Lower Blood Cholesterol Research Articles

Flow-mediated dilation reference values for evaluation of endothelial function and cardiovascular health.

Endothelial function is essential for cardiovascular health, and flow-mediated dilation (FMD) is an established technique to measure it. This paper aims to assess FMD values in apparently healthy individuals and provides reference values to facilitate wider clinical use. In 1,579 apparently healthy individuals (aged 18-76), fasted FMD values (data from 44 studies, 6 institutions, 22 operators) were normally distributed and inversely univariately correlated with age, body mass index, glucose, cholesterol, blood pressure, and brachial artery (BA) diameter. Significant multivariate predictors of FMD were age (-0.4%/decade), BMI (0.04%/kg/m2), smoking (-0.7%), and BA diameter (-0.44%/mm) that together explained 19% of the variability independent of operator, institution or ultrasound machine. Individuals in the high FMD tertile (>6.8%) were younger, had smaller BA diameter, lower blood pressure and cholesterol. In individuals with low- and intermediate fatal cardiovascular risk (SCORE), 26% and 53% of individuals, respectively, had FMD values in the low tertile (<5.4%). After adding data from 385 patients with stable coronary artery disease (CAD), ROC analysis (c = 0.841, P < 0.001) showed that FMD of >6.5% excluded CAD (95% sensitivity; 60% specificity) and FMD <3.1% excluded 95% healthy individuals (95% specificity, 31% sensitivity). A meta-analysis and meta-regression of 82 clinical trials (11 countries, n = 3,509) using similar FMD methodology showed that despite considerable heterogeneity (I2 = 0.97) FMD in healthy individuals was on average 6.4% (95%CI: 6.2%, 6.7%) with no significant differences between countries but a significant age-dependent decline (-0.3%/decade, R2 = 0.13). We provide an age-adapted frame of FMD reference intervals in apparently healthy individuals for use as a biomarker of cardiovascular health. As the degree of vascular endothelial function integrates environmental and genetic factors with classical CV risk factors, FMD may more comprehensively classify individuals with and without standard modifiable cardiovascular risk factors and serve as a target for cardiovascular prevention.

Pomegranate Peel Extract Decreases Plaque Necrosis and Advanced Atherosclerosis Progression in Apoe -/- Mice.

Atherosclerosis is a chronic lipid-driven inflammatory condition of the arteries and is a leading cause of stroke, myocardial infarction, and other peripheral arterial diseases. Plant products rich in polyphenols such as pomegranate juice and peel extract are known to have beneficial effects in suppressing atherogenesis. However, the mechanism of action and its effect on advanced atherosclerosis progression which results in adverse clinical outcomes are not well understood. Herein, we use a standardized hydroethanolic extract of Punica granatum (pomegranate) peel in the Apoe -/- a murine model of advanced atherosclerosis. It was observed that the pomegranate peel extract fed mice have decreased plaque necrosis and elevated lesional collagen content which was associated with a favorable metabolic profile including lowering of blood glucose, cholesterol, and triglyceride. The decrease in plaque necrosis was linked with increased lesional macrophage efferocytosis efficiency which was associated with enhanced expression of the efferocytosis receptor Mertk. Using in vitro studies, we show that pomegranate peel extract blocks the shedding of Mertk and preserves macrophage efferocytosis efficiency. These data identify a novel mechanism by which pomegranate peel extract promotes the resolution of inflammation in atherosclerosis.

THE EFFECT OF GIVING TOMATO JUICE IN REDUCING CHOLESTEROL LEVELS ON MENOPAUSE IN BPM NURUL UMAIRA TITI PAPAN, MEDAN DELI DISTRICT

