Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunb...Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunbergii and appraised their LMPST on palmitic acid(PA)induced lipid accretion in Hep G2,and 3T3-L1 cells.LMPST treatment lessened lipid deposition and intracellular free fatty acid and triglyceride intensities in PA-treated above mentioned cells.The mechanistic study publicized that LMPST2 significantly suppressed adipogenesis and stimulated the PA-treated 3T3-L1 cells occupied in the lipolysis pathway.Furthermore,in PA-treated Hep G2 cells,the free fatty acid oxidation was significantly increased by LMPST2.Given these constructive properties of LMPST2 from S.thunbergii,is a potential candidate for diminishing the intracellular lipids,and for a therapeutic agent in those conditions.展开更多
The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate ki...The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate kidney dysfunction in chronic kidney diseases and inhibit diabetic vascular complications.In many studies,LMWF was found to be more potent than fucoidan with high molecular weight.However,the pharmacokinetics of LMWF still remains unclear.The purpose of the research is to compare the pharmacokinetics of fucoidan with high molecular weight(136 kDa)with that low molecular weight(9.5 kDa)after oral administration to ICR mice.Since fucose is the main and representative monosaccharide of fucoidans,we evaluate the pharmacokinetics of fucoidan and LMWF by determining the fucose concentration in mice serum.Both fucoidan and LMWF were absorbed following oral administration.Fucoidan and LMWF were provided to mice by oral administration with 60 mg/kg and the maximum Concentration(C_(max))was found at 2.5 h(0.66±0.32 mg/L)for Fucoidan and 1.5 h(1.01±0.56 mg/L)for LMWF,respectively.It seems that LMWF had a higher area under the curve(AUC_(0–t))and was absorbed more quickly than fucoidan.The estimated bioavailability of LMWF was28.3%in the mice treated with a single dose of 30 mg/kg.In addition,LMWF was found widely spreaded into different tissues following oral administration and the highest concentration was found in kidney at 19.93±7.02μg/g.In this study,we first studied the pharmacokinetics of LMWF,in order to help to understand the function of LMWF.And our results shed light on the potential of development of drugs based on LMWF.展开更多
As one of the most important cereals,wheat(Triticum aestivum)has high nutritional value and is widely cultivated in China.However,wheat can cause severe allergic reactions,and a growing number of people are developing...As one of the most important cereals,wheat(Triticum aestivum)has high nutritional value and is widely cultivated in China.However,wheat can cause severe allergic reactions,and a growing number of people are developing allergies to Chinese wheat.Low molecular weight glutenin(LMW-GS),an important allergen in susceptible populations,is responsible for celiac disease and wheat contacts dermatitis.In this study,LMW-GS was highly purified from Chinese wheat(Xiaoyan 6)and further identified and characterized.In addition,8 peptides were predicted efficiently by 5 immunological tools,among which 5 peptides showed significant immunoglobulin E binding abilities.Two specific epitopes were found to be in the non-conserved region of the amino acid sequence of LMW-GS,which was speculated to be the specific epitope of Chinese wheat.This systematic research of LMW-GS may provide new insights into the prevention of wheat allergy and development of hypoallergenic wheat products.展开更多
BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulat...BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulation treatment have an associated increase rate.GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants(DOAC),especially with active cancer therapies.AIM To evaluate patient risk factors,effectiveness(VTE)and safety(MB)of DOACs and low molecular weight heparin(LMWH)in patients with active GICA-VTE.METHODS A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed.Inclusion criteria included active GI cancer diagnosed at any stage or treatment+/-6 mo of VTE diagnosis,whom were prescribed 6 mo or more of DOACs or LMWH.The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events.Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTS A total of 144 patients were prescribed anticoagulation,in which 106 fulfilled inclusion criteria apixaban(27.3%),rivaroxaban(34.9%)and enoxaparin(37.7%),and 38 were excluded.Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event,with 62%males,80%Caucasian,70%stage IV,pancreatic cancer(40.5%),30%Khorana Score(≥3 points),and 43.5%on active chemotherapy.Sixty-four percent of patients completed anticoagulation therapy(range 1 to 43 mo).Recurrent VTE at 6 mo was noted in 7.5%(n=3),6.8%(n=2)and 2.7%(n=1)of patients on enoxaparin,apixaban and rivaroxaban,respectively(all P=NS).MB at 6 mo were 5%(n=2)for enoxaparin,6.8%(n=2)for apixaban and 21.6%(n=8)for rivaroxaban(overall P=0.048;vs LMWH P=0.0423;all other P=NS).Significant predictors of a primary or secondary outcome for all anticoagulation therapies included:Active systemic treatment(OR=5.1,95%CI:1.3-19.3),high Khorana Score[≥3 points](OR=5.5,95%CI:1.7-17.1),active smoker(OR=6.7,95%CI:2.1-21.0),pancreatic cancer(OR=6.8,95%CI:1.9-23.2),and stage IV disease(OR=9.9,95%CI:1.2-79.1).CONCLUSION Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.展开更多
Incubation experiments were conducted to investigate the dynamics of low- molecufar-weight aliphatic acids in two andosols with and without plant materials. Results showed that amount of low- molecular-weight aliphati...Incubation experiments were conducted to investigate the dynamics of low- molecufar-weight aliphatic acids in two andosols with and without plant materials. Results showed that amount of low- molecular-weight aliphatic acids in soils alone varied considerably with water regime under which the soil was incubated,duration of incubation and soil organic matter content, ranging from 257-860 pmol kg-1 soil I of which 19%～33% was in free state. Incorporation of plant materials increased greatly both the amount and number of members of low- molecular- weight aliphaticacidst and also the proporticn of low-molec "far-weight aliphatic acids occurred in free state. Generally, among these aliphatic acids detected, acetic, propionic, glyoxalic and formic acids were predominant.展开更多
