Evaluation of the intracellular lipid-lowering effect of polyphenols extract from highland barley in HepG2 cells

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.

Lipids,lipid-lowering drug and sepsis:a Mendelian randomization study

lipid-lowering interventions on the disease.Methods:Two-sample Mendelian randomization analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,triglycerides,apolipoprotein B and apolipoprotein A-I levels with risks for sepsis,and those of low-density lipoprotein cholesterol(HMGCR,PCSK9,NPC1L1),triglycerides(LPL,ANGPTL3,APOC3)and high-density lipoprotein cholesterol(CETP),apolipoprotein A-I(CETP),apolipoprotein B(HMGCR,PCSK9,NPC1L1,LPL,APOC3)with sepsis.Results:HMGCR-mediated low-density lipoprotein cholesterol and apolipoprotein B were associated with an increased risk of sepsis,with an odds ratio value of 1.4(95%confidence interval(CI):1.06-1.84,P=0.017)and 1.41(95%CI:1.01-1.98,P=0.046).CETP-mediated high-density lipoprotein cholesterol and apolipoprotein A-I were associated with a reduced risk of sepsis,with an odds ratio of 0.87(95%CI:0.82-0.92,P<0.01)respectively and 0.84(95%CI:0.78-0.9,P<0.01).Sensitivity analysis showed that the results were robust.Conclusion:HMG-CoA reductase inhibitors and CETP inhibitors may contribute to the prevention and treatment of sepsis.

Role of lipid-lowering agents in the management of diabetic retinopathy

Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus(DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM(T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy.

Lipid-lowering effect of Oroxylum indicum(L.)Kurz extract in hyperlipidemic mice

Objective:To investigate the effect of Oroxylum indicum fruit extract on high-fat diet-induced hyperlipidemic mice.Methods:The phytochemical composition of Oroxylum indicum fruit extract was determined by liquid chromatographymass spectrometry/mass spectrometry(LC-MS/MS)and gas chromatography-mass spectrometry.Forty-two male mice were used.The mice were divided into six groups:normal control,high-fat diet control,simvastatin treatment(20 mg/kg BW/day),and Oroxylum indicum fruit extract(100,200,300 mg/kg BW/day)treatment groups.Food intake,body weight,serum parameters,lipid profile,and histopathological lesions of the kidney,liver,and epididymal fat were observed.Results:LC-MS/MS results revealed four major components of Oroxylum indicum fruit extract:luteolin,apigenin,baicalein,and oroxylin A.Twenty-seven volatile oils were identified from Oroxylum indicum fruit extract.Daily oral administration of Oroxylum indicum fruit extract at 100 to 300 mg/kg BW/day significantly reduced the body weight,total cholesterol,triglyceride,and low-density lipoprotein cholesterol level(P<0.05),whereas high-density lipoprotein cholesterol was higher than the high-fat diet control group.Treatment with 300 mg/kg BW/day Oroxylum indicum fruit extract reduced the pathological lesion and prevented fat accumulation in the kidney and liver.Conclusions:Oroxylum indicum fruit extract has hypolipidemic effect in hyperlipidemic mice,and the active ingredients of Oroxylum indicum fruit extract,both flavonoids and volatile oils,should be further explored as an antihyperlipidemic agent.

Effects of lipid-lowering agents on diabetic retinopathy: a Meta-analysis and systematic review

AIM：To clarify this controversy and to provide evidence for application of lipid lowering agents in treatment of diabetic retinopathy（DR）.METHODS：We searched the databases of Pub Med,Embase and Cochrane Library Central Register of Controlled Trials（CENTRAL）and abstracts from main annual meetings up to January 1,2017.Google scholar and Clinical Trials.gov were also searched for unpublished relevant studies.We included randomized controlled trials（RCTs）that studied lipid-lowering agents in type 1 or type 2 diabetes in this Meta-analysis.The primary endpoint was the progression of DR,and the secondary endpoints included vision loss,development of diabetic macular edema（DME）and aggravation of hard exudates.The pooled odds ratios（OR）with corresponding 95%confidence intervals（95%CIs）were calculated.RESULTS：After systemic and manual literature search by two independent investigators,we included 8 RCTs from 7 published articles with 13 454 participants in this Meta-analysis.The results revealed that lipid-lowering drugs were associated with reduced risk in DR progression[OR=0.77（95%CI：0.62,0.96）,P=0.02].Lipid-lowering agents might have protective effect on DME compared to placebo,although the difference was not statistically significant[OR=0.60（95%CI：0.34,1.08）,P=0.09].However,no significant differences in the worsening of vision acuity[OR=0.96（95%CI：0.81,1.14）,P=0.64]and hard exudates[OR=0.50（95%CI：0.15,1.74）,P=0.28]were found between the lipidlowering drugs and the placebo groups.CONCLUSION：In DR patients,lipid-lowering agents show a protective effect on DR progression and might be associated with reduced risk in the development of DME.However,lipid-lowering agents have no effects on vision loss and hard exudates aggravation.Further clinical trials in larger scale are required to confirm the conclusion of this study and thus justify the use of intensive control lipids with anti-lipid agents at the early stages of DR.

