Hypolipidemic Research Articles

Untargeted Lipidomic Profiling Reveals Lysophosphatidylcholine and Ceramide as Atherosclerotic Risk Factors in apolipoprotein E Knockout Mice.

Despite the availability and use of numerous cholesterol-lowering drugs, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality globally. Many researchers have focused their effort on identifying modified lipoproteins. However, lipid moieties such as lysophosphatidylcholine (LPC) and ceramide (CER) contribute to atherogenic events. LPC and CER both cause endothelial mitochondrial dysfunction, leading to fatty acid and triglyceride (TG) accumulation. In addition, they cause immune cells to differentiate into proinflammatory phenotypes. To uncover alternative therapeutic approaches other than cholesterol- and TG-lowering medications, we conducted untargeted lipidomic investigations to assess the alteration of lipid profiles in apolipoprotein E knockout (apoE-/-) mouse model, with or without feeding a high-fat diet (HFD). Results indicated that, in addition to hypercholesterolemia and hyperlipidemia, LPC levels were two to four times higher in apoE-/- mice compared to wild-type mice in C57BL/6 background, regardless of whether they were 8 or 16 weeks old. Sphingomyelin (SM) and CER were elevated three- to five-fold in apoE-/- mice both at the basal level and after 16 weeks when compared to wild-type mice. After HFD treatment, the difference in CER levels elevated more than ten-fold. Considering the atherogenic properties of LPC and CER, they may also contribute to the early onset of atherosclerosis in apoE-/- mice. In summary, the HFD-fed apoE-/- mouse shows elevated LPC and CER contents and is a suitable model for developing LPC- and CER-lowering therapies.

Lovastatin inhibits erythroleukemia progression through KLF2-mediated suppression of MAPK/ERK signaling

BackgroundLovastatin, an HMG-CoA inhibitor and an effective cholesterol lowering drug, exhibits anti-neoplastic activity towards several types of cancer, although the underlying mechanism is still not fully understood. Herein, we investigated mechanism of growth inhibition of leukemic cells by lovastatin.MethodsRNAseq analysis was used to explore the effect of lovastatin on gene expression in leukemic cells. An animal model of leukemia was used to test the effect of this statin in vivo. FAM83A and DDIT4 expression was knocked-downed in leukemia cells via lentivirus-shRNA. Western blotting, RT-qPCR, cell cycle analysis and apoptosis assays were used to determine the effect of lovastatin-induced growth suppression in leukemic cells in vitro.ResultsLovastatin treatment strongly inhibited cancer progression in a mouse model of erythroleukemia induced by Friend virus. In tissue culture, lovastatin inhibited cell proliferation through induction of G1 phase cell cycle arrest and apoptosis. Interestingly, lovastatin induced most known genes associated with cholesterol biosynthesis in leukemic cells. Moreover, it suppressed ERK1/2 phosphorylation by downregulating FAM83A and DDIT4, two mediators of MAP-Kinase signaling. RNAseq analysis of lovastatin treated leukemic cells revealed a strong induction of the tumor suppressor gene KLF2. Accordingly, lentivirus-mediated knockdown of KLF2 antagonized leukemia cell suppression induced by lovastatin, associated with higher ERK1/2 phosphorylation compared to control. We further show that KLF2 induction by lovastatin is responsible for lower expression of the FAM83A and DDIT4 oncogenes, involved in the activation of ERK1/2. KLF2 activation by lovastatin also activated a subset of cholesterol biosynthesis genes that may further contribute to leukemia suppression.ConclusionsThese results implicate KLF2-mediated FAM83A/DDIT4/MAPK suppression and activation of cholesterol biosynthesis as the mechanism of leukemia cell growth inhibition by lovastatin.

The changing landscape of drug clinical trials on cardiometabolic diseases in China, 2009–2021

BackgroundCardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009–2021.MethodsThe detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution.ResultsA total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution.ConclusionsGreat progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials.

Primary glomerular disease

This is a review of the clinical features, pathogenesis, investigation and management of glomerulonephritis (GN). GN can occur as a primary isolated renal disease, as a manifestation of systemic diseases such as vasculitis or lupus, or secondary to drugs, infections or tumours. It is an important cause of morbidity and mortality and a potentially preventable cause of end-stage renal disease; early diagnosis is vital to allow timely referral to specialist units where renal biopsy can be performed. Proteinuria and/or haematuria are typical findings. Pathogenesis involves immune cells and inflammatory mediators, with intrinsic glomerular cells, especially podocytes, also being important in glomerular injury and the responses to it. I present brief outlines of schemes for appropriate investigations when GN is suspected, and guidelines for referral strategies to investigate proteinuria and haematuria, and manage common forms of GN. When nephrotic syndrome (NS) is present, it can lead to major morbidity and potential mortality even if excretory renal function is well preserved. NS should be managed, irrespective of the cause, with diuretics, antiproteinuric agents, cholesterol-lowering agents and sometimes anticoagulants. Treatment with corticosteroids, with or without other immunosuppressive agents, is effective in many forms of GN, but adverse effects are problematic. More selective forms of immunotherapy are increasingly used as understanding of the pathogenesis of GN improves but there is a continuing need for better collaboration on clinical trials so that the evidence base can be improved.