Cholesterol is a fatty substance in the blood that is needed by the body for the formation of cell walls. Excessive fat can cause coronary heart disease which occurs in the elderly, especially in women who have passed menopause due to a decrease in the activity of the hormones estrogen and progesterone which has an impact on increasing cholesterol levels in the body. One non-pharmacological treatment is to consume tomato juice.This Research Objective To determine the effect of giving tomato juice on reducing cholesterol levels in menopause at BPM Nurul Umaira Titipapan, Medan Deli District. The Research method is a Quasi-experimental design with a pre-post test design. The study was conducted in February-May 2021. The population of this study was menopause who did cholesterol checks at BPM Nurul Umaira Titi papan, Medan Deli District. The sample is 15 people, by Total sampling. The independent variable is menopause, the dependent variable is the cholesterol levels of menopause. The research instrument used an Observation Sheet. Processing of statistical test data Sample T-Test. Research results are showing the difference between pre and post-giving tomato juice obtained an average value of 4.667 with Std. Deviation 41,593 with 95% CI 1,367-28,700. The results of the Independent t-Test to determine the difference in the average value of blood cholesterol levels between the intervention group and the control group obtained a p-value of 0.001 (p&lt;0.05). meaning that there is an effect of giving tomato juice to lower blood cholesterol levels. Conclusion: It can be concluded that tomato juice can help lower blood cholesterol levels in menopause

Clinical and Laboratory Features in the Israeli Population with COVID-19 Infection after Pfizer-BioNTech mRNA Booster Vaccination.

Background: Immune protection following either vaccination or infection with SARS-CoV-2 decreases over time. Objective: We aim to describe clinical and sociodemographic characteristics associated with COVID-19 infection at least 14 days after booster vaccination in the Israeli population. Methods: We conducted a population-based study among adult members of Leumit Health Services (LHS) in Israel. Nasopharyngeal swabs were examined for SARS-CoV-2 by real-time RT-PCR. The hematological and biochemical parameters in the peripheral blood before booster vaccination were evaluated. Results: Between 1 February 2021 and 30 November 2021, 136,683 individuals in LHS were vaccinated with a booster (third dose) of the BNT162b2 vaccine. Of these, 1171 (0.9%) were diagnosed with COVID-19 by testing positive for SARS-CoV-2 RT-PCR at least >14 days after the booster vaccination. The COVID-19-positive group was characterized by higher rates of chronic kidney disease than the matched COVID-19-negative group (43 (3.7%) vs. 3646 (2.7%); p = 0.039). Anemia, lower peripheral blood lymphocytes, monocytes, basophils, C3 Complement, cholesterol, and prothrombin time were also associated with COVID-19 after booster vaccination. Conclusion: People with chronic kidney disease and anemia should be included in possible future annual SARS-CoV-2 vaccination recommendations.

Determination of Iron Content, Potassium, Calcium, and Sodium In Chinese Date Fruit (Ziziphus Jujuba Miller.) Fresh and Boiled In Atomic Adsorption Spectrophotometry

Chinese dates fruit are generally used by the people of Indonesia as a fruit that has a fairly good nutritional value, namely every 100 g of Chinese dates fruit contain 79 kcal of energy, 1.2 g protein, 20.23 g carbohydrates, 250 mg potassium, 21 mg calcium, 23 mg. phosphorus, 0.5 mg iron, 3 mg sodium, 10 mg magnesium, 0.1 vitamin B6 and 69 mg vitamin C. Chinese dates fruit are foods that are rich in fiber, so they can lower blood cholesterol and cure chronic constipation. In addition, Chinese dates fruit are foods with good sources of potassium. Adequate potassium intake can lower blood pressure so that it can reduce the risk of cardiovascular disease. High iron content can also prevent anemia. The purpose of this study was to determine the differences in the content of iron, potassium, calcium, and sodium in fresh and boiled Chinese dates fruit fruit, and to determine the percentage decrease in levels after boiling.&#x0D; The method used in this study included dry digestion, then quantitative analysis of iron, potassium, calcium, and sodium was carried out using the Atomic Absorption Spectrophotometry (AAS) method, namely iron at a wavelength of 248.3 nm, for potassium 766.5 nm, to calcium 422.7 nm, and sodium 589.0 nm.&#x0D; The results showed that the iron content in fresh Chinese dates fruit fruit was (0.6687 ± 0.0084) mg/100 g and boiled (0.3285 ± 0.0127) mg/100 g. Potassium levels in fresh Chinese dates fruit fruit (657.9024 ± 0.4713) mg/100 g and boiled (158.6504 ± 0.2510) mg/100 g. Calcium levels in fresh Chinese dates fruit fruit were (47.3501 ± 1.1630) mg/100 g and boiled (26.3968 ± 0.5922) mg/100 g, and sodium levels in fresh Chinese dates fruit fruit (16.1272 ± 0.1543) mg/100 g and boiled at (13.4048 ± 0.1973) mg/100 g. The percentage decrease in mineral content in Chinese dates fruit fruit after boiling, for iron was 50.87%, potassium 75.88%, calcium 44.25%; and 16.88% sodium.&#x0D; Statistically different test of the average mineral levels of iron, potassium, calcium, and sodium using the T distribution, it can be concluded that fresh Chinese dates fruit fruit contain higher levels of iron, potassium, calcium, and sodium minerals than boiled Chinese dates fruit.&#x0D;

