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| 2. |
- Han, Xue-Min, et al.
(författare)
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Evolution and Function of the Populus SABATH Family Reveal That a Single Amino Acid Change Results in a Substrate Switch
- 2018
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Ingår i: Plant and Cell Physiology. - : Oxford University Press. - 0032-0781 .- 1471-9053. ; 59:2, s. 392-403
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Tidskriftsartikel (refereegranskat)abstract
- Evolutionary mechanisms of substrate specificities of enzyme families remain poorly understood. Plant SABATH methyltransferases catalyze methylation of the carboxyl group of various low molecular weight metabolites. Investigation of the functional diversification of the SABATH family in plants could shed light on the evolution of substrate specificities in this enzyme family. Previous studies identified 28 SABATH genes from the Populus trichocarpa genome. In this study, we re-annotated the Populus SABATH gene family, and performed molecular evolution, gene expression and biochemical analyses of this large gene family. Twenty-eight Populus SABATH genes were divided into three classes with distinct divergences in their gene structure, expression responses to abiotic stressors and enzymatic properties of encoded proteins. Populus class I SABATH proteins converted IAA to methyl-IAA, class II SABATH proteins converted benzoic acid (BA) and salicylic acid (SA) to methyl-BA and methyl-SA, while class III SABATH proteins converted farnesoic acid (FA) to methyl-FA. For Populus class II SABATH proteins, both forward and reverse mutagenesis studies showed that a single amino acid switch between PtSABATH4 and PtSABATH24 resulted in substrate switch. Our findings provide new insights into the evolution of substrate specificities of enzyme families.
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| 3. |
- Jin, Zhan-Kui, et al.
(författare)
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Outcomes of total knee arthroplasty in the adult Kashin-Beck disease with severe osteoarthritis.
- 2019
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Ingår i: International Orthopaedics. - : Springer. - 0341-2695 .- 1432-5195. ; 43:2, s. 323-331
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and the severe knee pain and functional limitations were seriously affecting the quality of life in patients with end-stage KBD. We retrospectively evaluated the clinical outcomes and the quality of life in KBD patients with total knee arthroplasty (TKA).METHODS: A total of 22 subjects (25 knees) suffered KBD with severe knee pain and underwent primary TKA. Knee pain was measured by visual analogue scale (VAS), and the knee function was evaluated by Knee Society Clinical Rating System Score (KSS). KBD Quality of Life (KBDQOL) was used to evaluate the quality of life in KBD patients before and after TKA.RESULTS: There were no major complications after TKA. The levels of VAS score were obviously deceased in post-operation than that in pre-operation. The levels of KSS score were increased in one year after TKA compared with the pre-operative values, and it maintained a higher level on three years after TKA. The average KBDQOL score level of each domain in pre-operation and one and three years after TKA was increased accordingly. The average scores of physical function, activity limitation, support of society, mental health, and general health in one year after TKA were significantly higher than those in pre-operation.CONCLUSIONS: TKA can reduce knee pain, improve knee function, and improve the quality life in KBD patients. KBDQOL questionnaire may be a promising instrument for assessing the quality life in KBD patients.
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| 4. |
- Sun, Hui-Min, et al.
(författare)
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SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer
- 2016
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Ingår i: American Journal of Cancer Research. - Madison : E-CENTURY PUBLISHING CORP. - 2156-6976. ; 6:8, s. 1636-1649
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Tidskriftsartikel (refereegranskat)abstract
- Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC.
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| 5. |
- Wang, Yi-Ming, et al.
(författare)
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Physiological and transcriptomic analysis provide novel insight into cobalt stress responses in willow
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Cobalt (Co) is an essential component of several enzymes and coenzymes in living organisms. Excess Co is highly toxic to plants. The knowledge of molecular response mechanisms to cobalt stress in plants is still limited, especially in woody plants. The responses of weeping willow (Salix babylonica) seedlings to Co stress were studied using morphological and physiochemical measurements and RNA-seq analysis. The physiological and biochemical indexes such as growth rate, the content of chlorophyll and soluble sugar, photosynthesis and peroxidase activity were all changed in willow seedlings under Co stress. The metal ion concentrations in willow including Cu, Zn and Mg were disturbed due to excess Co. Of 2002 differentially expressed genes (DEGs), 1165 were root-specific DEGs and 837 were stem and leaf-specific DEGs. Further analysis of DEGs showed there were multiple complex cascades in the response network at the transcriptome level under Co stress. Detailed elucidation of responses to oxidative stress, phytohormone signaling-related genes and transcription factors (TFs), and detoxification of excess cellular Co ion indicated the various defense mechanisms in plants respond to cobalt stress. Our findings provide new and comprehensive insights into the plant tolerance to excess Co stress.
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| 6. |
- Wei, Tao, et al.
(författare)
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Molecular and catalytic characterization of a phi class glutathione transferase from Cathaya argyrophylla
- 2012
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Ingår i: Biochemical Systematics and Ecology. - Oxford : Pergamon Press. - 0305-1978 .- 1873-2925. ; 40, s. 75-85
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Tidskriftsartikel (refereegranskat)abstract
- Plant phi class glutathione transferases (GSTs) play important roles in stress tolerance and detoxification metabolism. This study reports the cloning, expression and biochemical characteristics of a phi GST gene (CaGSTF) from the endemic and endangered conifer Cathaya argyrophylla. The recombinant CaGSTF showed GSH-conjugating activity towards the substrate NED-Cl and CDNB. Kinetic analysis revealed low catalytic efficiency with a k(cat)/K-m(GSH) value of 9.82 mM(-1)S(-1). The CaGSTF proved to be a thermolabile enzyme, at 40 degrees C the enzyme's activity was nearly abolished. Site-directed mutagenesis revealed that Ser12, Lys42, Ile55, Glu67 and Ser68 of CaGSTF are critical components of glutathione-binding sites that contribute to the enzyme's catalytic activity. Compared to other plant phi GSTs and conifer tau GSTs, CaGSTF showed a narrow substrate spectrum, low catalytic efficiency and thermolability. These atypical properties suggest the enzyme may have a limited functional role in the organism's adaptation to environmental stresses in the subtropical regions. (C) 2011 Elsevier Ltd. All rights reserved.
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| 7. |
- Chen, Ke-Ling, et al.
(författare)
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Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury
- 2016
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 44:8, s. E664-E677
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
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| 8. |
- Liu, Yong, et al.
(författare)
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Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
- 2017
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Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
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| 9. |
- Liu, Yong, et al.
(författare)
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Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury
- 2016
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : AMER PHYSIOLOGICAL SOC. - 0193-1857 .- 1522-1547. ; 310:5, s. G303-G309
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Tidskriftsartikel (refereegranskat)abstract
- Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.
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| 10. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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