Dietary cholesterol in alcohol-associated liver disease.

There is an increasing prevalence of alcohol-associated liver disease (ALD) worldwide. In addition to excessive alcohol consumption, other nutritional factors have been shown to affect the initiation and progression of ALD. The emerging role of cholesterol in exacerbating ALD has been reported recently and the underlying mechanisms are discussed. In addition, the interplay between dietary cholesterol and alcohol on cholesterol metabolism is reviewed. Furthermore, we highlight the therapeutic potential of cholesterol-lowering drugs in managing the onset and severity of ALD. Finally, we suggest the future mechanistic investigation of the effect of cholesterol on insulin resistance and intestinal inflammation in the exacerbation of alcohol-induced cellular and systemic dysfunction.

Exploring the anti-inflammatory activities, mechanism of action and prospective drug delivery systems of tocotrienol to target neurodegenerative diseases.

A major cause of death in the elderly worldwide is attributed to neurodegenerative diseases, such as AD (Alzheimer's disease), PD (Parkinson's disease), ALS (Amyotrophic lateral sclerosis), FRDA (Friedreich's ataxia), VaD (Vascular dementia) etc. These can be caused due to multiple factors such as genetic, physiological problems like stroke or tumor, or even external causes like viruses, toxins, or chemicals. T3s (tocotrienols) exhibit various bioactive properties where it acts as an antioxidant, anti-inflammatory, anti-tumorigenic, and cholesterol lowering agent. Since T3 interferes with and influences several anti-inflammatory mechanisms, it aids in combating inflammatory responses that lead to disease progression. T3s are found to have a profound neuroprotective ability, however, due to their poor oral bioavailability, their full potential could not be exploited. Hence there is a need to explore other drug delivery techniques, especially focusing on aspects of nanotechnology. In this review paper we explore the anti-inflammatory mechanisms of T3 to apply it in the treatment of neurodegenerative diseases and also discusses the possibilities of nano methods of administering tocotrienols to target neurodegenerative diseases.

Statins enhance the efficacy of HER2-targeting radioligand therapy in drug-resistant gastric cancers

Human epidermal growth factor receptor2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous discoveries that statins, a class of cholesterol-lowering drugs, can enhance the cell surface-bound HER2 to achieve effective drug delivery in tumors, we proposed that the combination of statins and [177Lu]Lu-trastuzumab-based RLT can enhance the therapeutic efficacy of HER2-targeted RLT in drug-resistant gastric cancers. We demonstrate that lovastatin elevates cell surface HER2 levels and increases the tumor-absorbed radiation dose of [177Lu]Lu-DOTA-trastuzumab. Furthermore, lovastatin-modulated [177Lu]Lu-DOTA-trastuzumab RLT durably inhibits tumor growth and prolongs overall survival in mice bearing NCI-N87 gastric tumors and HER2-positive patient-derived xenografts (PDXs) of known clinical resistance to trastuzumab therapy. Statins also exhibit a radioprotective effect, reducing radiotoxicity in a mice cohort given the combination of statins and [177Lu]Lu-DOTA-trastuzumab. Since statins are commonly prescribed to patients, our results strongly support the feasibility of clinical studies that combine lovastatin with HER2-targeted RLT in HER2-postive patients and trastuzumab-resistant HER2-positive patients.

Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma.

Cholesterol plays an important role in cancer progression, as it is utilized in membrane biogenesis and cell signaling. Cholesterol-lowering drugs have exhibited tumor-suppressive effects in oral squamous cell carcinoma (OSCC), suggesting that cholesterol is also essential in OSCC pathogenesis. However, the direct effects of cholesterol on OSCC cells remain unclear. Here, we investigated the role of cholesterol in OSCC with respect to caveolin-1 (CAV1), a cholesterol-binding protein involved in intracellular cholesterol transport. Cholesterol levels in OSCC cell lines were depleted using methyl-β-cyclodextrin and increased using the methyl-β-cyclodextrin-cholesterol complex. Functional analysis was performed using timelapse imaging, and CAV1 expression in cholesterol-manipulated cells was investigated using immunofluorescence and immunoblotting assays. CAV1 immunohistochemistry was performed on surgical OSCC samples. We observed that cholesterol addition induced polarized cell morphology, along with CAV1 localization at the trailing edge, and promoted cell migration. Moreover, CAV1 was upregulated in the lipid rafts and formed aggregates in the plasma membrane in cholesterol-added cells. High membranous CAV1 expression in tissue specimens was associated with OSCC recurrence. Therefore, cholesterol promotes the migration of OSCC cells by regulating cell polarity and CAV1 localization to the lipid raft. Furthermore, membranous CAV1 expression is a potential prognostic marker for OSCC patients.