PKM JANTUNG PISANG CAMILAN SEHAT IBU MENYUSUI

Banana is one of Indonesia's leading commodities. Harvested area and banana production always occupy the first position. In 2012 the total production was 6,189,043 tons and the banana harvested area in Indonesia reached 103,157 hectares, with a productivity of 59.99 tons/ha. Indonesia itself is the fourth largest banana producing country in the world. Banana flowers have many health benefits, including high fiber content, low protein and fat, and a source of minerals such as magnesium, iron and copper. Dietary fiber is known to be useful for lowering blood cholesterol levels, normalizing blood glucose and insulin levels so that it is good for consumption by people with diabetes mellitus. In addition, banana heart has a very high antioxidant activity, most of which comes from anthocyanin compounds which are included in the flavonoid and polyphenol groups. The purpose of this activity is to explore innovative ideas, increase creativity, instill an entrepreneurial spirit, train mentally and teach to work hard and be responsible. In addition, another goal is to reduce the waste generated by processing them into banana heart chips and banana heart chips. There are several obstacles faced, namely (1) Limited capital. (2) Low motivation for entrepreneurship with banana heart as the main ingredient. (3) There is no diversity of banana heart products. (4) There is no packaging and marketing of banana blossoms.&#x0D; Keywords: various processed banana heart, marketing and income&#x0D;

Potential Granule Effervescent from a mixture of beetroot extract (Beta vulgaris L), Malang apple (Malus sylvestris L.) and Carrot (Daucus carota L.) as Preparation for Lowering Blood Cholesterol Levels

Potential Granule Effervescent from a mixture of beetroot extract (Beta vulgaris L), Malang apple (Malus sylvestris L.) and Carrot (Daucus carota L.) as Preparation for Lowering Blood Cholesterol Levels

The biological relevance of PCSK9: when less is better….

Proprotein Convertase Subtilisin/Kexin-type 9 (PCSK9) is a circulating negative regulator of hepatic low-density lipoprotein receptor (LDLR), which clears cholesterol from blood. Gain-of-function genetic mutations that amplify PCSK9 activity have been found to cause potentially lethal familial hypercholesterolemia. Inversely, reduction of its activity through loss-of-function genetics or with pharmaceuticals was shown to increase hepatic LDLR, to lower blood cholesterol, and to protect against cardiovascular diseases. New epidemiological and experimental evidence suggests that this reduction could also attenuate inflammation, reinforce cancer immunity, provide resistance to infections, and protect against liver pathologies. In this review, we question the relevance of this protein under normal physiology. We propose that PCSK9 is an important, but nonessential, modulator of cholesterol metabolism and immunity, and that its pathogenicity results from its chronic overexpression.

Changes in heart failure management and long-term mortality over 10 years: observational study

ObjectivesTo estimate the long-term survival of two cohorts of people diagnosed with heart failure 10 years apart and to assess differences in patient characteristics, clinical guideline compliance and survival by...

Evaluation of Antihyperlipidemic activity of leaves of Cassia tora

Aim: To evaluate the antihyperlipidemic activity of leaves of cassia tora Objective: Hyperlipidemia is a clinical condition causing lethal diseases like atherosclerosis, myocardial infarction etc that ultimately leads to death. Several works have been reported that the extracts of many plants have antihyperlipidemic activity. Cassia tora is used for a long time as a daily vegetable in many countries. It consists of phytochemical constituents like flavonoids which lowers blood cholesterol level. Materials and Methods: Materials used: Antihyperlipidemic activity of Cassia tora was screened by a model, Cholesterol diet induced hyperlipidemia. Marker enzymes like LDH, LDL, VLDL, total protein, total cholesterol, AST, ALP, ALT,SOD, Catalase, LPO and histopathology of myocardium and aorta carried out. Results: Flavonoids of leaves of Cassia tora treated group showed significant decrease in LDL-Cholesterol, total cholesterol, triglycerides, AST, ALT, ALP and increase in HDL cholesterol, albumin, total protein and further was concluded by histopathological studies. Conclusion: From result, it was concluded that flavonoid of leaves of Cassia tora shows antihyperlipidemic activity in the heart of rats.

ANTOCYANES FROM CLITORIA TERNATEA FLOWERS

The paper shows the promising feasibility of using the clitoral ternary Clitoria ternatea L. in the food industry. The main color molecules of C. ternatea flowers are various anthocyanins derived from the main classes of dolphinidin, such as ternatine. The blue color of flowers contains anthocyanins, which are widely used as a natural source of food dyes. The main properties of anthocyanins - adaptogenic, antispasmodic, anti-inflammatory and stimulating functions; antiallergic action; bactericidal, choleretic, sedative, hemostatic, antiviral properties; insulin-like, photosensitizing action; reduction of fragility and permeability of capillaries, increase of elasticity of vessels; lowering blood cholesterol; increase visual acuity, normalize intraocular pressure; strengthening the body's immunity and protective functions. Anthocyanin dyes of phenolic nature, which belong to bioflavonoids, occupy a special place among biologically active substances in plant raw materials of the clitoral triad. They determine the color of flowers from blue to blue. These plant pigments - anthocyanins - are well soluble in water. The most important factors on which the stability of anthocyanins depends are enzymes, temperature, oxygen, pH, heavy metal ions, ascorbic acid, light, etc. The intensity and variety of color in food depends on the acid content and pH. The same anthocyanins in an acidic environment give a red color, when the pH is shifted to the alkaline side give a blue or purple color, and in a strongly alkaline environment - green. Anthocyanins of flowers сlitoria ternatea L. can be used as a blue food coloring in acidic and neutral foods, in order to restore and increase the intensity of natural color, coloring colorless products and give them an attractive and marketable appearance.

Production, Characterization, Delivery, and Cholesterol-Lowering Mechanism of Phytosterols: A Review.

Phytosterols are natural plant-based bioactive compounds that can lower blood cholesterol levels and help prevent cardiovascular diseases. Consequently, they are being utilized in functional foods, supplements, and pharmaceutical products designed to improve human health. This paper summarizes different approaches to isolate, purify, and characterize phytosterols. It also discusses the hypolipidemic mechanisms of phytosterols and their impact on cholesterol transportation. Phytosterols have a low water-solubility, poor chemical stability, and limited bioavailability, which limits their utilization and efficacy in functional foods. Strategies are therefore being developed to overcome these shortcomings. Colloidal delivery systems, such as emulsions, oleogels, liposomes, and nanoparticles, have been shown to be effective at improving the water-dispersibility, stability, and bioavailability of phytosterols. These delivery systems can be used to incorporate phytosterols into a broader range of cholesterol-lowering functional foods and beverages. We also discuses several issues that need to be addressed before these phytosterol delivery systems can find widespread commercial utilization.

Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis

BackgroundMultiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) commonly affecting young adults. There is increasing evidence that environmental factors are important in the development and course of MS. The metabolic syndrome (MetS) which comprises dyslipidemia has been associated with a worse outcome in MS disease. Furthermore, the lipid-lowering drug class of statins has been proposed to improve MS disease course. However, cholesterol is also rate-limiting for myelin biogenesis and promotes remyelination in MS animal models. Thus, the impact of circulating blood cholesterol levels during the disease remains debated and controversial.MethodsWe assessed the role of circulating cholesterol on the murine model of MS, the experimental autoimmune encephalomyelitis (EAE) disease using two different approaches: (1) the mouse model of familial hypercholesterolemia induced by low-density lipoprotein receptor (LDLr) deficiency, and (2) the use of the monoclonal anti-PCSK9 neutralizing antibody alirocumab, which reduces LDLr degradation and consequently lowers blood levels of cholesterol.ResultsElevated blood cholesterol levels induced by LDLr deficiency did not worsen clinical symptoms of mice during EAE. In addition, we observed that the anti-PCSK9 antibody alirocumab did not influence EAE disease course, nor modulate the immune response in EAE.ConclusionsThese findings suggest that blood cholesterol level has no direct role in neuro-inflammatory diseases and that the previously shown protective effects of statins in MS are not related to circulating cholesterol.

Hypoglycemic and Antihyperlipidemic effects of Syzygium cumini (Lamarck) Skeels and Syzygium paniculatum (Gaertn.)

Introduction: there is a recent increase in interest in the use of medicinal and phytotherapeutic plants. Objective: to verify the effect of ethanolic extracts from different parts of fruits of two species of the genus Syzygium, on glucose and lipid levels in the blood, using animal models. Results: the bark extract of the seeds of S. cumini (Lamarck) Skeels proved to be effective in reducing blood glucose levels. This same extract was also effective in lowering blood cholesterol levels. The extract from the seed nuclei of S. cumini (Lamarck) Skeels and S. paniculatum(Gaertn) were effective in reducing blood triglyceride levels. Extracts from all parts of the fruits of S. cumini (Lamarck) Skeels and of the seed nuclei of S. panic-ulatum (Gaertn) prevented weight gain in the animals. Conclusion: in general, the seed extract of both species showed a direct influence on the parameters and characteristics under study.

The Effect of Simvastatin on Acute Phase Functional Outcome of Ischemic Stroke

Introduction: Stroke is one of the leading causes of death and disability worldwide, and especially in Indonesia. Several studies showed the pleiotropic and neuroprotective effect of simvastatin in addition to lowering blood cholesterol levels. Objective: This trial was conducted to investigate if the administration of simvastatin in acute ischemic stroke management can improve functional outcomes. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in patients with acute ischemic stroke with an NIHSS score of 4-14. Participants were randomly assigned to receive 40 mg of simvastatin or placebo for seven days. The NIHSS scale was compared on admission day, 4th and 8th day after administration of simvastatin between the two groups. Results: 52 individuals were randomized: 28 to simvastatin and 24 to placebo. There was no significant improvement of functional outcome between the two groups (p &gt; 0.05). Conclusion: Administration of simvastatin had no significant effect on outcome (measured by NIHSS) in patients with acute ischemic stroke.

Recent research progress of biologically active peptides.

With the rapid development of molecular biology and biochemical technology, great progress has been made in the study of peptides. Peptides are easy to digest and absorb, with lowering of blood pressure and cholesterol, improving immunity, regulating hormones, antibacterial, and antiviral effects. Peptides also have physiological regulation and biological metabolism functions with applications in the fields of feed production and biomedical research. In the future, the research focus of bioactive peptides will focus on their efficient preparation and application. This article introduces a comprehensive review of the types, synthesis, functionalization, and bio-related applications of bioactive peptides. For this aim, we introduced in detail various biopeptides and then presented the production methods of bioactive peptides, such as enzymatic synthesis, microbial fermentation, chemical synthesis, and others. The applications of bioactive peptides for anticancers, immune therapy, antibacterial, and other applications have been introduced and discussed. And discussed the development prospects of biologically active peptides.

Simple Nutrient-Based Rules vs. a Nutritionally Rich Plant-Centered Diet in Prediction of Future Coronary Heart Disease and Stroke: Prospective Observational Study in the US.

To better understand nutrition paradigm shift from nutrients to foods and dietary patterns, we compared associations of a nutrient-based blood cholesterol-lowering diet vs. a food-based plant-centered diet with risk of coronary heart disease (CHD) and stroke. Participants were 4701 adults aged 18–30 years and free of cardiovascular disease at baseline, followed for clinical events from 1985 and 86 to 2018. A plant-centered diet was represented by higher A Priori Diet Quality Score (APDQS). A blood cholesterol-lowering diet was represented by lower Keys Score. Proportional hazards regression was used to calculate hazard ratios (HR). Higher APDQS showed a nutrient-dense composition that is low in saturated fat but high in fiber, vitamins and minerals. Keys Score and APDQS changes were each inversely associated with concurrent plasma low-density lipoprotein cholesterol (LDL-C) change. Over follow-up, 116 CHD and 80 stroke events occurred. LDL-C predicted CHD, but not stroke. APDQS, but not Keys Score, predicted lower risk of CHD and of stroke. Adjusted HRs (95% CIs) for each 1-SD higher APDQS were 0.73 (0.55–0.96) for CHD and 0.70 (0.50–0.99) for stroke. Neither low dietary fat nor low dietary carbohydrate predicted these events. Our findings support the ongoing shift in diet messages for cardiovascular prevention.

