Reduction In Tg Research Articles

The role of poly (ethylene-co-methacrylic acid) (EMAA) on cure kinetics and thermomechanical properties of epoxy

The addition of thermoplastic to thermosetting matrix systems has been proposed as a successful strategy to produce polymers with self-healing ability. Curing mechanism of diglycidyl ether of bisphenol A/triethylene-tetramine epoxy system modified with poly(ethylene-co-methacrylic acid) (EMAA) thermoplastic healing agent was investigated in this work. The effects of thermoplastic content, particle size and dispersion on thermomechanical properties were studied. Specimens were produced with 5 wt. %, 10 wt. % and 15 wt.% EMAA with particle sizes ≤ 125 μm or ≤ 425 μm. The addition of thermoplastic produced a reduction in E’ of about 27% for samples with particles ≤ 125 μm and about 45% for samples with particles ≤ 425 μm. Samples with particle size ≤ 125 μm showed a reduction in Tg of up to 37 °C as compared to neat epoxy. In the case of samples with particle size ≤ 425 μm, no direct correlation between Tg and mass fraction of added EMAA is found. Thus, particle size played an important role on thermomechanical properties and cure kinetics of epoxy. The greater the interfacial area, the greater was the change in final properties as compared to the unmodified material. It was also observed that the mass fraction and particle size can interfere in the curing reactions, where results suggest deceleration when smaller particles (≤ 125 μm) are added in larger fractions and acceleration with increasing mass fraction of larger particles (≤ 425 μm). All experimental reactions could be fit to the autocatalytic Sourour and Kamal model with good agreement; the model was able to predict the effects of thermoplastic addition in different particle sizes and mass fractions.

Stability of nitrile and vinyl latex gloves under repeated disinfection cycles

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission by fomites is one of the main concerns of coronavirus disease 2019, the World Health Organization advised on the use of protective gloves for handling contaminated surfaces and fomites. The shortage in the supply of personal protective equipment (PPE) due to the surging demand in conjuncture with the disposal of an unprecedented quantity of contaminated PPE into the landfill led to an interest for alternative platforms for the management of PPE. In this study, we evaluated the potential of reusing gloves after repeated disinfection cycles using six readily available and common sterilization methods: UV, ethanol, heat, steam, bleach, and quaternary ammonium compounds (quats) for the inactivation of SARS-CoV-2. For this, two commercially available medical-grade gloves, i.e. nitrile and vinyl (polyvinyl chloride) gloves were tested. Both types of gloves showed deterioration in mechanical and thermal performance with the use of quats as sterilization treatment while no remarkable change in properties was observed up to 20 cycles of disinfection for the other sterilization methods. The exceptions were that the vinyl and nitrile gloves did not tolerate steam/dry heat and UV treatment over 10 cycles due to likely dehydrochlorination and thermal degradation, respectively. Subsequent rounds of sterilization caused no significant change in the glass transition temperature (Tg) of either medical gloves; however, quats caused a slight reduction in Tg due to its plasticizing effect. Overall, the physical sterilization treatments including steam, dry heat, and UV allowed the gloves to retain their thermomechanical performance up to ten cycles of sterilization.

Effect of the normalization of TSH and free T4 on lipid profile in a pediatric population with primary hypothyroidism.

Hypothyroidism has been associated with dyslipidemia. Its treatment with levothyroxine has shown a positive effect on the lipid profile in adults, however, there is a lack of data on the pediatric popu lation. to evaluate the effect of the thyroid profile normalization on the lipid profile in children with primary hypothyroidism. Retrospective study in children aged from 6 to 16 years, with diagnosis of primary hypothyroidism due to Hashimoto's thyroiditis, in treatment with levothyroxine, and who had an evaluation of serum lipids before and during their treatment. The lipid profile was evaluated in 2 stages: the first one referred to as "before levothyroxine treatment" (at the diagnosis of primary hypothyroidism) and the second one referred to as " thyroid profile normalization" (when normalization of Thyroid-stimulating hormone [TSH] and free T4 [FT4] was achieved during levothyroxine treatment). Sociodemographic and anthropometric data were recorded. The lipid profile evaluation consisted of the serum determination of total cholesterol (TC), high-density cholesterol (HDL-C), and TG. The phenotype of dyslipidemias was determined according to the Fredrickson's classification. 72 patients were included (61% women; age 11.5 ± 2.9 years), out of which 58.3% (n = 42) presented pre-treatment dyslipidemia. In hypothyroid state, it was evident the correlation of TSH with TC (r = 0.36; p = 0.002), LDL-C (r = 0.46; p = 0.01), and HDL-C (r = -0.33; p = 0.004). The thyroid profile normalization showed the reduction of TC [184 mg/dL (IQR 92-322) vs 147 mg/dL (IQR 92-283); p = 0.05], LDL-C [99 mg/dL (IQR 44-232) vs 82 mg/dL (IQR 41-168); p = 0.02], TG [113 mg/dL (IQR 50-483) vs 88 mg/dL (IQR 16-343); p = 0.03], and the frequency of dyslipidemia [58.3% vs 22.2%; p = 0.001), as well as the TC correction with TG (r = 0.35; p = 0.02) and LDL-C (r = 0.88; p = 0.01). Persistent dyslipidemia was associated with obesity (r = 0.27; p = 0.02), overweight (r = 0.58; p = 0.001), and pre-treatment dyslipidemia (r = 0.53; p = 0.001). There is an association between TSH, TC, LDL-C, and HDL-C in hypothyroidism. When the thyroid profile was normalized, there was a reduction of TC, TG, LDL- C, and dyslipidemia frequency. Persistent dyslipidemia was associated with obesity, overweight, and pre-treatment dyslipidemia.

The effect of intermittent fasting on mortality in patients with type 2 diabetes and metabolic disease with high cardiovascular risk: a systematic review

Background. Intermittent fasting (IF) is a modern method of modifying eating behavior in patients who cannot tolerate calorie restriction. Intermittent fasting is effective in weight loss and has different types, which allows patients to adopt the type they are most comfortable with. Intermittent fasting has positive effects on human health, and this can lead IF to be adopted in standard medical care. There is insufficient data on the effect of IF on mortality and health status in patients with comorbid pathology. The aims of this systematic review are to analyze and summarize data from original studies about IF and mortality in patients with type 2 diabetes, metabolic disease and high cardiovascular risk. Methods. Original studies published in the last 5 years were selected from MEDLINE via PubMed, Web of Science, Scopus and Google Scholar using PRISMA guidelines. Results. Twenty-nine original articles were selected and analyzed. Intermittent fasting showed a statistically significant reduction in BMI, LDL, TG, HDL and HbA1C. Data from this systematic review shows that IF is a safe and effective way of reducing BMI in patients with co-morbidities. Conclusion. Further long-term studies examining the effects of IF on mortality in co-morbid patients are needed.

Lipotoxic hepatocytes promote nonalcoholic fatty liver disease progression by delivering microRNA-9-5p and activating macrophages.

M1-polarized macrophages are involved in chronic inflammatory diseases, including nonalcoholic fatty liver disease (NAFLD). However, the mechanisms responsible for the activation of macrophages in NAFLD have not been fully elucidated. This study aimed at investigating the physiological mechanisms by which extracellular vesicles (EVs)-encapsulated microRNA-9-5p (miR-9-5p) derived from lipotoxic hepatocytes might activate macrophages in NALFD. After blood sample and cell collection, EVs were isolated and identified followed by co-culture with macrophages. Next, the palmitic acid-induced cell and high fat diet-induced mouse NALFD models were established to explore the in vitro and in vivo effects of EVs-loaded miR-9-5p on NAFLD as evidenced by inflammatory cell infiltration and inflammatory reactions in macrophages. Additionally, the targeting relationship between miR-9-5p and transglutaminase 2 (TGM2) was identified using dual-luciferase reporter gene assay. miR-9-5p was upregulated in the NAFLD-EVs, which promoted M1 polarization of THP-1 macrophages. Furthermore, miR-9-5p could target TGM2 to inhibit its expression. Downregulated miR-9-5p in NAFLD-EVs alleviated macrophage inflammation and M1 polarization as evidenced by reduced levels of macrophage inflammatory factors, positive rates of CD86+ CD11b+, and levels of macrophage surface markers in vitro. Moreover, the effect of silencing of miR-9-5p was replicated in vivo, supported by reductions in TG, TC, AST and ALT levels and attenuated pathological changes. Collectively, lipotoxic hepatocytes-derived EVs-loaded miR-9-5p downregulated the expression of TGM2 and facilitated M1 polarization of macrophages, thereby promoting the progression of NAFLD. This highlights a potential therapeutic target for treating NAFLD.

Dispersion at Single Unit TiO2 Nanoparticles Reduced Tg, Induced Chain Disentanglement and Reduced Tensile Modulus in Waterborne Acrylic Coatings

AbstractSpatially distributed TiO2 nanoparticles induced an order of magnitude decrease of glass transition temperature, Tg, and chain disentanglement in waterborne acrylic coatings. Acrylic/TiO2 coatings are synthesized in situ by batch emulsion polymerization. The copolymer is based on butyl acrylate (BA), methyl methacrylate (MMA), and acrylic acid (AA) with composition 56:42:2 mol%, and nano‐TiO2 (ca. 12 nm) is incorporated up to 3 wt% content. Transmission electron microscopy (TEM) showed that TiO2 is dispersed at nearly single unit throughout the acrylic matrix. The nanoparticle reduced Tg and broadened the temperature range of the glass transition, δTg. The considerable increase of δTg suggests gradients of dynamics. Shear rheometry demonstrated that TiO2 induced chain disentanglement, the rubbery modulus Ge decreased two orders of magnitude with only 1 wt% TiO2 content thus increasing the packing length p (and the reptation tube diameter as dt = kp, k > 1). Consequently, the tensile Young's modulus E decreased an order of magnitude, relative to the neat copolymer. The reduction of Tg, the slowdown of macromolecular dynamics, the chain disentanglement and the increase of dt suggests dynamics modification due to intercalation of the entangled web by the TiO2 nanoparticles, and these results may be ascribed to a nanoconfinement effect.

Effect of Wheat Germ, Wheat Germ Oil on Lipid Profile of Hypercholesterolemic Rats

Hypercholesterolemia plays an important role in atherosclerosis and cardiovascular diseases (CVD) that represent one of the greatest worldwide medical problems nowadays. Recently, an increased attention/ interest for natural antioxidant/ hypercholesterolemia as WG/WGO is increasing. Wheat germ/ Wheat germ oil (WG/WGO) is an excellent source of essential and polyunsaturated fatty acids and vitamin E. It is one of the richest natural sources of tocopherol. This work aims to evaluate the effect of administration of wheat germ (WG) /wheat germ oil (WGO) for 6 weeks on serum lipid profile, lipid peroxidation (liver malondialdehyde) in hypercholesterolemic rats. One hundred and twenty maleSprague Dawelyrats weighing 180-192 gm were used in this study. They were randomly distributed into six groups (20 rats/ group) as follow: g1: normal control, G2: hypercholesterolemic rats; G3: Normal rats treated with WG; G4: hypercholesterolemic rats treated with WG; G5: Normal rats treated with WGO; G6: hypercholesterolemic rats treated with WGO for 6 weeks. Also WG was analysed for its nutritive value, while WGO was analysed for fatty acid profile, and studied for its physico-chemical properties. The results showed significant elevation of liver malondialdehyde (MDA) and serum lipid profile in untreated rats fed on hypercholesterolemic diet. Hypercholesterolemic rats treated with WG/WGO showed an improvement in the biochemical assay of their lipid profile compared with untreated hypercholesterolemic rats. WG/WGO may be able to protect against atherosclerosis and CVD. The administration of WG /WGO to diets of rats caused a marked reduction in TC, LDL-C, VLDL-C, TG and MDA. This improvement effect may be mediated via enhancement of the antioxidant defence system and other factors. However, further clinical studies on human beings are required to assess the efficacy and safety of the WG/WGO.

Liquid dewetting of ultrathin polystyrene films: Is there a molecular architecture effect?

AbstractWe have used a liquid dewetting method to investigate the glass transition temperature Tg of high molecular weight linear, long branched 3‐arm star, and short branched 8‐arm star polystyrene (PS) in the form of ultrathin films. The results of these dewetting experiments are consistent with prior studies of dewetting of linear PS films and show that, independent of molecular architecture, the glass transition temperature Tg reductions with decreasing film thickness, while important below about 20 nm, are weaker than those observed for linear PS supported on a rigid substrate and as well as those observed in freely standing films. The lack of a strong molecular architecture effect on the Tg‐reductions is consistent with the Tg reductions for the dewetting from a liquid substrate reflects changes in segmental dynamics upon confinement rather than chain effects. This contrasts with changes, including increases seen in dewetting from a rigid substrate, for different molecular architectures reported in the literature.