Altered Functional State and Medicinal Therapeutics

Coronary Artery Disease is caused by plaque buildup in the walls of the arteries that supply blood to the heart (called coronary arteries) and other parts of the body. Plaque is made up of deposits of cholesterol and other substances in the artery. Plaque buildup causes the inside of the arteries to narrow over time, which could partially or totally block the blood flow. This process is called atherosclerosis. Coronary artery disease (CAD), when get worst, it is known as coronary artery syndrome (CAS). There are many allopathic medications which can stop, even at starting points of the disease (CAD). Hypolipidemic drugs like statins, fibrates, resins and niacin are well known agents used for prevention of CAD. There are ethnic-based medicinal herbs which can be used to treat or prevent CAD with narrow to moderate range of statistical significance. We compared Rosuvastatin 10 mg with Indian dates (Jujubes) as hypolipidemic agents. This research was conducted at Ghurki Trust Teaching Hospital, jalo park, Lahore, Pakistan. Duration of study was two months. Twenty to seventy years old 60 hyperlipidemic patients of both gender were included in research work with written consent. We divided these patients in two equal groups. Group-I was advised to take Tablet Rosuvastatin 10 mg, twice daily for two months. Group-II was advised to take 500 grams Indian dates for two months. Their baseline parameters like LDL-cholesterol, HDL-cholesterol, systolic/diastolic blood pressure was determined in the hospital laboratory. Separate file was maintained for their name, age, sex, occupation, and address. After two months therapy we compiled data related to tested parameters. Paired t-test was applied to compare changes in all parameters. Their mean values with ± SD before and after treatment were compared and analyzed statistically. It was observed that Rosuvastatin significantly decreased systolic/diastolic blood pressure, LDL-cholesterol, and increased HDL-cholesterol in 27 hyperlipidemic/hypertensive patients. Indian dates used in 30 hyperlipidemic patients significantly decreased systolic blood pressure, and LDL-cholesterol, but insignificant changes were seen in diastolic blood pressure, and HDL-cholesterol. We concluded from the research work that Rosuvastatin is potent hypolipidemic and hypotensive medicine as compared to indian dates.

Statin protects men but not women with HIV against loss of muscle mass, strength, and physical function: a pilot study

Statins are cholesterol-lowering drugs commonly used among people with HIV, associated with an increased risk of myopathies. Considering that cardiovascular disease, statin therapy, and sarcopenia are independently prevalent in people with HIV, clarity on the potential benefits or harms of statin therapy on muscle health is useful to provide insight into ways to maximize skeletal muscle health and minimize CVD risk in this population. We aimed to study the effects of statin therapy on strength, muscle mass, and physical function parameters in people with HIV. This was a pilot cross-sectional study. People with HIV on continuous statin therapy (n = 52) were paired 1:1 according to age (people with HIV 53.9 ± 8.2 and people with HIV on statins 53.9 ± 8.4 years), sex, body mass index (Body mass index, people with HIV 28.6 ± 5.3 and people with HIV on statins 28.8 ± 6.3 kg/m2), and race with people with HIV not using statin (n = 52). Participants were evaluated for muscle strength (i.e. handgrip strength), lean and fat body mass (using bioelectric impedance analysis), and physical function (i.e. Short Physical Performance Battery—SPPB). Isokinetic strength and appendicular lean mass (using dual-energy X-ray absorptiometry), more accurate strength and body composition measures, were determined in 38% of the participants. Overall, statin usage does not exacerbated loss of muscle strength (32.2 ± 11.5 vs. 30.3 ± 9.6 kg, p > 0.05) muscle mass (7.6 ± 1.8 vs. 7.7 ± 1.1 kg/m2, p > 0.05), and impaired physical performance (10.1 ± 1.8 vs. 9.7 ± 2.1 points, p > 0.05) of PLWH. When analyzed by sex, men living with HIV on statins usage presented higher appendicular muscle mass (28.4 ± 3.1 vs. 26.2 ± 4.9 kg, p < 0.05) handgrip strength (42.1 ± 8.8 vs. 37.1 ± 8.3 kg, p < 0.05) and physical function through SPPB score (10.9 ± 1.3 vs. 9.5 ± 2.1, p < 0.05) than men living with HIV not on statins treatment. The same protection was not observed in women. This data was demonstrated when muscle mass and strength were determined clinically (i.e. handgrip strength and electrical impedance) and when more precise laboratory measurements of muscle mass and strength were conducted (i.e. isokinetic strength and DXA scans). Statin does not exacerbate muscle wasting, strength loss, or muscle dysfunction among people with HIV. Indeed, statins may protect men, but not woman with HIV against HIV and antiretroviral therapy-induced loss of muscle mass and strength.