Therapeutic properties of isoliquiritigenin with molecular modeling studies: investigation of anti-pancreatic acinar cell tumor and HMG-CoA reductase inhibitor activity for treatment of hypercholesterolemia.

Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have anti-tumor activity in vitro and in vivo. HMG-CoA reductase inhibitors, called statins, are used to reduce the risk of heart disease by lowering blood cholesterol levels. HMG-CoA reductase activity was determined according to the method described by Takahashi et al. The structure of human HMG-COA reductase in the resolution of 2.22 Å with the X-ray diffraction method (PDB ID: 1HWK) was obtained from the PDB database. In our study, the inhibitory activity of isoliquiritigenin towards HMG-CoA reductase showed a lower value of IC50 = 193.77 ±14.85 μg/ml. For a better understanding of biological activities and interactions, the molecular docking study was performed. The results of molecular docking revealed that isoliquiritigenin with a docking score of -6.740 has a strong binding affinity to HMG-COA reductase. Therefore, this compound could be considered as a potential inhibitor for the enzyme. Also, the activity of isoliquiritigenin against common human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47, was evaluated. The cells treated with isoliquiritigenin were assessed by MTT assay for 48 h as regards the cytotoxicity and anti-human pancreatic acinar cell tumor properties in normal (HUVEC) and human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47. The IC50 values of isoliquiritigenin were 262, 389, and 211 μg/ml against 266-6, TGP49, and TGP47 cell lines, respectively. The viability of the human pancreatic acinar cell tumor cell line decreased dose-dependently in the presence of isoliquiritigenin. After clinical study, isoliquiritigenin can be utilized as an efficient drug in the treatment of human pancreatic acinar cell tumor in humans.

Risk factors in autism spectrum disorder: A Tunisian case-control study

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition that causes disability in social interaction, communication, and restrictive and repetitive behaviors. Common environmental factors like prenatal, perinatal, and/or postnatal factors play a key role in ASD etiologies. Moreover, specific metabolic disorders can be associated with ASD. Subjects and methodsWe performed a retrospective case-control study in child psychiatry clinics, involving 51 children with ASD and 40 typical development controls (TDC). ResultsWe found a correlation between children being breastfed for less than 6 months, having fathers more than 40 years old at childbirth in ASD compared to TDC group. Our study also associated low blood cholesterol and low erythrocyte magnesium levels with increased risk for ASD. ConclusionFindings support the implication of total cholesterol (TC) and erythrocyte magnesium level in defining autism outcome.

In vitro antioxidant and cytochrome p450 inhibitory activity of dark chocolate mediated zinc oxide nanoparticles

Dark chocolate provides enormous health benefits owing to its enriched antioxidants, such as polyphenols and flavonoids, which can encounter free radicals in the body. These antioxidants can lower blood cholesterol, lowering your risk of heart attacks, cancer, high blood pressure, and stroke. This study was aimed to investigate both the free radical scavenging property and inhibitory property of dark chocolate mediated zinc oxide nanoparticles on activity of cytochrome P450 (CYP) isoform. The DC-ZnO was evaluated against free radicals formation using DPPH and ABTS free radical assays. Besides, the ZnO nanoparticles were also evaluated for CYP34A inhibitory activity. From the results it was demonstrated that there was a dose dependent increase in the inhibition of DPPH and ABTS free radicals and CYP3A4 inhibitory activity by the dark chocolate formulation mediated zinc oxide nanoparticles. The maximum inhibitory activity was observed at maximum concentration of 160µL. It may be thus concluded that the synthesized dark chocolate mediated zinc oxide nanoparticles possess potent antioxidant activity with significant inhibitory effect on Cytochrome P3A4 enzyme.