Search

Abstract Heparan sulfate (HS) regulation of FGFR function, which is essential for salivary gland (SG) development, is determined by the immense structural diversity of sulfated HS domains. 3-O-sulfotransferases generate highly 3-O-sulfated HS domains (3-O-HS), and Hs3st3a1 and Hs3st3b1 are enriched in myoepithelial cells (MECs) that produce basement membrane (BM) and are a growth factor signaling hub. Hs3st3a1;Hs3st3b1 double-knockout (DKO) mice generated to investigate 3-O-HS regulation of MEC function and growth factor signaling show loss of specific highly 3-O-HS and increased FGF/FGFR complex binding to HS. During development, this increases FGFR-, BM- and MEC-related gene expression, while in adult, it reduces MECs, increases BM and disrupts acinar polarity, resulting in salivary hypofunction. Defined 3-O-HS added to FGFR pulldown assays and primary organ cultures modulates FGFR signaling to regulate MEC BM synthesis, which is critical for secretory unit homeostasis and acinar function. Understanding how sulfated HS regulates development will inform the use of HS mimetics in organ regeneration.

Abstract Background Severe burns may alter the stability of the intestinal flora and affect the patient’s recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. Methods We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. Results We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. Conclusions Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.

Abstract Preeclampsia (PE) is a significant threat to all pregnancies that is highly associated with maternal mortality and developmental disorders in infants. However, the etiopathogenesis of this condition remains unclear. This study aims to explore the regulatory roles of long noncoding RNAs (lncRNAs) and the mediated competing endogenous RNAs (ceRNA) in the etiopathogenesis of PE through analysis of lncRNA expression patterns in PE and healthy pregnant women (HPW), as well as the construction of lncRNA-mediated ceRNA regulatory networks using bioinformatics. A total of 896 significant differentially expressed lncRNAs, including 586 upregulated lncRNAs and 310 downregulated lncRNAs, were identified in comparison between PE and HPW. Analysis of these differential expressed lncRNAs revealed their predominant enrichment in molecular functions such as sphingosine-1-phosphate phosphatase activity, lipid phosphatase activity, phosphatidate phosphatase activity, thymidylate kinase activity, and UMP kinase activity. Moreover, these differential expressed lncRNAs were predominantly enriched in KEGG analyses such as fat digestion and absorption, lysine degradation, ether lipid metabolism, glycerolipid metabolism, and sphingolipid metabolism. Two ceRNA regulatory networks were constructed based on ceRNA score, including one that had 31 upregulated lncRNAs, 11 downregulated miRNAs, and 34 upregulated mRNAs, while the other contained 128 downregulated lncRNAs, 40 upregulated miRNAs, and 113 downregulated mRNAs. These results may provide a clue to explore the roles of lncRNAs in the etiopathogenesis of PE.

Abstract Background Treatment options for advanced colon cancer are mainly combinations of chemotherapy and targeted drugs. However, poor physical health and medication intolerance limit the choice of anticancer drugs. Colon cancer with cirrhosis is a particular patient group that poses a challenge to clinical treatment. Case presentation This article presents a case of a patient in the decompensated stage of cirrhosis who was diagnosed with advanced colon cancer. The initial presentation was a nodule on his navel named the Sister Mary Joseph’s nodule, which was later confirmed by biopsy and PET-CT as one of the metastases of colon cancer. The patient was treated with cetuximab and 5-fluorouracil at a below-guideline dose; however, portal vein thrombosis developed and led to death. This entire process, from diagnosis to death, occurred within a span of three months. Conclusion Cancers with cirrhosis are a special group that deserves more attention. There is no unified treatment guideline for these patients, especially those with extrahepatic primary tumors. We should be more cautious when choosing treatment for such patients in the future. Both chemotherapy and targeted treatment may potentially induce portal vein thrombosis, which appears to have a higher incidence and worse prognosis than cancers without cirrhosis.