Virtual Screening of Novel 24-Dehydroxysterol Reductase (DHCR24) Inhibitors and the Biological Evaluation of Irbesartan in Cholesterol-Lowering Effect

Hyperlipidemia is a risk factor for the development of fatty liver and cardiovascular diseases such as atherosclerosis and coronary heart disease, and hence, cholesterol-lowering drugs are considered important and effective in preventing cardiovascular diseases. Thus, researchers in the field of new drug development are endeavoring to identify new types of cholesterol-lowering drugs. 3β-hydroxysterol-Δ(24)-reductase (DHCR24) catalyzes the conversion of desmosterol to cholesterol, which is the last step in the cholesterol biosynthesis pathway. We speculated that blocking the catalytic activity of DHCR24 could be a novel therapeutic strategy for treating hyperlipidemia. In the present study, by virtually screening the DrugBank database and performing molecular dynamics simulation analysis, we selected four potential DHCR24 inhibitor candidates: irbesartan, risperidone, tolvaptan, and conivaptan. All four candidates showed significant cholesterol-lowering activity in HepG2 cells. The experimental mouse model of hyperlipidemia demonstrated that all four candidates improved high blood lipid levels and fat vacuolation in the livers of mice fed with a high-fat diet. In addition, Western blot analysis results suggested that irbesartan reduced cholesterol levels by downregulating the expression of the low-density lipoprotein receptor. Finally, the immune complex activity assay confirmed the inhibitory effect of irbesartan on the enzymatic activity of DHCR24 with its half-maximal inhibitory concentration (IC50) value of 602 nM. Thus, to the best of our knowledge, this is the first study to report that blocking the enzymatic activity of DHCR24 via competitive inhibition is a potential strategy for developing new cholesterol-lowering drugs against hyperlipidemia or multiple cancers. Furthermore, considering that irbesartan is currently used to treat hypertension combined with type 2 diabetes, we believe that irbesartan should be a suitable choice for patients with both hypertension and hyperlipidemia.

Ezetimibe alleviates acetic acid-induced ulcerative colitis in rats: targeting the Akt/NF-κB/STAT3/CXCL10 signaling axis.

Ulcerative colitis (UC) is a relapsing inflammatory health state posing significant worldwide problems. Ezetimibe is a cholesterol-lowering drug having anti-inflammatory and pleiotropic properties. Twenty-four rats were classified into four groups (n = 6). Group (I) was considered negative control. Acetic acid (AA) was instilled intrarectally in groups (II-IV). Group (II) was considered UC-control. Groups (III and IV) were orally treated with Ezetimibe (5 and 10 mg/kg/day; 14 days). AA installation resulted in severe macroscopic colonic lesions associated with elevations in the relative colon weight, the wet weight/length ratio and oxidative stress markers in the colorectum tissues. UC-control rats showed significantly elevated colorectal tissue CXCL10 and STAT3 gene expression. Akt, phosphorylated Akt, phosphorylated STAT3, TNF-α, IL-6 and NF-κB were expressively upregulated in the UC-control group. AA installation also resulted in significant histopathological alterations in the colorectum tissues of UC-control rats along with increasing the colorectal tissues' immunohistochemical iNOS expression. Collectively, these data suggest activation of the Akt/NF-κB/STAT3/CXCL10 signaling axis. Ezetimibe treatment significantly ameliorated all the aforementioned parameters. This is the first study to elucidate the modulatory actions of Ezetimibe against oxidative stress and inflammation associated with AA-induced UC in rats. Ezetimibe treatment mitigates UC via downregulation of the Akt/NF-κB/STAT3/CXCL10 signaling axis.

Protective Effect of Hawthorn Fruit Extract against High Fructose-Induced Oxidative Stress and Endoplasmic Reticulum Stress in Pancreatic β-Cells

Hyperglycemia has deleterious effects on pancreatic β-cells, causing dysfunction and insulin resistance that lead to diabetes mellitus (DM). The possible causes of injury can be caused by glucose- or fructose-induced oxidative and endoplasmic reticulum (ER) stress. