog ; 15(12): e1008199, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31815960

RESUMO

More than half of the world population is at risk of dengue virus (DENV) infection because of the global distribution of its mosquito vectors. DENV is an envelope virus that relies on host lipid membranes for its life-cycle. Here, we characterized how DENV hijacks the mosquito lipidome to identify targets for novel transmission-blocking interventions. To describe metabolic changes throughout the mosquito DENV cycle, we deployed a Liquid chromatography-high resolution mass spectrometry (LC-HRMS) workflow including spectral similarity annotation in cells, midguts and whole mosquitoes at different times post infection. We revealed a major aminophospholipid reconfiguration with an overall early increase, followed by a reduction later in the cycle. We phylogenetically characterized acylglycerolphosphate acyltransferase (AGPAT) enzyme isoforms to identify those that catalyze a rate-limiting step in phospholipid biogenesis, the acylation of lysophosphatidate to phosphatidate. We showed that DENV infection decreased AGPAT1, but did not alter AGPAT2 expression in cells, midguts and mosquitoes. Depletion of either AGPAT1 or AGPAT2 increased aminophospholipids and partially recapitulated DENV-induced reconfiguration before infection in vitro. However, only AGPAT1 depletion promoted infection by maintaining high aminophospholipid concentrations. In mosquitoes, AGPAT1 depletion also partially recapitulated DENV-induced aminophospholipid increase before infection and enhanced infection by maintaining high aminophospholipid concentrations. These results indicate that DENV inhibition of AGPAT1 expression promotes infection by increasing aminophospholipids, as observed in the mosquito's early DENV cycle. Furthermore, in AGPAT1-depleted mosquitoes, we showed that enhanced infection was associated with increased consumption/redirection of aminophospholipids. Our study suggests that DENV regulates aminophospholipids, especially phosphatidylcholine and phosphatidylethanolamine, by inhibiting AGPAT1 expression to increase aminophospholipid availability for virus multiplication.

10.
Exp Ther Med ; 18(6): 4379-4387, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31777542

RESUMO

Crucial to the development and maintenance of pain sensations is neurotrophin receptor p75 (p75NTR), the low affinity receptor of brain-derived neurotrophic factor (BDNF). This receptor is widespread among dorsal root ganglion (DRG) neurons and the spinal cord. Few reports have demonstrated the specific role of p75NTR in the development of cancer-induced bone pain (CIBP). Therefore the present study examined whether p75NTR contributed to CIBP by upregulating mammalian target of rapamycin (mTOR) signaling. A CIBP rat model was induced and reverse transcription-quantitative polymerase chain reaction was employed to determine p75NTR and mTOR mRNA expression. Immunofluorescence analysis was performed to determine the coexpression of p75NTR and mTOR in DRG neurons, as well as the spinal cord. Von Frey filaments were used to measure the 50% likelihood of paw withdrawal thresholds (PWTs). Spontaneous pain was assessed by ambulatory score. The results demonstrated that compared with the control group, mTOR activation in primary cultured DRG neurons was significantly increased. In addition, mTOR and p75NTR expression was significantly enhanced in the BDNF-treated primary DRG in the BDNF group. In vivo experiments determined that mTOR and p75NTR levels were increased in the CIBP rats compared with the sham group. PWT, in response to mechanical stimulation, was significantly lower compared with that in sham rats and the ambulatory score was significantly higher than that in sham rats. Finally, intrathecal injection of a p75NTR-targeting small interfering RNA significantly decreased mTOR and p75NTR expression levels in DRG neurons and the spinal cord of CIBP rats, as well as partially reversing the decline in PWTs and the increase in ambulatory score. In conclusion, the present study determined that the activation of BDNF/p75NTR/mTOR signaling may participate in nociceptive transmission in CIBP, suggesting a novel mechanism and potential therapeutic target for CIBP treatment and management.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31628626