TRAIL (TNF-related apoptosis-inducing ligand) is a potent inducer of tumor cell apoptosis through TRAIL receptors. While it has been previously pursued as a potential anti-tumor therapy, the enthusiasm subsided due to unsuccessful clinical trials and the fact that many tumors are resistant to TRAIL. In this report, we identified heparan sulfate (HS) as an important regulator of TRAIL-induced apoptosis. TRAIL binds HS with high affinity (KD = 73 nM) and HS induces TRAIL to form higher-order oligomers. The HS-binding site of TRAIL is located at the N-terminus of soluble TRAIL, which includes three basic residues. Binding to cell surface HS plays an essential role in promoting the apoptotic activity of TRAIL in both breast cancer and myeloma cells, and this promoting effect can be blocked by heparin, which is commonly administered to cancer patients. We also quantified HS content in several lines of myeloma cells and found that the cell line showing the most resistance to TRAIL has the least expression of HS, which suggests that HS expression in tumor cells could play a role in regulating sensitivity towards TRAIL. We also discovered that death receptor 5 (DR5), TRAIL, and HS can form a ternary complex and that cell surface HS plays an active role in promoting TRAIL-induced cellular internalization of DR5. Combined, our study suggests that TRAIL-HS interactions could play multiple roles in regulating the apoptotic potency of TRAIL and might be an important point of consideration when designing future TRAIL-based anti-tumor therapy.

Heparin is a family of complex carbohydrates binding to proteins to modulate cell activities. Here the authors report the synthesis, and conformations simulations of S-linked hemi-A heparosan [GlcA-S-GlcNAc]n, a thio-glycosidic uncleavable polysaccharide, and test it as human heparanase inhibitor.

IntroductionDysregulated inflammation and coagulation are underlying mechanisms driving organ injury after trauma and hemorrhagic shock. Heparan sulfates, cell surface glycosaminoglycans abundantly expressed on the endothelial surface, regulate a variety of cellular processes. Endothelial heparan sulfate containing a rare 3-O-sulfate modification on a glucosamine residue is anticoagulant and anti-inflammatory through high-affinity antithrombin binding and sequestering of circulating damage-associated molecular pattern molecules. Our goal was to evaluate therapeutic potential of a synthetic 3-O-sulfated heparan sulfate dodecasaccharide (12-mer, or dekaparin) to attenuate thromboinflammation and prevent organ injury.MethodsMale Sprague-Dawley rats were pre-treated subcutaneously with vehicle (saline) or dekaparin (2 mg/kg) and subjected to a trauma/hemorrhagic shock model through laparotomy, gut distention, and fixed-pressure hemorrhage. Vehicle and dekaparin-treated rats were resuscitated with Lactated Ringer’s solution (LR) and compared to vehicle-treated fresh-frozen-plasma-(FFP)-resuscitated rats. Serial blood samples were collected at baseline, after induction of shock, and 3 hours after fluid resuscitation to measure hemodynamic and metabolic shock indicators, inflammatory mediators, and thrombin-antithrombin complex formation. Lungs and kidneys were processed for organ injury scoring and immunohistochemical analysis to quantify presence of neutrophils.ResultsInduction of trauma and hemorrhagic shock resulted in significant increases in thrombin-antithrombin complex, inflammatory markers, and lung and kidney injury scores. Compared to vehicle, dekaparin treatment did not affect induction, severity, or recovery of shock as indicated by hemodynamics, metabolic indicators of shock (lactate and base excess), or metrics of bleeding, including overall blood loss, resuscitation volume, or hematocrit. While LR-vehicle-resuscitated rodents exhibited increased lung and kidney injury, administration of dekaparin significantly reduced organ injury scores and was similar to organ protection conferred by FFP resuscitation. This was associated with a significant reduction in neutrophil infiltration in lungs and kidneys and reduced lung fibrin deposition among dekaparin-treated rats compared to vehicle. No differences in organ injury, neutrophil infiltrates, or fibrin staining between dekaparin and FFP groups were observed. Finally, dekaparin treatment attenuated induction of thrombin-antithrombin complex and inflammatory mediators in plasma following trauma and hemorrhagic shock.ConclusionAnti-thromboinflammatory properties of a synthetic 3-O-sulfated heparan sulfate 12-mer, dekaparin, could provide therapeutic benefit for mitigating organ injury following major trauma and hemorrhagic shock.

Heparan sulfates (HS) contain functionally relevant structural motifs, but determining their monosaccharide sequence remains challenging. Here, the authors develop an ion mobility mass spectrometry-based method that allows unambiguous characterization of HS sequences and structure-activity relationships.