Characteristic chemical profile of Juhe Fang extract with lipid-lowering properties

Objective:The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract(JHFE)and to determine its characteristic chemical profile in vitro and in vivo.Methods:A hyperlipidemia model was established by feeding mice a high-fat diet(HFD).After treatment for 30 days,serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were measured with an automatic biochemistry analyzer.The components from JHFE obtained from in vivo and in vitro experiments were investigated using an UPLC-Q Exactive-Orbitrap MS/MS.Results:The TC,TG,and LDL-C in the serum significantly decreased and the HDL-C significantly increased after JHFE treatment.A total of 95 compounds from JHEF including 15 phenolic acids(PA),4 phenylethanoid glycosides(PG),24 flavonoids(F),14 triterpenoids(T),10 diterpenoid glycosides(D),18 alkaloids(A)and 10 others(O)were identified.Trigonelline was discovered for the first time in a herbal medicine of Juhe Fang.Furthermore,68 compounds were identified in vivo including 28 prototype compounds and 40 metabolites.The metabolic characteristics of these components were revealed including identification of new metabolites of 4-hydroxyphenyl ethyl-8-O-[a-L-arabinopyranosyl-(1/6)]-b-D-glucopyranoside(PEG)and lirinidine.A total of 43 components from JHFE were absorbed and/or metabolized.The contribution rate of each type of chemical component from JHFE to its lipidlowering effect from high to low were A,F,PG,PA,D and T.Conclusion:The results of this study showed that JHFE demonstrated a significant lipid-lowering effect in a high-fat diet(HFD)-induced hyperlipidemia mouse model.Specific types of PA,PG,F,D,T and A formed the pharmaceutical architecture of the lipid-lowering effect of JHFE.This study should prove useful for clarifying the components responsible for the lipid-lowering effect of JHFE and provide a basis for precision quality control research.

Intensive lipid-lowering therapy,time to think beyond low-density lipoprotein cholesterol

Statins have been shown to be effective in reducing cardiovascular events.Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical outcomes.Unselective application of these treatments is undesirable and unaffordable and,therefore,has been guided by LDL-c level.Nonetheless,the residual risk in the post-statin era is markedly heterogeneous,including thrombosis and inflammation risks.Moreover,the lipoprotein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a).Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease,post coronary artery bypass graft and diabetes.Notably,these clinical entities share similar phenotype of large burden of atherosclerotic plaques.Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites.Those patients may be suitable candidates for intensive lipid lowering treatment.

(+)/(-)-Mycosphatide A,a pair of highly oxidized polyketides with lipid-lowering activity from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01

(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.

A systematic,updated review of Xuezhikang,a domestically developed lipid-lowering drug,in the application of cardiovascular diseases

Cardiovascular diseases(CVDs)are a major threat to public health globally.A large proportion of people with dyslipidaemia have poorly controlled lipid levels,emphasizing the need for alternative lipid-lowering treatments that are both effective and safe.Xuezhikang,a red yeast rice(RYR)extract,containing 13 kinds of monacolins and other bioactive components,emerges as one such promising option.Its discovery was built on a long history of RYR use as a functional food supplement and traditional Chinese medicine.Several randomized,controlled clinical trials have substantiated its lipid-lowering effects and its potential to protect against CVDs.Safety concerns with statins did not arise during decades of experience with Xuezhikang treatment in clinical practice.The approval of Xuezhikang in multiple regions of Asia marked a conceptual shift in CVD management,moving from single agents to polypills and from synthetic medicines to natural extracts.This review comprehensively addresses important topics related to this medicinal natural extract,including the ancient utilization of RYR,the development of Xuezhikang,its mechanisms of action,pleiotropic effects,clinical studies,challenges,and future perspectives to enhance our understanding regarding the role of Xuezhikang,a representative,domestic lipid-lowering drug of RYR,in prevention and treatment of CVD.

Is medical management useful in Moyamoya disease?

Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral vessels.Addressing antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic complications.Transcranial doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic treatments.Furthermore,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension status.Additionally,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains elusive.Com-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and development.This protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

(+)/(-)-Gerbeloid A,a pair of unprecedented coumarin-based polycyclic meroterpenoid enantiomers from Gerbera piloselloides:Structural elucidation,semi-synthesis,and lipid-lowering activity

A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.2.2.0^(3,8)]decene scaffold.Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis.Guided by the hypothetical biosynthetic pathway,the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6πelectrocyclization and intramolecular[2+2]photocycloaddition.Subsequently,the results of the biological activity assay demonstrated that both(+)-1a and(-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model.Notably,the lipid-lowering activity of(+)-1a is better than that of(-)-1b at the same concentration,and molecular mechanism study has shown that(+)-1a and(-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγsignaling and Perilipin signaling in vitro and in vivo.Our findings provide a promising drug model molecule for the treatment of obesity.

Influences of Lactiplantibacillus plantarum and Saccharomyces cerevisiae fermentation on the nutritional components,flavor property and lipid-lowering effect of highland barley

Highland barley is a well-known cereal in Qinghai-Tibet Plateau area with high nutritional value,which has been reported to be a health-promoting grain for the obesity and the diabetes.Fermentation by certain microbiota can improve the flavor property and nutritional characteristics.In the present study,Lactiplantibacillus plantarum and Saccharomyces cerevisiae were singly or jointly applied to ferment highland barley,and the profile of volatile substances and lipid-lowering effects of the respective extracts were analyzed.Results indicated that either L.plantarum or S.cerevisiae or co-fermentation could consume the polysaccharides of highland barley to provide energy,and dramatically increase the contents of total protein and polyphenol.Gas chromatography-mass spectrometry(GC-MS)analysis revealed that the presence of S.cerevisiae was critical for production of the pleasant flavors,especially for the ethyl ester substances including hexadecanoic acid ethyl,hexanoic acid ethyl ester and so on.Meanwhile,we found that fermented highland barley extracts by L.plantarum exhibited stronger lipid-lowering effects in Caenorhabditis elegans than that by S.cerevisiae,while the co-fermentation not only emitted pleasant odors but also exerted high hypolipidemic function.In all,co-fermentation by L.plantarum and S.cerevisiae was proposed to be a promising processing to improve the flavor and functional properties of highland barley.

Proprotein convertase subtilisin/kexin type 9 inhibitors in peripheral artery disease:A review of efficacy,safety,and outcomes

Peripheral artery disease(PAD)is a common condition characterized by atherosclerosis in the peripheral arteries,associated with concomitant coronary and cerebrovascular diseases.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients.This review focuses on the efficacy,safety,and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed.Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events,offering a potential treatment option for PAD patients.Safety evaluations from trials show few adverse events,most of which are injection-site reactions,indicating the overall safety profile of PCSK9 inhibitors.Clinical outcomes show a reduction in cardiovascular events,ischemic strokes,and major adverse limb events.However,despite these positive findings,PCSK9 inhibitors are still underutilized in clinical practice,possibly due to a lack of awareness among care providers and cost concerns.Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.

Acute liver injury induced by weight-loss herbal supplements

We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients dem onstrated f indings consistent with drug-induced acute liver injury. To our knowledge, we are the fi rst instit ute to report acute liver injury from both of these two typ es of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supp lements for the purpose of weight loss.

Ischemic colitis induced by the newly reformulated multicomponent weight-loss supplement Hydroxycut~

Ischemic colitis accounts for 6%-18% of causes of acute lower gastrointestinal bleeding. It is more often multifactorial and more common in elderly. Drugs are considered important causative agents of this disease with different mechanisms. In this paper, we describe a 37-year-old otherwise healthy female presented with sudden onset diffuse abdominal pain and bloody stool. Radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her only suspected factor was hydroxycut which she had been taking for a period of 1 mo prior to her presentation. Her condition improved uneventfully after cessation of hydroxycut, bowel rest, intravenous hydration, and antibiotics. This is a first case of ischemic colitis with clear relationship with hydroxycut use (Naranjo score of 7). Our case demonstrates the importance of questioning patients regarding the usage of dietary supplements; especially since many patients consider them safe anddo not disclose their use voluntarily to their physicians. Hydroxycut has to be considered as a potential trigger for otherwise unexplained ischemic colitis.

A Weight-Loss and Healthy Living Program for Men Delivered in Swedish Football and Ice-Hockey Clubs(ViSiT):Results from the ViSiT Feasibility Study

Background: Men appear less interested than women in engaging in health-promoting programs. We investigated the feasibility and proof of concept of a novel intervention program targeting male supporters of professional sports clubs. Methods: Our intervention is called ViSiT and the target population in this study was overweight male supporters aged 35 - 65 years with a body mass index ≥ 28 kg/m2, recruited through one football and one ice-hockey club. The participants (n = 22) participated in a 12-week lifestyle intervention with a 52-week follow-up. Body fat was assessed using bioelectrical impedance analysis. Results: The retention rate was high with 21 participants completing the 12-week program and 17 attending at least 10 of 12 sessions. Mean (standard deviation) body weight and fat reduction after 12 weeks was 8.2 (4.6) kg and 6.6 (3.6) kg, respectively. At 52 weeks, body weight and fat reduction were maintained at 6.4 (6.7) kg and 4.5 (6.5) kg. Even after 52 weeks follow-up, the participants appreciated most components of the ViSiT program and perceived the ViSiT program to have high impact on most health-related aspects investigated. Conclusions: The ViSiT program demonstrated a successful retention rate and clinically relevant weight reduction in Swedish overweight men. The maintenance of bodyweight reduction and positive experience after 1 year indicate a long-term effect of the ViSiT concept.

Model for estimating the weight-loss ratio of damaged Korla fragrant pears

To predict the weight-loss ratio of Korla fragrant pears effectively,improve commodity value and study the variation laws of the weight-loss ratio of damaged fragrant pears during storage,this study predicted the weight-loss ratio of fragrant pears by utilizing the generalized regression neural network(GRNN),support vector regression(SVR),partial least squares regression(PLSR)and error back propagation neural network(BPNN).The prediction performances of GRNN,SVR,PLSR and BPNN models were compared comprehensively,and the optimal model was determined.In addition,the optimal prediction model was verified.The results show that weight-loss ratio of fragrant pears increases gradually with the extension of storage time.During storage,the weight-loss ratio of fragrant pears is positively related to the degree of damage.The trained GRNN,SVR,PLSR and BPNN models can be used to predict the weight-loss ratio of fragrant pears.The BPNN model is the most accurate in predicting the weight-loss ratio of damaged fragrant pears(R^(2)=0.9929;RMSE=0.2138).It has also been proved to have good predictive effect in production practice(R^(2)=0.9377,RMSE=0.7138).The research findings can provide references to predict the delivery quality and time of delivery of Korla fragrant pears.

Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats:possible role of decreased lecithin cholesterol acetyl transferase activity

Objective:To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats.Methods:Administration of dexamethasone was given at 10 mg/kg,sc.to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index.Results:Lemongrass oil(100 and 200 mg/kg,po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg,po.The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase(LCAT) activity.Conclusions:These results suggested that Lemon gross oil possess significant antihyperlipidemic activity.

Influences of blood lipids on the occurrence and prognosis of hemorrhagic transformation after acute cerebral infarction: a case-control study of 732 patients

Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.

Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic and lipid-lowering efficacy

Based on a non-competitive and selective PTP1 B inhibitor reported by us previously, thirtynine benzamido derivatives were designed and synthesized as novel PTP1 B inhibitors. Among them,twelve compounds exhibited IC_(50) values at micromolar level against human recombinant PTP1 B, and most of them exhibited significant selectivity to PTP1 B over TC-PTP and CD45. Further evaluation of the most potent compound 27 on high-fat diet(HFD)-induced insulin-resistant(IR) obese mice indicated that27 could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.& 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).