RESUMO

A Gram-stain negative, non-motile, asporogenous, aerobic and rod-shaped bacterial strain, designated ZY113T, was isolated from the surface of a marine red alga collected from the coast in Weihai, Shandong Province, China. Strain ZY113T was found to grow at 4-37 °C (optimum at 28-30 °C), with 1.0-7.0% (w/v) NaCl (optimum 2.0-3.0%) and at pH 6.0-9.0 (optimum 7.0-8.0). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ZY113T is a member of the genus Polaribacter, with Polaribacter dokdonensis KCTC 12392T as a close relative (97.4% similarity). The sole respiratory quinone was found to be menaquinone 6 (MK-6) and the major fatty acids were identified as iso-C15:0, iso-C15:0 3-OH and iso-C13:0. The polar lipids were found to consist of phosphatidylethanolamine, two unidentified aminolipids and three unidentified lipids. The G + C content of the genomic DNA was determined to be 30.1 mol%. On the basis of phenotypic, genotypic and phylogenetic analysis, strain ZY113T is considered to represent a novel species of the genus Polaribacter, for which the name Polaribacter aquimarinus sp. nov. is proposed. The type strain is ZY113T (= KCTC 62374T = MCCC 1H00296T).

12.
PLoS Biol ; 17(10): e3000461, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600191

RESUMO

Dendritic spine development is crucial for the establishment of excitatory synaptic connectivity and functional neural circuits. Alterations in spine morphology and density have been associated with multiple neurological disorders. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. However, the role of DIP2A in the brain remains largely unknown. In this study, we found that deletion of Dip2a in mice induced defects in spine morphogenesis along with thin postsynaptic density (PSD), and reduced synaptic transmission of pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. Furthermore, Dip2a knockout (KO) mice exhibited autism-like behaviors, including excessive repetitive behaviors and defects in social novelty. Importantly, acetylation mimetic cortactin restored the impaired synaptic transmission and ameliorated repetitive behaviors in these mice. Altogether, our findings establish an initial link between DIP2A gene variations in autism spectrum disorder (ASD) and highlight the contribution of synaptic protein acetylation to synaptic processing.

13.
BMC Infect Dis ; 19(1): 859, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623569

RESUMO

BACKGROUND: Tuberculosis (TB) remains one of the infectious diseases with a leading cause of death among adults worldwide. Metformin, a first-line medication for the treatment of type 2 diabetes, may have potential for treating TB. The aims of the present systematic review were to evaluate the impact of metformin prescription on the risk of tuberculosis diseases, the risk of latent TB infection (LTBI) and treatment outcomes of tuberculosis among patients with diabetic mellitus. METHODS: Databases were searched through March 2019. Observational studies reporting the effect of metformin prescription on the risk and treatment outcomes of TB were included in the systematic review. We qualitatively analyzed results of included studies, and then pooled estimate effects with 95% confidence intervals (CIs) of different outcome using random-effect meta-analyses. RESULTS: This systematic review included 6980 cases from 12 observational studies. The meta-analysis suggested that metformin prescription could decrease the risk of TB among diabetics (pooled odds ratio [OR], 0.38; 95%CI, 0.21 to 0.66). Metformin prescription was not related to a lower risk of LTBI (OR, 0.73; 95%CI, 0.30 to 1.79) in patients with diabetes. Metformin medication during the anti-tuberculosis treatment is significantly associated with a smaller TB mortality (OR, 0.47; 95%CI, 0.27 to 0.83), and a higher probability of sputum culture conversion at 2 months of TB disease (OR, 2.72; 95%CI, 1.11 to 6.69) among patients with diabetes. The relapse of TB was not statistically reduced by metformin prescription (OR, 0.55; 95%CI, 0.04 to 8.25) in diabetics. CONCLUSIONS: According to current observational evidence, metformin prescription significantly reduced the risk of TB in patients with diabetes mellitus. Treatment outcomes of TB disease could also be improved by the metformin medication among diabetics.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Tuberculose/patologia , Antituberculosos/uso terapêutico , Humanos , Razão de Chances , Fatores de Risco , Escarro/microbiologia , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade
14.
Future Oncol ; 15(30): 3503-3511, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31580147

RESUMO

Aim: To investigate the risk factors for developing osteonecrosis of jaw (ONJ) in advanced cancer patients with bone metastases underwent zoledronic acid (ZA) treatment. Materials & methods: Univariate and multivariate logistic regression analyses were performed to investigate factors associated with developing ONJ in advanced cancer patients. Results: A total of 2214 advanced cancer patients were included. Univariate and multivariate logistic regression analyses for risk factors associated with ONJ were older age (≥66 years, hazards ratio [HR]: 3.21; p = 0.007), anemia (HR: 3.29; p = 0.006) and duration of ZA exposure (between 1 and 2 years, HR: 3.91, p = 0.01; ≥2 years, HR: 8.07, p < 0.001), respectively. Conclusion: Patients with older age, anemia and/or more than 1 year of ZA treatment are at high risk of developing ONJ.

15.
World J Gastroenterol ; 25(36): 5483-5493, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576094

RESUMO

BACKGROUND: Primary hepatocellular carcinoma (HCC) is a very malignant tumor in the world. CARMA3 plays an oncogenic role in the pathogenesis of various tumors. However, the function of CARMA3 in HCC has not been fully clarified. AIM: To study the biological function of CAEMA3 in HCC. METHODS: Tissue microarray slides including tissues form 100 HCC patients were applied to access the expression of CARMA3 in HCC and its clinical relevance. Knockdown and overexpression of CARMA3 were conducted with plasmid transfection. MTT, colony formation, and apoptosis assays were performed to check the biological activity of cells. RESULTS: Higher expression of CARMA3 in HCC was relevant to poor prognostic survival (P < 0.05). Down-regulation of CARMA3 inhibited proliferation and colony formation and induced apoptosis in HCC cell lines, while increasing its expression promoted tumorigenesis. We also found that sodium aescinate (SA), a natural herb extract, exerted anti-proliferation effects in HCC cells by suppressing the CARMA3/nuclear factor kappa-B (NF-κB) pathway. CONCLUSION: Overexpression of CARMA3 in HCC tissues correlates with a poor prognosis in HCC patients. CARMA3 acts pro-tumorigenic effects partly through activation of CARMA3/NF-κB. SA inhibits HCC growth by targeting CARMA3/NF-κB.

16.
Hepatology ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31529495

RESUMO

BACKGROUND AND AIMS: Although knowledge regarding the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has profoundly grown in recent decades, the internal restrictive mechanisms remain largely unknown. We have recently reported that the transcription repressor interferon regulatory factor-2 binding protein 2 (IRF2BP2) is enriched in cardiomyocytes and inhibits pathological cardiac hypertrophy in mice. Notably, IRF2BP2 is abundantly expressed in hepatocytes and dramatically down-regulated in steatotic livers, whereas the role of IRF2BP2 in NAFLD is unknown. APPROACH AND RESULTS: Herein, using gain-of-function and loss-of-function approaches in mice, we demonstrated that while hepatocyte-specific Irf2bp2 knockout exacerbated high-fat diet-induced hepatic steatosis, insulin resistance and inflammation, hepatic Irf2bp2 overexpression protected mice from these metabolic disorders. Moreover, the inhibitory role of IRF2BP2 on hepatosteatosis is conserved in a human hepatic cell line in vitro. Combinational analysis of digital gene expression and chromatin immunoprecipitation sequencing identified activating transcription factor 3 (ATF3) to be negatively regulated by IRF2BP2 in NAFLD. Chromatin immunoprecipitation and luciferase assay substantiated the fact that IRF2BP2 is a bona fide transcription repressor of ATF3 gene expression via binding to its promoter region. Functional studies revealed that ATF3 knockdown significantly relieved IRF2BP2 knockout-exaggerated hepatosteatosis in vitro. CONCLUSION: IRF2BP2 is an integrative restrainer in controlling hepatic steatosis, insulin resistance, and inflammation in NAFLD through transcriptionally repressing ATF3 gene expression.

17.
Phys Rev E ; 100(1-1): 010402, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31499827

RESUMO

We propose a computational method to quantitatively evaluate the systematic uncertainties that arise from undetectable sources in biological measurements using live-cell imaging techniques. We then demonstrate this method in measuring the biological cooperativity of molecular binding networks, in particular, ligand molecules binding to cell-surface receptor proteins. Our results show how the nonstatistical uncertainties lead to invalid identifications of the measured cooperativity. Through this computational scheme, the biological interpretation can be more objectively evaluated and understood under a specific experimental configuration of interest.