Context Lysionotin, a major extraction of Lysionotus pauciflorus Maxim (Gesneriaceae), has a variety of pharmacological properties commonly used in the treatment of lung disease. A study of lysionotin on the activity of human liver cytochrome P450 (CYP) enzymes can provide guidance on the clinical application of lysionotin. Objective This study investigated the interaction between lysionotin and CYPs. Material and method The effects of 100 μM lysionotin on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific inhibitor as positive control and untreated HLMs as control. Meanwhile, the enzyme kinetic parameters were calculated. A time-dependent study was performed with a time interval of 5 min in 30 min. Results Lysionotin was found to inhibit the activity of CYP3A4, 2C19, and 2C8, with IC50 values of 13.85, 24.95, and 30.05 μM, respectively. The inhibition of CYP3A4 was performed in a non-competitive manner with the Ki value of 6.83 μM, while the inhibition of CYP2C19 and 2C8 was performed in a competitive manner with Ki values of 12.41 and 14.51 μM. Moreover, it was found that the inhibition of CYP3A4 was time-dependent with KI/Kinact value of 6.618/0.048 min/μM. Discussion and conclusions: The in vitro inhibitory effect of lysionotin on the activity of CYP3A4, 2C19, and 2C8 indicated potential drug interactions between lysionotin and drugs metabolised by CYP3A4, 2C19, and 2C8. Further in vivo experiments are needed to assess the potential interactions.

Soil microbial activities are consistently restricted not only by phosphorus availability but also by microbial carbon requirements. Therefore, an incubation experiment was conducted with three soils (QY1, QY2 and QY3) selected on the basis of phosphorus limitation. Results revealed that high N2O emissions, 17.44 µg kg−1, were measured in phosphorus-deficient soil with addition of glucose. In phosphorus-adequate soils, the peaks of N2O emission values in the glucose addition treatment were 20.8 µg kg−1 and 24.7 µg kg−1, which were higher than without glucose-added treatments. CH4 emissions were higher with glucose addition, at 1.9 µg kg−1 in phosphorus-deficient soil and 1.52 µg kg−1 and 2.6 µg kg−1 in two phosphorus-adequate soils. Phosphorus added to deficient and adequate soil significantly increased the cumulative CH4 and N2O emissions compared to the solely glucose added soil and the combination of glucose with phosphorus. Glucose addition significantly increased microbial biomass carbon (MBC) but decreased microbial biomass phosphorus (MBP), especially in the phosphorus-adequate soil. For MBC, the highest value obtained was 175.8 mg kg−1, which was determined under glucose addition in phosphorus-adequate soil. The soil pH increased with glucose addition but decreased with phosphorus addition in phosphorus-deficient soil. The soil organic carbon (SOC) content was significantly affected by glucose addition in the phosphorus-deficient soil. Available phosphorus (AP) was highly influenced by phosphorus addition but did not appear to be affected by glucose addition. From the current study, we concluded that sole phosphorus and glucose addition increase CH4 andN2O emissions in phosphorus-deficient and also in phosphorus-adequate paddy soils. Further study will be conducted on sole and interactive effects of glucose and phosphorous on soil with plants and without plants.

Objective: The role of postoperative radiotherapy (PORT) in resected stage IIIA-N2 non-small cell lung cancer (NSCLC) patients remains controversial. This study aimed to explore the effect of PORT on survival of resected stage IIIA-N2 NSCLC patients.Methods: Resected stage IIIA-N2 NSCLC patients aged 18 years or older were identified from the SEER (Surveillance, Epidemiology, and End Results) database from 2010 to 2015. Cox regression analysis was used to identify factors including PORT associated with survival time. A subgroup analysis of patients stratified by number of lymph node metastases was also performed. Overall survival (OS) and overall mortality were compared among the different groups.Results: A total of 3,445 patients were included in the study. Multivariate Cox analysis showed that PORT had no significant impact on survival of patients with

Liming (L) is a common practice to mitigate soil acidification and enhance soil quality and crop productivity. However, in acidic soil, it is not clear how long-term application of lime and nitrogen (N)-based fertilizer affects soil chemical properties, the wheat and maize grain yields (GY), and N-use efficiency (NUE). Thus, to investigate the effects of N-based fertilizations without L (−L) and with L (+L) on wheat and maize GY and NUE through their effects on soil chemical properties, we analyzed a 28-year field experiment in acidic soil under a wheat-maize system in South China. The analysis was carried out between 1991 and 2010 (before L) and between 2011 and 2018 (after L). We categorized the treatments into (1) no fertilizer (C); nitrogen (N); N and phosphorus (NP); N and potassium (NK); N, P and K (NPK); and NPKCR, NPK and crops residue (CR) applications (NPKCR), before L; and (2) C; N−L; N+L; NP−L; NP+L; NK−L; NK+L; NPK−L; NPK+L; NPKCR−L and NPKCR+L, after L. The effects of long-term fertilization resulted in lower soil pH by 15%, soil available K (AK) by 19%, POlsen by 6%, NO3−-N by 15%, soil organic matter (SOM) by 16%, total N by 16%, and C:N ratio by 13% in −L soil than in +L soil. However, the accumulation of NH4+-N was higher by 40% in −L soil than in +L soil. Wheat and maize GY, N recovery efficiency (REN), and N partial factor productivity (PEPN) were more adversely affected by 8-year fertilizations in −L compared with fertilizations before L and in +L primarily because of the significantly decreased soil pH. Conversely, improvements in wheat and maize yields, REN, and PFPN by 8-year fertilizations in +L were related to increasing soil pH, exchangeable base cations such as Ca2+, Mg2+, and the alleviated toxicity of Al3+. Overall, improvement of GY and NUE from the acidified soil in South China requires the long-term integrated use of fertilizer (NPK), retention of CR, and the +L (i.e., NPKCR+L).

ABSTRACT Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins—a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides. IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.

A long-term field experiment was carried out (since 2008) for evaluating the effects of different substitution rates of inorganic nitrogen (N) fertilizer by green manure (GM) on yield stability and N balance under double rice cropping system. Treatments included, (1) N0 (no N fertilizer and no green manure); (2) N100 (recommended rate of N fertilizer and no green manure); (3) N100-M (recommended rate of N fertilizer and green manure); (4) N80-M (80% of recommended N fertilizer and green manure); (5) N60-M (60% of recommended N fertilizer and green manure); and (6) M (green manure without N fertilization). Results showed that, among all treatments, annual crop yield under N80-M treatment was highest. Crop yield did not show significant differences between N100-M and N80-M treatments. Substitution of different N fertilizer rates by GM reduced the yield variability index. Compared to the N0 treatment, yield variability index of early rice under N100-M, N80-M, and N60-M treatments was decreased by 11%, 26%, and 36%, respectively. Compared to the N0 treatment, yield variability index of late rice was decreased by 12%, 38%, 49%, 47%, and 24% under the N100, N100-M, N80-M, N60-M, and M treatments, respectively. During period of 2009−2013 and 2014−2018, nitrogen recovery efficiency (NRE) was highest under N80-M treatment and N balance was highest under N100 treatment. NRE of all treatments with GM was increased over the time from 2009−2013 to 2014−2018. All treatments with GM showed increasing trend of SOC over the years. Substitution of N fertilizer by GM also increased C inputs and soil C:N ratio compared to the N100 and N0 treatments. Boosted regression model indicated that C input, N uptake and AN were most influencing factors of crop yield. Thus, we concluded that N fertilization rates should be reduced by 20% under GM rotation to attain high yield stability of double rice cropping system through increasing NRE and C inputs.

Land reclamation influences the soil carbon and nitrogen cycling, but its scale and time effects on the balance of soil carbon and nitrogen are still uncertain. Taking the Tarim Basin as the study area, the impact of land reclamation on the soil organic carbon (SOC), total nitrogen (TN), and carbon to nitrogen (C:N) ratio was explored by the multiple temporal changes of land use and soil samples. Remote sensing detected that cropland nearly doubled in area from 1978 to 2015. Spatial analysis techniques were used to identify land changes, including the prior land uses and cultivation ages. Using land reclamation history information, a specially designed soil sampling was conducted in 2015 and compared to soil properties in ca. 1978. Results found a decoupling characteristic between the C:N ratio and SOC or TN, indicating that changes in SOC and TN do not correspond directly to changes in the C:N ratio. The land reclamation history coupled with the baseline effect has opposite impacts on the temporal rates of change in SOC, TN and C:N ratios. SOC and TN decreased during the initial stage of conversion to cropland and subsequently recovered with increasing cultivation time. By contrast, the C:N ratio for soils derived from grassland increased at the initial stage but the increase declined when cultivated longer, and the C:N ratio decreased for soils derived from forest and fluctuated with the cultivation time. Lower C:N ratios than the global average and its decreasing trend with increasing reclamation age were found in newly reclaimed croplands from grasslands. Sustainable agricultural management practices are suggested to enhance the accumulation of soil carbon and nitrogen, as well as to increase the C:N ratio to match the nitrogen deposition to a larger carbon sequestration.

This paper investigates the propagation of Rayleigh surface waves in structures with randomly distributed surface micro-cracks using numerical simulations. The results revealed a significant ultrasonic nonlinear effect caused by the surface micro-cracks, which is mainly represented by a second harmonic with even more distinct third/quadruple harmonics. Based on statistical analysis from the numerous results of random micro-crack models, it is clearly found that the acoustic nonlinear parameter increases linearly with micro-crack density, the proportion of surface cracks, the size of micro-crack zone, and the excitation frequency. This study theoretically reveals that nonlinear Rayleigh surface waves are feasible for use in quantitatively identifying the physical characteristics of surface micro-cracks in structures.

Enoxaparin is a low-molecular weight heparin used to treat thrombotic disorders. Following the fatal contamination of the heparin supply chain in 2007–2008, the U.S. Pharmacopeia (USP) and U.S. Food and Drug Administration (FDA) have worked extensively to modernize the unfractionated heparin and enoxaparin monographs. As a result, the determination of molecular weight (MW) has been added to the monograph as a measure to strengthen the quality testing and to increase the protection of the global supply of this life-saving drug. The current USP calibrant materials used for enoxaparin MW determination are composed of a mixture of oligosaccharides; however, they are difficult to reproduce as the calibrants have ill-defined structures due to the heterogeneity of the heparin parent material. To address this issue, we describe a promising approach consisting of a predictive computational model built from a library of chemoenzymatically synthesized heparin oligosaccharides for enoxaparin MW determination. Here, we demonstrate that this test can be performed with greater efficiency by coupling synthetic oligosaccharides with the power of computational modeling. Our approach is expected to improve the MW measurement for enoxaparin.

Introduction: Dysregulated inflammation and coagulation are underlying mechanisms driving organ injury after trauma and hemorrhagic shock. Heparan sulfates, cell surface glycosaminoglycans abundantly expressed on the endothelial surface, regulate a variety of cellular processes. Endothelial heparan sulfate containing a rare 3-O-sulfate modification on a glucosamine residue is anticoagulant and anti-inflammatory through high-affinity antithrombin binding and sequestering of circulating damage-associated molecular pattern molecules. Our goal was to evaluate therapeutic potential of a synthetic 3-O-sulfated heparan sulfate dodecasaccharide (12-mer, or dekaparin) to attenuate thromboinflammation and prevent organ injury. Methods: Male Sprague-Dawley rats were pre-treated subcutaneously with vehicle (saline) or dekaparin (2 mg/kg) and subjected to a trauma/hemorrhagic shock model through laparotomy, gut distention, and fixed-pressure hemorrhage. Vehicle and dekaparin-treated rats were resuscitated with Lactated Ringer's solution (LR) and compared to vehicle-treated fresh-frozen-plasma-(FFP)-resuscitated rats. Serial blood samples were collected at baseline, after induction of shock, and 3 hours after fluid resuscitation to measure hemodynamic and metabolic shock indicators, inflammatory mediators, and thrombin-antithrombin complex formation. Lungs and kidneys were processed for organ injury scoring and immunohistochemical analysis to quantify presence of neutrophils. Results: Induction of trauma and hemorrhagic shock resulted in significant increases in thrombin-antithrombin complex, inflammatory markers, and lung and kidney injury scores. Compared to vehicle, dekaparin treatment did not affect induction, severity, or recovery of shock as indicated by hemodynamics, metabolic indicators of shock (lactate and base excess), or metrics of bleeding, including overall blood loss, resuscitation volume, or hematocrit. While LR-vehicle-resuscitated rodents exhibited increased lung and kidney injury, administration of dekaparin significantly reduced organ injury scores and was similar to organ protection conferred by FFP resuscitation. This was associated with a significant reduction in neutrophil infiltration in lungs and kidneys and reduced lung fibrin deposition among dekaparin-treated rats compared to vehicle. No differences in organ injury, neutrophil infiltrates, or fibrin staining between dekaparin and FFP groups were observed. Finally, dekaparin treatment attenuated induction of thrombin-antithrombin complex and inflammatory mediators in plasma following trauma and hemorrhagic shock. Conclusion: Anti-thromboinflammatory properties of a synthetic 3-O-sulfated heparan sulfate 12-mer, dekaparin, could provide therapeutic benefit for mitigating organ injury following major trauma and hemorrhagic shock. [ABSTRACT FROM AUTHOR]