Low-molecular-weight (LMW) organic acids exist widely in soils and play an important role in soil processes such as mineral weathering, nutrient mobilization and Al detoxification. In this research, a batch experiment...Low-molecular-weight (LMW) organic acids exist widely in soils and play an important role in soil processes such as mineral weathering, nutrient mobilization and Al detoxification. In this research, a batch experiment was conducted to examine the effects of LMW organic acids on dissolution of aluminum in two variably charged soils, an Ultisol and an Oxisol. The results showed that the LMW organic acids enhanced the dissolution of Al in the two investigated soils in the following order: citric > oxalic > malonic > malic > tartaric > salicylic > lactic > maleic. This was generally in agreement with the magnitude of the stability constants for the Al-organic complexes. The effects of LMW organic acids on Al dissolution were greater in the Ultisol than in the Oxisol as compared to their controls. Also, the accelerating effects of citric and oxalic acids on dissolution of Al increased with an increase in pH, while the effects of lactic and salicylic acids decreased. Additionally, when the organic acid concentration was less than 0.2 mmol L-1, the dissolution of Al changed little with increase in acid concentration. However, when the organic acid concentration was greater than 0.2 mmol L-1, the dissolution of Al increased with increase in acid concentration. In addition to the acid first dissociation constant and stability constant of Al-organic complexes, the promoting effects of LMW organic acids on dissolution of Al were also related to their sorption-desorption equilibrium in the soils.展开更多
Objective To evaluate the efficacy and safety of low molecular weight heparin (LMWH) prophylaxis for venous thromboembolism (VTE) after lumbar decompression surgery. Methods Patients at high or the highest risk of VTE...Objective To evaluate the efficacy and safety of low molecular weight heparin (LMWH) prophylaxis for venous thromboembolism (VTE) after lumbar decompression surgery. Methods Patients at high or the highest risk of VTE who underwent lumbar spine surgery in Peking Union Medical College Hospital from January 2004 to April 2011 were included in the present study. All the patients received a half dose of LMWH 6 hours after surgery followed by a full dose LMWH once per day until discharge. We recorded incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding complications, and medication side effects. Results Seventy-eight consecutive patients were eligible and enrolled in this study. The mean hospital stat was 8.5±4.5 days. No symptomatic DVT, PE, or major bleeding events were observed. One patient developed wound ecchymosis, another developed wound bleeding, four had mild hepatic aminotransferase level elevation, and one developed a suspicious allergic reaction. Conclusion LMWH may be applied as an effective and safe prophylaxis for VTE in high-risk patients undergoing lumbar decompression surgery.展开更多
Heparin has been used as an anticoagulant drug for many years, but it has significant side ef fects. In the search for good substitutes, low molecular weight(MW) polysaccharides from S argassum fusiforme have been exa...Heparin has been used as an anticoagulant drug for many years, but it has significant side ef fects. In the search for good substitutes, low molecular weight(MW) polysaccharides from S argassum fusiforme have been examined and confi rmed to possess biological activities. Here, S. fusiforme polysaccharides(SFP) were extracted and subjected to a hydrogen peroxide(H_2O_2) oxidation method for the preparation of low-MW SFP(LSFP). The effects of temperature, pH, and H_2O_2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin(APTT), prothrombin(PT) and thrombin times(TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these ef fects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined ef fects. The details of this mechanism require further verifi cation.展开更多
Gelatin extracted from the body wall of the sea cucumber (Stichopus japonicus) was hydrolyzed with flavourzyme.Low-molecular-weight gelatin hydrolysate (LMW-GH) of 700-1700 Da was produced using an ultrafiltration mem...Gelatin extracted from the body wall of the sea cucumber (Stichopus japonicus) was hydrolyzed with flavourzyme.Low-molecular-weight gelatin hydrolysate (LMW-GH) of 700-1700 Da was produced using an ultrafiltration membrane bioreactor system.Chemiluminescence analysis revealed that LMW-GH scavenges high free radicals in a concentration-dependent manner;IC50 value for superoxide and hydroxyl radicals was 442 and 285 μg mL-1,respectively.LMW-GH exhibited excellent inhibitory characteristics against melanin synthesis and tyrosinase activity in B16 cells.Furthermore,LMW-GH notably increased intracellular glutathione (GSH),which in turn suppressed melanogenesis.LMW-GH performs antioxidation activity,holding the potential of being used as a valuable ingredient in function foods,cosmetics and pharmaceuticals or nutriceuticals.展开更多
A low-molecular-weight polylactide-poly(butylene succinate)(PLA-PBS)copolymer was synthesized and incorporated into polylactide(PLA)as a novel toughening agent by solvent casting.The copolymer had the same chemical ...A low-molecular-weight polylactide-poly(butylene succinate)(PLA-PBS)copolymer was synthesized and incorporated into polylactide(PLA)as a novel toughening agent by solvent casting.The copolymer had the same chemical structure and function as PLA and it was used as a plasticizer to PLA.The copolymer was blended with PLA at a weight ratio from 2 to 10 wt%.Phase separation between PLA and PLA-PBS was not observed from their scanning electron microscopy(SEM)images and the crystal structure of PLA almost remained unchanged based on the X-ray diffraction(XRD)measurement.The melt flow index(MFI)of the blends was higher as the amount of PLA-PBS increased,indicating that the block copolymer did improve the mobility of the PLA chains.Moreover,tensile tests revealed that PLA with greater PLA-PBS copolymer exhibited higher elongation at break and it reached the maximum at 8 wt%of PLA-PBS in PLA,which was around 6 times higher than that of pure PLA.Furthermore,the glass transition temperature,measured by differential scanning calorimetry(DSC),markedly decreased with an increasing amount of the copolymer as it decreased from 61.2℃ for pure PLA to 41.3℃when it was blended with 10 wt%PLA-PBS copolymer.Therefore,the PLA-PBS copolymer was shown to be a promising plasticizer for fully biobased and toughened PLA.展开更多