Assuntos
Imagem Molecular , Incerteza , Sobrevivência Celular , Modelos Estatísticos
18.
Mol Med Rep ; 20(4): 3802-3810, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485625

RESUMO

Glial cell line­derived neurotrophic factor (GDNF) is critical for the proliferation of spermatogonial stem cells (SSCs), but the underlying mechanisms remain poorly understood. In this study, an unbiased metabolomic analysis was performed to examine the metabolic modifications in SSCs following GDNF deprivation, and 11 metabolites were observed to decrease while three increased. Of the 11 decreased metabolites identified, glycylglycine was observed to significantly rescue the proliferation of the impaired SSCs, while no such effect was observed by adding sorbitol. However, the expression of self­renewal genes, including B­cell CLL/lymphoma 6 member B, ETS variant 5, GDNF family receptor α1 and early growth response protein 4 remained unaltered following glycylglycine treatment. This finding suggests that although glycylglycine serves an important role in the proliferation of SSCs, it is not required for the self­renewal of SSCs.

19.
Mar Drugs ; 17(9)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470535

RESUMO

Four new (penigrisacids A-D, 1-4) and one known (5) carotane sesquiterpenoids were isolated from the deep-sea-derived fungus Penicillium griseofulvum, along with four known compounds (6-9). The planar structures and relative configurations of the new compounds were determined by extensive analysis of the NMR and HRESIMS data. The absolute configurations were established by comparison of the experimental and calculated ECD (electronic circular dichroism) spectra or OR (optical rotation) value. Compound 9 exhibited potent anti-food allergic activity with IC50 value of 28.7 µM, while 4 showed weak cytotoxicity against ECA-109 tumor cells (IC50 = 28.7 µM).


Assuntos
Organismos Aquáticos/química , Penicillium/química , Sesquiterpenos/química , Linhagem Celular Tumoral , Dicroísmo Circular , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética/métodos , Oceanos e Mares , Sesquiterpenos/farmacologia
20.
Biomed Pharmacother ; 117: 109204, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387177

RESUMO

We wished to investigate the role of a tilapia skin collagen polypeptide (TSCP; molecular weight <3 kDa) in alleviating liver and kidney injuries in aging mice induced by d-galactose (d-gal) and its underlying mechanism of action. First, we characterized TSCP. TSCP was passed through a 3-kDa ultrafiltration membrane, desalted in water by a solid-phase extraction column, purified further by reverse phase-high performance liquid chromatography, and analyzed by electrospray ionization mass spectrometry and tandem mass spectrometry. TSCP contained 17 types of amino acids (AAs) and 41 peptide chains of length 7 AAs to 22 AAs. The content of free AAs and total AAs of TSCP was 13.5% and 93.79%, respectively. Next, we undertook animal experiments. Mice were injected once-daily with D-gal (300 mg/kg body weight, s.c.) for 8 weeks, and TSCP was administered simultaneously once-daily by intragastric gavage. TSCP could visibly improve the decreased body weight, depressed appetite, and mental deterioration of mice triggered by d-gal. TSCP could also alleviate d-gal-induced damage to the liver and kidneys according to histopathology (especially high-dose TSCP). Consistent with these macroscopic and pathologic changes, TSCP could also prevent d-gal-induced increases in serum levels of alanine aminotransferase, aspartate transaminase, alkaline phosphatase, lipid peroxidation, creatinine and uric acid, as well as decreases in serum levels of immunoglobulin (Ig)G and IgM. Moreover, TSCP improved the activities of superoxide dismutase, catalase, and glutathione peroxidase, but also inhibited the increases in the levels of malondialdehyde and inducible nitric oxide synthase expression in the liver and kidneys of d-gal-treated mice. These results suggest that TSCP can alleviate the injuries to the liver and kidneys in aging mice induced by d-gal, and that its mechanism of action might be, at least partially, associated with attenuation of oxidative stress and enhancement of immune function.


Assuntos
Colágeno/farmacologia , Galactose/efeitos adversos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Tilápia/metabolismo , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
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