Saroglitazar in patients with non-alcoholic fatty liver disease and diabetic dyslipidemia: a prospective, observational, real world study.

Saroglitazar, a dual peroxisome proliferator activated receptor α/γ agonist, approved for diabetic dyslipidemia (DD), is potential therapeutic option for non-alcoholic fatty liver disease (NAFLD). This prospective, observational, real-world study aimed to determine efficacy and safety of Saroglitazar in patients with NAFLD and DD. We included patients with DD and NAFLD who received Saroglitazar 4 mg once daily for 24 weeks. Blood investigations, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) (FibroScan) were compared at baseline and 24 weeks. Of 163 patients screened, 107 were included, and 101 completed 24 weeks treatment (mean age 50.4 ± 12.3 years, 78.5% males, mean body mass index 28.8 ± 4.2). After 24 weeks, alanine transaminase (ALT) reduced significantly from 94 (47–122) to 39 (31–49) (p < 0.0001) and aspartate aminotransferase (AST) (U/L) from 89 (43–114) to 37 (30–47) (p < 0.0001) and LSM (kPa) from 8.4 (7.1–9.3) to 7.5 (6.4–8.4) (p = 0.0261). CAP, glycated hemoglobin and lipid parameters also improved significantly. On linear regression, there was significant association between percent change in ALT and AST with TG reduction after treatment (p = 0.024 and 0.037 respectively).We conclude that Saroglitazar leads to significant improvement in transaminases, LSM, and CAP in NAFLD patients with DD.

THE EFFECTS OF LOW-DOSE ROSUVASTATIN ALONE OR IN COMBINATION WITH FENOFIBRATE OR OMEGA 3 FATTY ACIDS IN MIXED DYSLIPIDEMIA

Objective Mixed dyslipidemia is characterized by elevated cholesterol and triglycerides. Indians have high prevalence of this pattern. The aim of present study was to evaluate the effects of rosuvastatin and in combination with fenofibrate or omega-3-FAs on lipids and hsCRP. Methods This was an open-label randomized study. Patients were allocated to low-dose rosuvastatin(R), rosuvastatin plus fenofibrate (RF) or rosuvastatin plus omega-3-FA(RO). At 6-weeks and 12-weeks follow-up, lipid lowering effect and change in hsCRP was studied. Results The study involved 105 participants (M/F=68/37) with a mean age of 57±13 years. At end of 6 and 12-weeks, there was significant reduction in TC, LDL-C, TG and hsCRP in all treatment groups, but increase in HDL-C became significant at 12-weeks. Percentage reduction in TC was 21%vs17%vs23% at 6-weeks and 31%vs37%vs35% at 12-weeks in group R, RF and RO, respectively. At 12-weeks, reduction in LDL-C was 22% in R vs 45% in RF vs 18% in RO and increase in HDL-C was 3.8% in R vs 7.6% in RF vs 15.8% in RO. Percentage reduction in triglycerides was 18%vs31% vs30% at 6 weeks and 23%vs52%vs51% at 12-weeks. Conclusion The mixed dyslipidemic patients responded well in terms of significant reduction in TC, LDL-C, and improving HDL-C and inflammation across all study groups. However, combination of low-dose-rosuvastatin plus fenofibrate or omega-3-FAs had more potent effect in reducing triglycerides and also in percentage increase in HDL-C, when compared with rosuvastatin alone. Omega-3 FAs, therefore, seem to be an attractive alternative to fibrates in patients with mixed dyslipidemia.

Pectin and mango pulp both reduce plasma cholesterol in pigs but have different effects on triglycerides and bile acids

The aim of this study was to investigate the mechanisms of action of pectin as an extract (from apple) and as a major part of fruit pulp (mango) on plasma lipids and bile acids (BA). Pigs were used as a model for humans, and were divided into three groups (n = 10) fed a Control, pectin extract (Pectin) or mango pulp (Mango) diet for 28 d. Plasma samples were taken at the beginning (D0) and at days 15 (D15) and 28 (D28) when digesta samples were also collected from different segments of the small intestine. At D28, compared to the Control, Pectin significantly decreased plasma total cholesterol (TC, 18.0%, P < 0.01) and LDL-C (17.2%, P < 0.05) and increased total BA (TBA; 4.1 μmol/L; P < 0.05). Mango decreased TC (9.5%, P < 0.05). Pectin significantly increased intestinal TBA (P < 0.01), decreased total neutral sterols (TNS) including cholesterol (P < 0.05), decreased fatty acid digestibility (P < 0.01) and decreased plasma triglycerides (TG, 28.5%, P < 0.01). However, Mango significantly increased plasma TG (31.1% P < 0.05) and intestinal TNS (P < 0.05). The increases in intestinal and plasma TBA with the Pectin but not Mango, suggests that the mechanism(s) by which pectin-rich components cause plasma TC, LDL-C and TG reduction differ for soluble and particulate forms. Furthermore, the prebiotic properties of both forms of pectin were shown to include changes in the BA profiles, with significant increases in the therapeutic BA, ursodesoxycholic acid (UDCA).

Heat Properties of Polylactic Acid Biocomposites after Addition of Plasticizers and Oil Palm Frond Microfiber

Polylactic acid (PLA) is a biopolymer that can replace thermoplastic polymers such as polypropylene (PP) in various applications due to strength, young modulus, biocompatibility, biodegradability, good clarity, oil resistance, and oxygen barrier ability. However, PLA has some drawbacks, including brittle, high glass transition temperature (Tg), and low degradation and crystallization rates. Therefore, modification is needed with the addition of nucleating agents and plasticizers to overcome these limitations of PLA. This research aims to study the effect of plasticizers and microfibril cellulose of oil palm frond (OPF) on thermal stability and to review the crystallization kinetics of PLA biocomposites. Polyethylene glycol and triacetin were used as plasticizers. Thermal analysis was performed using Thermal Gravimetry analysis (TGA) and Differential Scanning Calorimetry (DSC). The crystallization kinetics study was analyzed using a modified Avrami model under non-isothermal conditions. PLAP4000 has better thermal stability than PLAP200 and PLAG with Tonset and Tmax values reaching 349.17°C and 374.68°C, respectively, which are close to pure PLA. All types of plasticizers influenced decreasing the Tg value in the range of 27–42%, whereas OPF microfiber addition contributes to a Tg reduction of 37-55 %. Crystallization kinetic study was informed for heterogeneous and simultaneous nucleation mechanisms with an n value range of about 2-3 for PLAP4000 and PLAOP4000. The crystallization rate was multiplied 4-9-fold for PLAOP200 and 2-3-fold for PLAOP4000.

The effects of zinc supplementation on metabolic profile and oxidative stress in overweight/obese patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial

BackgroundEvidence indicates the positive effects of zinc on insulin resistance and oxidative stress in metabolic syndrome or diabetes. Non-alcoholic fatty liver disease (NAFLD) is the main hepatic manifestation of insulin resistance and metabolic syndrome. The present study is the first clinical trial that evaluated the effects of zinc supplementation on metabolic and oxidative stress status in overweight/obese patients with NAFLD undergoing calorie- restriction diet. Methods: Fifty six overweight/obese patients with confirmed mild to moderate NAFLD using ultrasonography were randomly allocated to receive 30 mg elemental zinc supplement (n = 29) or placebo (n = 27) along with weight loss diet for 12 weeks. Serum levels of zinc, homeostasis model of assessment-estimated insulin resistance (HOMA-IR), lipid profile, serum superoxide dismutas1 (SOD1) and malondialdhyde (MDA) levels were assessed. ResultsSerum levels of insulin, SOD1, MDA and HOMA-IR were improved in the treatment group (p < 0.05). Within group comparison showed significant reduction in serum FBS, HbA1C, TC, LDL-c and TG in the treatment group. Conclusion: Zinc supplementation for three months improved insulin resistance and oxidative stress status in overweight/obese NAFLD patients with no beneficial effects on lipid profiles over weight loss diet. Registration ID in IRCT (IRCT NO: 20181005041238N1).