The composition and vertical profiles of low molecular-weight organic acids (LMWOAs) and the contribution of them to dissolved organic matter (DOM) in sediment porewaters in Bosten Lake, Xinjiang, China were investiga...The composition and vertical profiles of low molecular-weight organic acids (LMWOAs) and the contribution of them to dissolved organic matter (DOM) in sediment porewaters in Bosten Lake, Xinjiang, China were investigated. The results showed that total concentration of LMWOAs was up to 94.5 μmol/L and their proportion in DOM was 5.6%, suggesting that LMWOAs were important chemical components in DOM in lake sediment porewaters. Among the seven LMWOAs, pyruvic and acetic acid had the highest concentrations with 26.30 and 8.31 μmol/L, accounting for 51.4% and 14.92% of LMWOAs, respectively. Trifluoroacetic and sorbic acid had the lowest concentrations, indicating that the compositions of LMWOAs in relative reducing environments were largely different from those reported in glacier, atmosphere and soils. The concentrations of lactic, acetic, formic, sorbic and oxalic acid decreased with increasing depth, probably relating to stronger microbial activities in the initial stage of early diagenesis. Trifluoroacetic acid was mainly anthropogenic with its concentration, showing a diusive trend from the surface to bottom sediments. The concentrations of lactic acid and nitrate generally showed a consistent profile. The increasing concentration of pyruvic acid in the vertical profile was just opposite to that of sulfate, revealing a significant negative relationship between them. Oxalic acid remained constant except for an obvious peak at 6 cm depth. The results indicated the diversities in sources and behaviors for various LMWOAs during early diagenesis in sediments.展开更多
Most research in the past using genetically modified crops (GM crops) has focused on the ecological safety of foreign gene (i.e., the gene flow), gene products (for example, Bt (Bacillus thuringiensis) protein), and t...Most research in the past using genetically modified crops (GM crops) has focused on the ecological safety of foreign gene (i.e., the gene flow), gene products (for example, Bt (Bacillus thuringiensis) protein), and the safety of transgenic food for humans. In this study, changes in both the species and amounts of low-molecular-weight components in cotton (Gossypium hirsutum L.) root exudates after foreign Bt gene overexpression were investigated under different nutritional conditions. Transgenic cotton containing Bt (Bt-cotton), supplemented with all the mineral nutrients, secreted more organic acids than the wild-type cotton (WT). When nitrogen was removed from the full-nutrient solution, the amount of organic acids secretion of Bt-cotton was lesser than that of WT. The roots of the transgenic cotton secreted lesser amounts of amino acids and soluble sugars than the WT roots in the full-nutrient solution. Deficiencies of P and K caused a large increase in the total amino acid and soluble sugar secretions of both Bt-cotton and WT, with larger increases observed in Bt-cotton. Because transferring the foreign Bt gene into cotton can result in alterations in the components of the root exudates, with the effect varying depending on the nutritional status, the cultivation of genetically modified crops, such as Bt-cotton, in soil environments should be more carefully assessed, and the possible effects as a result of the alterations in the root exudate components should be considered.展开更多
Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) ...Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) is clinically as efficient and safe as unfractionated heparin (UH) in patients with diagnosis of acute non-massive PTE, our study compares the efficacy, adverse effects and costs of LMWH and UH. Methods: One hundred and fourteen patients with non-massive acute PTE were randomly divided into LMWH (nadroparin calcium) and UH groups. Oxygenation index, D-dimer, fibrinogen (FG), lung ventilation/perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA) were observed before anticoagula-tion and on day 14 after anticoagulation. Results: In both groups, the ABG (arterial blood gas) analysis showed PaO2 and PaCO2 were elevated, P(A-a)O2 was decreased and oxygenation index (PaO2/FIO2) was elevated, D-dimer and fibrinogen were decreased, lung V/Q and CTPA showed embolized segments reduced (P<0.05). Hemorrhage and thrombocytopenia occurred in 3.5% of the LMWH group. Hemorrhage occurred in 5.3% and thrombocytopenia occurred in 7.0% of the UH group. The average cost in the LMWH group was RMB 1218.60 Yuan and RMB 1541.40 Yuan in the UH group. Conclusion: LMWH and UH are equally effective for treatment of non-massive acute PTE, but LMWH may have a lower prevalence of complications and is less expen-sive.展开更多
Low molecular weight peptide (LMWP) was prepared from clam Paphia undulate and its antiaging effect on D-galactose-induced acute aging in rats, aged Kunming mice, ultraviolet-exposed rats, and thermally injured rats w...Low molecular weight peptide (LMWP) was prepared from clam Paphia undulate and its antiaging effect on D-galactose-induced acute aging in rats, aged Kunming mice, ultraviolet-exposed rats, and thermally injured rats was investigated. P. undulate flesh was homogenized and digested using papain under optimal conditions, then subjected to Sephadex G-25 chromatography to isolate the LMWP. Administration of LMWP significantly reversed D-galactose-induced oxidative stress by increasing the activities of glutathione peroxidase (GPx) and catalase (CAT), and by decreasing the level of malondialdehyde (MDA). This process was accompanied by increased collagen synthesis. The LMWP prevented photoaging and promoted dermis recovery and remission of elastic fiber hyperplasia. Furthermore, treatment with the LMWP helped to regenerate elastic fibers and the collagen network, increased superoxide dismutase (SOD) in the serum and significantly decreased MDA. Thermal scald-induced inflammation and edema were also relieved by the LWMP, while wound healing in skin was promoted. These results suggest that the LMWP from P. undulate could serve as a new antiaging substance in cosmetics.展开更多
Nickel-based catalyst [N,N]NiBr2, in which [N,N] stands for N-(2,6-diisopropylphenyl)pyridine-2-carboxaldimine, shows high activity for ethylene polymerization in the presence of organoaluminum compounds under high et...Nickel-based catalyst [N,N]NiBr2, in which [N,N] stands for N-(2,6-diisopropylphenyl)pyridine-2-carboxaldimine, shows high activity for ethylene polymerization in the presence of organoaluminum compounds under high ethylene pressure to yield polyethylene characteristic of low molecular weight and highly branched chains. Toluene as the solvent is more in favor of catalyst activity, higher molecular weight and branched chains in polyethylene structure as compared to hexane solvent.展开更多
BACKGROUND:Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE:To investigate the effect of low molecular weight heparin-superoxi...BACKGROUND:Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE:To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6(IL-6) overexpressing mice following local cerebral ischemia. DESIGN,TIME AND SETTING:Randomized,cytological,controlled,animal study was performed in the Department of Physiology and Neuroscience,Neurology and Biochemistry and Molecular Biology,Medical University of South Carolina from January 2005 to March 2005. MATERIALS:Nine IL-6 transgenic mice,irrespective of gender,were randomly divided into three groups:sham-operated,model,and treatment,with three mice in each group.With exception of the sham-operated group,right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein,an astrocyte marker,was determined by immunohistochemistry.Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute,Shandong University. METHODS:Two minutes prior to ischemia induction,0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group,respectively.The sham-operated group underwent the same protocols,with the exception of occlusion and treatment. MAIN OUTCOME MEASURES:The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy(x200). RESULTS:In the sham-operated group,there were a large number of astrocytes in the IL-6 transgenic mice.However,the cell bodies were small,and the branches were few and thin.The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups,the number of astrocytes significantly increased,and the cell body became larger,following treatment with low molecular weight heparin-superoxide dismutase conjugate.Astrocytes exhibited hypertrophy and hyperplasia,and the processes became longer and thicker. CONCLUSION:The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.展开更多
AIM:To investigate the antiangiogenic effects and safety of topically administered low-molecular-weight heparintaurocholate 7(LHT7) on corneal neovascularization(CoNV).METHODS:Twenty-four Sprague-Dawley rats were rand...AIM:To investigate the antiangiogenic effects and safety of topically administered low-molecular-weight heparintaurocholate 7(LHT7) on corneal neovascularization(CoNV).METHODS:Twenty-four Sprague-Dawley rats were randomly distributed into four groups of six rats each.The central corneas were cauterized using a silver/potassium nitrate solution.From 2d after cauterization,12.5 mg/mL(low LHT7 group) or 25 mg/mL(high LHT7group) LHT7 was topically administered three times daily;12.5 mg/mL bevacizumab was topically administered as positive control(bevacizumab) group,with normal saline(NS) administered as negative control(NS group).The corneas were digitally photographed to calculate the CoNV percentage from the neovascularized corneal area at 1 and 2wk.RESULTS:The 4 study groups did not have different CoNV percentages at 1wk after injury(P>0.05).However,the low LHT,high LHT,and bevacizumab groups had significantly lower CoNV percentages than the NS group at 2wk(all P<0.05).No significant differences in CoNV percentage were found among the low LHT,high LHT,and bevacizumab groups(all P>0.05).All groups except the NS group had lower CoNV percentages at 2wk postinjury than the levels observed at 1wk(all P<0.05).CONCLUSION:Topically-administered LHT7 inhibited CoNV without complication after chemical cauterization in the rat.展开更多
OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or ...OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or probucol(100mg·kg-1·d-1)were given orally to Goto-Kakizaki type 2 diabetic rats for 12 weeks.Basal blood pressure,acetylcholine-or flow-mediated relaxation of mesenteric and paw arteries,endothelium-dependent dilation of aorta,eNOS phosphorylation and NO production were measured using laser Doppler flowmetry,force myograph,HE staining,Western blot and an NO assay,respectively.The establishment of diabetic cardiomyopathy(DCM)model and were evaluated by echocardiography and isolated heart perfusion.Ventricle staining with HE or Sirius red was performed to investigate the structural changes in myocardium.Oxidative stress and apoptosis were evaluated by enzyme activities,protein expressions and cell stainings in both myocardial tissues and cultured cardiomyocytes.RESULTS In aorta,LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta,as well as mesenteric and paw arteries in diabetic rats.In addition,the reduction in endothelial nitric oxide synthase(eNOS)phosphorylation at Ser1177,eNOS expression and NO production due to diabetes were partially reversed by LMWF treatment.However,probucol,a lipid-modifying drug with antioxidant properties,displayed only mild effects.Moreover,LMWF induced,in a dose-dependent manner,endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta,and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells.On DCM,LMWF has a beneficial effect by enhancing myocardial contractility and mitigating cardiac fibrosis as well as the production of reactive oxygen species(ROS)and myocyte apoptosis in diabetic hearts.CONCLUSION These data demonstrate for the first time that fucoidan protects vasoendothelial and cardiac function against diabetic injury in type 2diabetes rats via,at least in part,preservation of eNOS function,amelioration of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis.Fucoidan is therefore a potential candidate drug for protection of endothelium and heart in diabetic cardiovascular complications.展开更多
基金supported by Korea Institute of Marine Science&Technology Promotion(KIMST)funded by the Ministry of Oceans and Fisheries,Korea(20220488)。
文摘Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunbergii and appraised their LMPST on palmitic acid(PA)induced lipid accretion in Hep G2,and 3T3-L1 cells.LMPST treatment lessened lipid deposition and intracellular free fatty acid and triglyceride intensities in PA-treated above mentioned cells.The mechanistic study publicized that LMPST2 significantly suppressed adipogenesis and stimulated the PA-treated 3T3-L1 cells occupied in the lipolysis pathway.Furthermore,in PA-treated Hep G2 cells,the free fatty acid oxidation was significantly increased by LMPST2.Given these constructive properties of LMPST2 from S.thunbergii,is a potential candidate for diminishing the intracellular lipids,and for a therapeutic agent in those conditions.
基金Supported by the National Natural Science Foundation of China (Nos.42176137,81872906)the Nantong Science and Technology Project (No.MS12021037)+2 种基金the STS Program of Chinese Academy of Sciences (No.KFJ-STS-QYZD-195)the K.C.Wong Education FoundationCAS。
文摘The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate kidney dysfunction in chronic kidney diseases and inhibit diabetic vascular complications.In many studies,LMWF was found to be more potent than fucoidan with high molecular weight.However,the pharmacokinetics of LMWF still remains unclear.The purpose of the research is to compare the pharmacokinetics of fucoidan with high molecular weight(136 kDa)with that low molecular weight(9.5 kDa)after oral administration to ICR mice.Since fucose is the main and representative monosaccharide of fucoidans,we evaluate the pharmacokinetics of fucoidan and LMWF by determining the fucose concentration in mice serum.Both fucoidan and LMWF were absorbed following oral administration.Fucoidan and LMWF were provided to mice by oral administration with 60 mg/kg and the maximum Concentration(C_(max))was found at 2.5 h(0.66±0.32 mg/L)for Fucoidan and 1.5 h(1.01±0.56 mg/L)for LMWF,respectively.It seems that LMWF had a higher area under the curve(AUC_(0–t))and was absorbed more quickly than fucoidan.The estimated bioavailability of LMWF was28.3%in the mice treated with a single dose of 30 mg/kg.In addition,LMWF was found widely spreaded into different tissues following oral administration and the highest concentration was found in kidney at 19.93±7.02μg/g.In this study,we first studied the pharmacokinetics of LMWF,in order to help to understand the function of LMWF.And our results shed light on the potential of development of drugs based on LMWF.
基金financially supported by the State Key Research and Development Plan(2019YFC1605002)。
文摘As one of the most important cereals,wheat(Triticum aestivum)has high nutritional value and is widely cultivated in China.However,wheat can cause severe allergic reactions,and a growing number of people are developing allergies to Chinese wheat.Low molecular weight glutenin(LMW-GS),an important allergen in susceptible populations,is responsible for celiac disease and wheat contacts dermatitis.In this study,LMW-GS was highly purified from Chinese wheat(Xiaoyan 6)and further identified and characterized.In addition,8 peptides were predicted efficiently by 5 immunological tools,among which 5 peptides showed significant immunoglobulin E binding abilities.Two specific epitopes were found to be in the non-conserved region of the amino acid sequence of LMW-GS,which was speculated to be the specific epitope of Chinese wheat.This systematic research of LMW-GS may provide new insights into the prevention of wheat allergy and development of hypoallergenic wheat products.
基金The University of Arizona Hematology and Medical Oncology Fellowship program
文摘BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulation treatment have an associated increase rate.GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants(DOAC),especially with active cancer therapies.AIM To evaluate patient risk factors,effectiveness(VTE)and safety(MB)of DOACs and low molecular weight heparin(LMWH)in patients with active GICA-VTE.METHODS A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed.Inclusion criteria included active GI cancer diagnosed at any stage or treatment+/-6 mo of VTE diagnosis,whom were prescribed 6 mo or more of DOACs or LMWH.The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events.Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTS A total of 144 patients were prescribed anticoagulation,in which 106 fulfilled inclusion criteria apixaban(27.3%),rivaroxaban(34.9%)and enoxaparin(37.7%),and 38 were excluded.Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event,with 62%males,80%Caucasian,70%stage IV,pancreatic cancer(40.5%),30%Khorana Score(≥3 points),and 43.5%on active chemotherapy.Sixty-four percent of patients completed anticoagulation therapy(range 1 to 43 mo).Recurrent VTE at 6 mo was noted in 7.5%(n=3),6.8%(n=2)and 2.7%(n=1)of patients on enoxaparin,apixaban and rivaroxaban,respectively(all P=NS).MB at 6 mo were 5%(n=2)for enoxaparin,6.8%(n=2)for apixaban and 21.6%(n=8)for rivaroxaban(overall P=0.048;vs LMWH P=0.0423;all other P=NS).Significant predictors of a primary or secondary outcome for all anticoagulation therapies included:Active systemic treatment(OR=5.1,95%CI:1.3-19.3),high Khorana Score[≥3 points](OR=5.5,95%CI:1.7-17.1),active smoker(OR=6.7,95%CI:2.1-21.0),pancreatic cancer(OR=6.8,95%CI:1.9-23.2),and stage IV disease(OR=9.9,95%CI:1.2-79.1).CONCLUSION Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.
文摘Incubation experiments were conducted to investigate the dynamics of low- molecufar-weight aliphatic acids in two andosols with and without plant materials. Results showed that amount of low- molecular-weight aliphatic acids in soils alone varied considerably with water regime under which the soil was incubated,duration of incubation and soil organic matter content, ranging from 257-860 pmol kg-1 soil I of which 19%～33% was in free state. Incorporation of plant materials increased greatly both the amount and number of members of low- molecular- weight aliphaticacidst and also the proporticn of low-molec "far-weight aliphatic acids occurred in free state. Generally, among these aliphatic acids detected, acetic, propionic, glyoxalic and formic acids were predominant.
基金Project supported by the National Natural Science Foundation of China (No. 40271062).
文摘Low-molecular-weight (LMW) organic acids exist widely in soils and play an important role in soil processes such as mineral weathering, nutrient mobilization and Al detoxification. In this research, a batch experiment was conducted to examine the effects of LMW organic acids on dissolution of aluminum in two variably charged soils, an Ultisol and an Oxisol. The results showed that the LMW organic acids enhanced the dissolution of Al in the two investigated soils in the following order: citric > oxalic > malonic > malic > tartaric > salicylic > lactic > maleic. This was generally in agreement with the magnitude of the stability constants for the Al-organic complexes. The effects of LMW organic acids on Al dissolution were greater in the Ultisol than in the Oxisol as compared to their controls. Also, the accelerating effects of citric and oxalic acids on dissolution of Al increased with an increase in pH, while the effects of lactic and salicylic acids decreased. Additionally, when the organic acid concentration was less than 0.2 mmol L-1, the dissolution of Al changed little with increase in acid concentration. However, when the organic acid concentration was greater than 0.2 mmol L-1, the dissolution of Al increased with increase in acid concentration. In addition to the acid first dissociation constant and stability constant of Al-organic complexes, the promoting effects of LMW organic acids on dissolution of Al were also related to their sorption-desorption equilibrium in the soils.
文摘Objective To evaluate the efficacy and safety of low molecular weight heparin (LMWH) prophylaxis for venous thromboembolism (VTE) after lumbar decompression surgery. Methods Patients at high or the highest risk of VTE who underwent lumbar spine surgery in Peking Union Medical College Hospital from January 2004 to April 2011 were included in the present study. All the patients received a half dose of LMWH 6 hours after surgery followed by a full dose LMWH once per day until discharge. We recorded incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding complications, and medication side effects. Results Seventy-eight consecutive patients were eligible and enrolled in this study. The mean hospital stat was 8.5±4.5 days. No symptomatic DVT, PE, or major bleeding events were observed. One patient developed wound ecchymosis, another developed wound bleeding, four had mild hepatic aminotransferase level elevation, and one developed a suspicious allergic reaction. Conclusion LMWH may be applied as an effective and safe prophylaxis for VTE in high-risk patients undergoing lumbar decompression surgery.
基金Supported by the Ocean Public Welfare Scientifi c Research Project,State Oceanic Administration of the People’s Republic of China(No.201505033)the Qingdao People’s Livelihood Science and Technology Program(No.16-6-2-41-nsh)
文摘Heparin has been used as an anticoagulant drug for many years, but it has significant side ef fects. In the search for good substitutes, low molecular weight(MW) polysaccharides from S argassum fusiforme have been examined and confi rmed to possess biological activities. Here, S. fusiforme polysaccharides(SFP) were extracted and subjected to a hydrogen peroxide(H_2O_2) oxidation method for the preparation of low-MW SFP(LSFP). The effects of temperature, pH, and H_2O_2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin(APTT), prothrombin(PT) and thrombin times(TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these ef fects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined ef fects. The details of this mechanism require further verifi cation.
基金supported by the National High-Tech Research and Development Project of China (No.2007AA091805)National Natural Science Foundation of China (Nos.30871944 and 30972284)National Key Technology Research and Development Program of China (No.2008BAD94B05)
文摘Gelatin extracted from the body wall of the sea cucumber (Stichopus japonicus) was hydrolyzed with flavourzyme.Low-molecular-weight gelatin hydrolysate (LMW-GH) of 700-1700 Da was produced using an ultrafiltration membrane bioreactor system.Chemiluminescence analysis revealed that LMW-GH scavenges high free radicals in a concentration-dependent manner;IC50 value for superoxide and hydroxyl radicals was 442 and 285 μg mL-1,respectively.LMW-GH exhibited excellent inhibitory characteristics against melanin synthesis and tyrosinase activity in B16 cells.Furthermore,LMW-GH notably increased intracellular glutathione (GSH),which in turn suppressed melanogenesis.LMW-GH performs antioxidation activity,holding the potential of being used as a valuable ingredient in function foods,cosmetics and pharmaceuticals or nutriceuticals.
文摘A low-molecular-weight polylactide-poly(butylene succinate)(PLA-PBS)copolymer was synthesized and incorporated into polylactide(PLA)as a novel toughening agent by solvent casting.The copolymer had the same chemical structure and function as PLA and it was used as a plasticizer to PLA.The copolymer was blended with PLA at a weight ratio from 2 to 10 wt%.Phase separation between PLA and PLA-PBS was not observed from their scanning electron microscopy(SEM)images and the crystal structure of PLA almost remained unchanged based on the X-ray diffraction(XRD)measurement.The melt flow index(MFI)of the blends was higher as the amount of PLA-PBS increased,indicating that the block copolymer did improve the mobility of the PLA chains.Moreover,tensile tests revealed that PLA with greater PLA-PBS copolymer exhibited higher elongation at break and it reached the maximum at 8 wt%of PLA-PBS in PLA,which was around 6 times higher than that of pure PLA.Furthermore,the glass transition temperature,measured by differential scanning calorimetry(DSC),markedly decreased with an increasing amount of the copolymer as it decreased from 61.2℃ for pure PLA to 41.3℃when it was blended with 10 wt%PLA-PBS copolymer.Therefore,the PLA-PBS copolymer was shown to be a promising plasticizer for fully biobased and toughened PLA.
基金supported by the National Basic Research Program (973) of China (No. 2008CB418200)the National Natural Science Foundation of China (No.U0833603, 40632011, 40873080)
文摘The composition and vertical profiles of low molecular-weight organic acids (LMWOAs) and the contribution of them to dissolved organic matter (DOM) in sediment porewaters in Bosten Lake, Xinjiang, China were investigated. The results showed that total concentration of LMWOAs was up to 94.5 μmol/L and their proportion in DOM was 5.6%, suggesting that LMWOAs were important chemical components in DOM in lake sediment porewaters. Among the seven LMWOAs, pyruvic and acetic acid had the highest concentrations with 26.30 and 8.31 μmol/L, accounting for 51.4% and 14.92% of LMWOAs, respectively. Trifluoroacetic and sorbic acid had the lowest concentrations, indicating that the compositions of LMWOAs in relative reducing environments were largely different from those reported in glacier, atmosphere and soils. The concentrations of lactic, acetic, formic, sorbic and oxalic acid decreased with increasing depth, probably relating to stronger microbial activities in the initial stage of early diagenesis. Trifluoroacetic acid was mainly anthropogenic with its concentration, showing a diusive trend from the surface to bottom sediments. The concentrations of lactic acid and nitrate generally showed a consistent profile. The increasing concentration of pyruvic acid in the vertical profile was just opposite to that of sulfate, revealing a significant negative relationship between them. Oxalic acid remained constant except for an obvious peak at 6 cm depth. The results indicated the diversities in sources and behaviors for various LMWOAs during early diagenesis in sediments.
基金Project supported by the Knowledge Innovation Program of the Institute of Soil Science, Chinese Academy of Sciences,and the National Natural Science Foundation of China (No. 30270789).
文摘Most research in the past using genetically modified crops (GM crops) has focused on the ecological safety of foreign gene (i.e., the gene flow), gene products (for example, Bt (Bacillus thuringiensis) protein), and the safety of transgenic food for humans. In this study, changes in both the species and amounts of low-molecular-weight components in cotton (Gossypium hirsutum L.) root exudates after foreign Bt gene overexpression were investigated under different nutritional conditions. Transgenic cotton containing Bt (Bt-cotton), supplemented with all the mineral nutrients, secreted more organic acids than the wild-type cotton (WT). When nitrogen was removed from the full-nutrient solution, the amount of organic acids secretion of Bt-cotton was lesser than that of WT. The roots of the transgenic cotton secreted lesser amounts of amino acids and soluble sugars than the WT roots in the full-nutrient solution. Deficiencies of P and K caused a large increase in the total amino acid and soluble sugar secretions of both Bt-cotton and WT, with larger increases observed in Bt-cotton. Because transferring the foreign Bt gene into cotton can result in alterations in the components of the root exudates, with the effect varying depending on the nutritional status, the cultivation of genetically modified crops, such as Bt-cotton, in soil environments should be more carefully assessed, and the possible effects as a result of the alterations in the root exudate components should be considered.
文摘Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) is clinically as efficient and safe as unfractionated heparin (UH) in patients with diagnosis of acute non-massive PTE, our study compares the efficacy, adverse effects and costs of LMWH and UH. Methods: One hundred and fourteen patients with non-massive acute PTE were randomly divided into LMWH (nadroparin calcium) and UH groups. Oxygenation index, D-dimer, fibrinogen (FG), lung ventilation/perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA) were observed before anticoagula-tion and on day 14 after anticoagulation. Results: In both groups, the ABG (arterial blood gas) analysis showed PaO2 and PaCO2 were elevated, P(A-a)O2 was decreased and oxygenation index (PaO2/FIO2) was elevated, D-dimer and fibrinogen were decreased, lung V/Q and CTPA showed embolized segments reduced (P<0.05). Hemorrhage and thrombocytopenia occurred in 3.5% of the LMWH group. Hemorrhage occurred in 5.3% and thrombocytopenia occurred in 7.0% of the UH group. The average cost in the LMWH group was RMB 1218.60 Yuan and RMB 1541.40 Yuan in the UH group. Conclusion: LMWH and UH are equally effective for treatment of non-massive acute PTE, but LMWH may have a lower prevalence of complications and is less expen-sive.
基金Supported by the Knowledge Innovation Program of Chinese Academy of Sciences(No.KZCX2-EW-Q214)the Comprehensive Strategic Cooperation Programs between Guangdong Province and Chinese Academy of Sciences(Nos.2011A090100008,2009B091300018,2010B090300027)the Marine Fisheries Technology Promotion Special Program of Guangdong Province,China(No.A2009009-035(a))
文摘Low molecular weight peptide (LMWP) was prepared from clam Paphia undulate and its antiaging effect on D-galactose-induced acute aging in rats, aged Kunming mice, ultraviolet-exposed rats, and thermally injured rats was investigated. P. undulate flesh was homogenized and digested using papain under optimal conditions, then subjected to Sephadex G-25 chromatography to isolate the LMWP. Administration of LMWP significantly reversed D-galactose-induced oxidative stress by increasing the activities of glutathione peroxidase (GPx) and catalase (CAT), and by decreasing the level of malondialdehyde (MDA). This process was accompanied by increased collagen synthesis. The LMWP prevented photoaging and promoted dermis recovery and remission of elastic fiber hyperplasia. Furthermore, treatment with the LMWP helped to regenerate elastic fibers and the collagen network, increased superoxide dismutase (SOD) in the serum and significantly decreased MDA. Thermal scald-induced inflammation and edema were also relieved by the LWMP, while wound healing in skin was promoted. These results suggest that the LMWP from P. undulate could serve as a new antiaging substance in cosmetics.
文摘Nickel-based catalyst [N,N]NiBr2, in which [N,N] stands for N-(2,6-diisopropylphenyl)pyridine-2-carboxaldimine, shows high activity for ethylene polymerization in the presence of organoaluminum compounds under high ethylene pressure to yield polyethylene characteristic of low molecular weight and highly branched chains. Toluene as the solvent is more in favor of catalyst activity, higher molecular weight and branched chains in polyethylene structure as compared to hexane solvent.
文摘BACKGROUND:Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE:To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6(IL-6) overexpressing mice following local cerebral ischemia. DESIGN,TIME AND SETTING:Randomized,cytological,controlled,animal study was performed in the Department of Physiology and Neuroscience,Neurology and Biochemistry and Molecular Biology,Medical University of South Carolina from January 2005 to March 2005. MATERIALS:Nine IL-6 transgenic mice,irrespective of gender,were randomly divided into three groups:sham-operated,model,and treatment,with three mice in each group.With exception of the sham-operated group,right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein,an astrocyte marker,was determined by immunohistochemistry.Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute,Shandong University. METHODS:Two minutes prior to ischemia induction,0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group,respectively.The sham-operated group underwent the same protocols,with the exception of occlusion and treatment. MAIN OUTCOME MEASURES:The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy(x200). RESULTS:In the sham-operated group,there were a large number of astrocytes in the IL-6 transgenic mice.However,the cell bodies were small,and the branches were few and thin.The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups,the number of astrocytes significantly increased,and the cell body became larger,following treatment with low molecular weight heparin-superoxide dismutase conjugate.Astrocytes exhibited hypertrophy and hyperplasia,and the processes became longer and thicker. CONCLUSION:The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.
基金Supported by the Student Research Grant of University of Ulsan College of Medicine,Seoul,Korea(No.12-13)the Asan Institute for Life Sciences,Seoul,Korea(No.2014-464)
文摘AIM:To investigate the antiangiogenic effects and safety of topically administered low-molecular-weight heparintaurocholate 7(LHT7) on corneal neovascularization(CoNV).METHODS:Twenty-four Sprague-Dawley rats were randomly distributed into four groups of six rats each.The central corneas were cauterized using a silver/potassium nitrate solution.From 2d after cauterization,12.5 mg/mL(low LHT7 group) or 25 mg/mL(high LHT7group) LHT7 was topically administered three times daily;12.5 mg/mL bevacizumab was topically administered as positive control(bevacizumab) group,with normal saline(NS) administered as negative control(NS group).The corneas were digitally photographed to calculate the CoNV percentage from the neovascularized corneal area at 1 and 2wk.RESULTS:The 4 study groups did not have different CoNV percentages at 1wk after injury(P>0.05).However,the low LHT,high LHT,and bevacizumab groups had significantly lower CoNV percentages than the NS group at 2wk(all P<0.05).No significant differences in CoNV percentage were found among the low LHT,high LHT,and bevacizumab groups(all P>0.05).All groups except the NS group had lower CoNV percentages at 2wk postinjury than the levels observed at 1wk(all P<0.05).CONCLUSION:Topically-administered LHT7 inhibited CoNV without complication after chemical cauterization in the rat.
基金The project supported by National Natural Science Foundation of China(81370339)Promotion Project of Beijing Education Committee(TJSHJ201510025005)
文摘OBJECTIVE To investigate the protective effect against diabetes cardiovascular complications of low molecular weight fucoidan(LMWF)from L.japonica in Qindao, China. METHODS LMWF(50,100 and 200mg·kg-1·d-1)or probucol(100mg·kg-1·d-1)were given orally to Goto-Kakizaki type 2 diabetic rats for 12 weeks.Basal blood pressure,acetylcholine-or flow-mediated relaxation of mesenteric and paw arteries,endothelium-dependent dilation of aorta,eNOS phosphorylation and NO production were measured using laser Doppler flowmetry,force myograph,HE staining,Western blot and an NO assay,respectively.The establishment of diabetic cardiomyopathy(DCM)model and were evaluated by echocardiography and isolated heart perfusion.Ventricle staining with HE or Sirius red was performed to investigate the structural changes in myocardium.Oxidative stress and apoptosis were evaluated by enzyme activities,protein expressions and cell stainings in both myocardial tissues and cultured cardiomyocytes.RESULTS In aorta,LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta,as well as mesenteric and paw arteries in diabetic rats.In addition,the reduction in endothelial nitric oxide synthase(eNOS)phosphorylation at Ser1177,eNOS expression and NO production due to diabetes were partially reversed by LMWF treatment.However,probucol,a lipid-modifying drug with antioxidant properties,displayed only mild effects.Moreover,LMWF induced,in a dose-dependent manner,endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta,and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells.On DCM,LMWF has a beneficial effect by enhancing myocardial contractility and mitigating cardiac fibrosis as well as the production of reactive oxygen species(ROS)and myocyte apoptosis in diabetic hearts.CONCLUSION These data demonstrate for the first time that fucoidan protects vasoendothelial and cardiac function against diabetic injury in type 2diabetes rats via,at least in part,preservation of eNOS function,amelioration of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis.Fucoidan is therefore a potential candidate drug for protection of endothelium and heart in diabetic cardiovascular complications.