Effect of saroglitazar 2\xa0mg and 4\xa0mg on glycemic control, lipid profile and cardiovascular disease risk in patients with type 2 diabetes mellitus: a 56-week, randomized, double blind, phase 3 study (PRESS XII study)

BackgroundThe potential for PPAR agonists to positively affect risk of cardiovascular disease in patients with type 2 diabetes (T2DM) is of persistent attention. The PRESS XII study primarily aimed to evaluate the efficacy and safety of saroglitazar (2 mg and 4 mg) as compared to pioglitazone 30 mg on glycemic control in patients with type 2 diabetes mellitus.MethodsIn this randomized double-blind study, patients with T2DM [glycosylated hemoglobin (HbA1c) ≥ 7.5%] were enrolled from 39 sites in India. Patients received once-daily doses of either saroglitazar or pioglitazone (1:1:1 allocation ratio) for a total of 24 weeks. Patients were continued in a double blind extension period for an additional 32 weeks. Efficacy evaluations of glycemic parameters [HbA1c (Primary endpoint at week 24), FPG and PPG] and other lipid parameters (TG, LDL-C, VLDL-C, HDL-C, TC, Non HDL-C, Apo A1 and Apo B) were conducted at week 12, 24 and 56 and compared to the baseline levels. The efficacy analyses were performed by using paired t-test and ANCOVA model.ResultsA total of 1155 patients were enrolled in this study. The baseline characteristics were similar between the three treatment groups. The within group mean (± SD) change in HbA1c (%) from baseline of the saroglitazar (2 mg and 4 mg) and pioglitazone treatment groups at week 24 were: − 1.38 ± 1.99 for saroglitazar 2 mg; − 1.47 ± 1.92 for saroglitazar 4 mg and − 1.41 ± 1.86 for pioglitazone, respectively. Statistically significant reduction from baseline in HbA1c was observed in each treatment group at week 24 with p-value < 0.016. There was a significant reduction in TG, LDL-C, VLDL-C, TC and Non HDL-C with a significant increase in HDL-C from baseline levels (< 0.016). Most of the AE’s were ‘mild’ to ‘moderate’ in severity and were resolved by the completion of the study.ConclusionsSaroglitazar effectively improved glycemic control and lipid parameters over 56 weeks in patients of T2DM receiving background metformin therapy and has a promising potential to reduce the cardiovascular risk in T2DM patients.Trial registration CTRI/2015/09/006203, dated 22/09/2015

Rapid prediction method of failure load for hygrothermally aged CFRP – Aluminum alloy single lap joints

This paper presents an experimental study on the durability of adhesively bonded carbon fiber reinforced polymer (CFRP) – aluminum alloy single lap joints (SLJs) that are undergoing hygrothermal degradation. The failure loads of hygrothermally aged joints were measured and the corresponding fracture surfaces were investigated via visual observation and SEM. The variations of the Tg and the chemical components were determined by the DSC and FTIR analysis, respectively. The results demonstrate that the failure load of joints decreases nonlinearly as the aging duration increases, which approximates the exponential function. Cohesive failure is dominated before and after aging, meanwhile, the moisture absorption plasticizes the adhesive and leads to rougher fracture surfaces. The reduction in Tg and the FTIR results support the occurrence of a hydrolysis reaction in the adhesive due to hygrothermal aging. By quantitatively studying the relationship between the failure loads and the absorbance intensities of functional groups, a failure load prediction method was proposed. This method can establish the correspondence relationship between accelerated aging and actual service aging based on the chemical characteristics of adhesive, and realize the residual performance prediction of the bonding structure after hygrothermal aging rapidly and easily.

945-P: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Cohort Study to Evaluate the Efficacy and Safety of 12 Once-Weekly Subcutaneous Doses of PB-119 to Patients with Type 2 Diabetes Mellitus as Monotherapy

Background: PB119 (polyethylene glycol exenatide) which is a novel once-weekly subcutaneous GLP-1RA, has good pharmacokinetic properties. As a GLP-1RA, it shows a good safety profile and provides solid glycemic control while doesn’t need dose titration. We aimed to assess the efficacy and safety of PB119 monotherapy in Chinese patients with T2DM. Methods: In this phase 2 study, we randomly assigned 251 patients (1:1:1:1) to receive 3 doses of PB119 (75ug, 150ug, 200ug) or dose-matched placebo using permuted-block randomization, with a block size of 12 and without stratification. Eligible patients were men or women (aged 18-70 years) with T2DM who had a BMI of 18.5-35.0 kg/m², were on a diet and exercise regimen and untreated at least 3 months prior to screening. The study started with a 4-week placebo run-in period followed by a 12-week treatment period. The primary endpoint was the change in HbA1c from baseline to week 12, which was assessed in all patients who received at least 1 dose of study drug and had both baseline and at least 1 post-baseline HbA1c value. Safety was assessed in all patients who received at least 1 dose of study drug. ClinicalTrials.gov NCT03520972. Findings: At the end of week 12, the least squares mean change in HbA1c from baseline was -0.39% (95% CI -0.60 to -0.19) in the placebo group, -1.11% (-1.32 to -0.91) in the 75ug group, -1.57% (-1.78 to -1.37) in the 150ug group and -1.41% (-1.61 to -1.20) in the 200ug group. Compared with the placebo group, the change in HbA1c between baseline and week 12 was significant in all PB119 (p&amp;lt;0.001) groups. Significant reductions in TC and TG were observed in 150ug and 200ug groups (P&amp;lt;0.05), while the reductions in body weight and LDL-C were significant in 200ug group (P&amp;lt;0.05). There were no reports of drug-related serious adverse events or severe hypoglycemia. Disclosure M. Xu: None.

1830-P: Therapeutic Effect of a Novel Long-Acting GLP-1/GIP/Glucagon Triple Agonist (HM15211) in CDHFD-Induced NASH and Fibrosis Mice

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease characterized by steatosis and inflammation, which results in fibrosis. In particular, advanced fibrosis due to NASH is associated with a high risk of liver-related mortality, becoming one main cause for liver transplant. To date, there are, however, no pharmacological therapy approved. One major hurdle for the drug development is limited pathologic features of current animal models, in terms of clinical relevance. The choline-deficient and high fat diet (CDHFD) mice have known to develop multiple aspects of NASH and fibrosis similarly with those in human, being increasingly recognized as a feasible disease model. HM15211 is a novel long-acting GLP-1/GIP/Glucagon triple agonist. Previously, HM15211 treatment improved liver fat and fibrosis in various animal models of NASH and fibrosis. Here, we further explored its efficacy in CDHFD mice. In CDHFD mice (8 wks induction), HM15211 significantly reduced hepatic TG and TBARS (oxidative stress marker). Histological analysis indicated a significant reduction both in hepatic inflammatory marker expression and NAFLD activity score. Of note, when compared to FXR agonist or ACC (acetyl CoA carboxylase) inhibitor, HM15211 treatment was associated with greater efficacy improvement. To further confirm, CDHFD mice with an extended induction period (up to 16 wks) was used. Despite the severe disease progression featured by advanced liver fibrosis, HM15211 reduced hepatic hydroxyproline (-42% vs. vehicle) and sirius red positive area (11.9% vs. 4.1% for vehicle and HM15211) markedly in addition to significant liver TG reduction (66.2% vs. vehicle). Therefore, consistent efficacy in various animal models including CDHFD mice suggests the beneficial effect of HM15211 on NASH and fibrosis. Efficacy studies in biopsy proven NASH patients are ongoing to assess the clinical relevance of these findings. Disclosure J. Choi: Employee; Self; Hanmi Pharmaceutical. J. Kim: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. H. Kwon: Employee; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. S. Bae: Employee; Self; Hanmi Pharmaceutical. D. Kim: Board Member; Self; Hanmi Pharmaceutical. I. Choi: Board Member; Self; Hanmi Pharmaceutical.

Efficacy of Common Spices on Improving Serum Lipids in Individuals with Type 2 Diabetes: Systematic Review and Meta-Analysis of Clinical Trials

Abstract Objectives This systematic review and meta-analysis explored efficacy of common spices cardamom, ginger, cumin, curcuminoids and cinnamon on improving serum lipid levels in people with type 2 diabetes. Methods Databases PubMed, FSTA, Web of Science, CINAHEL, MEDLINE and Cochrane Library database of systematic review were searched using keywords (“Serum lipids” OR triglyceride* OR cholesterol* OR “LDL” OR “HDL” OR dyslipidemia) AND (Ginger or zingiber or “zingiber officinale” or “cinnamomum zeylanicum” or “cinnamomum aromaticum” or “cinnamomum cassia” or “cinnamomum verum” or curcumin or turmeric or curcuminoids or “curcuma longa” or langas or “curcuma zedoarias” or turmeric) AND (diabetes* OR “diabetes mellitus” OR “type 2” OR “blood glucose” OR insulin* OR antidiabet* OR "glucose level”) up to January 2020. Statistical calculations used SAS software version 9.2 (SAS, Cary NC, USA). Results Of 636 studies, 27 met the meta-analysis selection criteria, with 5698 trial participants total. The spices significantly improved TC, TG, and LDL-C, with no significant effect on HDL-C. The reduction in intervention vs. control was: TC, −5.0912 mg/dl, 95% CI (−18.7167, −0.7804), P value 0.038; TG, −9.7486 mg/dl, 95% CI (−33.9445, −5.8260), P value 0.33; LDL-C, −4.653 mg/dl, 95% CI (−8.686, −0.6212), P value 0.02. No significant effect on HDL-C was seen (−0.019 mg/dl, 95% CI (−0.72, 0.68), P = 0.95. Heterogeneity was observed across all 27 studies. Conclusions Spices examined exhibited a significant reduction in TG, TC and LDL-C levels among patients with type 2 diabetes with no effect on HDL-C levels suggesting a role for spices as a dyslipidemic agent. Funding Sources Clemson University.

Structural Elucidation of Isolated Phytochemicals from Selected Medicinal Plants with Antihyperlipidemic Activity and Development of Polyherbal Formulation with Densitometric Analysis of Isolated Phytoconstituents

Abstract: Objectives: The present systematic research aimed to express the antihyperlipidemic effects of different types of herbs based on animal studies. The purpose of the present project is to perform the phytochemical investigation and exploration of hypolipidemic activity with the development and quantification of phytoconstituents of polyherbal hypolipidemic formulation employing Apium graveolens, Salvadora persica, Carica papaya and Evolvulus alsinoides. Materials and Methods: Flash chromatography technique was used for the isolation of phytoconstituents from the selected medicinal plants. Antihyperlipidemic study was done on triton induced model. Triton- WR 1339 (400 mg/kg b.w) i.p. injection were given to different animal groups. HPTLC densitometric method was established for the quantification of the phytoconstituents in polyherbal formulation. Results: The phytoconstituents so isolated were identified as 8, 8-Dimethyl-2H, 8H-pyrano [2, 3-f] chromen-2-one, 9- methoxyfuro [3, 2-g] chromen- 7-one, 7- hydroxy-2H-chromen -2-one, Isothiocyanatomethylbenzene and 17-(5-Ethyl- 6-methylheptan-2-yl)-10,13-dimethyl2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro 1Hcyclopenta[α]phenanthren-3-ol through chromatographic separation techniques and their structures were elucidated by spectroscopic analysis. The formulation showed significant reduction in TC, TG, LDL and VLDL level (p<0.01) and significantly raised HDL level (p<0.01) compared to hyperlipidemic group. Furthermore, HPTLC method was established for the quantification of isolated phytoconstituents in polyherbal formulation through densitometric analysis. Conclusion: The present work also characterized active phytoconstituents from different parts of selected plants. The research work involved development of polyherbal hypolipidemic formulation with a view to reduce the serum levels of TC, TG, LDL and to increase the serum level of HDL cholesterol and to establish HPTLC densitometric method for quantification of its phytoconstituents. Key words: Hyperlipidemia, Medicinal Plants, Flash Chromatography, Isolated Phytoconstituents, HPTLC Densitometric Analysis.

The effectiveness of acupoint catgut embedding in hyperlipidemia with obesity: Protocol for a systematic review and meta-analysis.

Hyperlipidemia is a common disease characterized as blood lipid metabolism disorders, which is always companied with obesity. Hyperlipidemia is the leading cause of the cardiovascular disease (CVD) closely associated with mortality, and the risk can further elevate in the obese population. Additionally, it induces stroke and acute pancreatitis. Studies demonstrated that acupoint catgut embedding is an effective therapy for hyperlipidemia with obesity. Whereas, there is no systematic review and meta-analysis to support the point. Thus, we intend to conduct a systematic review and meta-analysis to testify its effectiveness in hyperlipidemia with obesity. We will include articles by searching the following database: PubMed, Embase, Web of Science, Cochrane Controlled Trials Register (CENTRAL), China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Chinese Science Journal Database (VIP), and Wanfang database. Whats more, the manual search can be executed as the complement of database searching. Endnote X8 and RevMan V.5.3 will be used to complete the process of study selection, data analysis, as well as date management. The primary outcomes contain the reduction of TC, TG, LDL-C, HDL-C, and BMI, body weight (WB), waist circumference(WC), body fat percent (F%) from baseline to the end of studies. The second outcome is the number of adverse events during the total trial. We will summarize sufficient evidence to confirm the therapeutic effect and safety of acupoint catgut embedding in hyperlipidemia with obesity. INPLASY202040036.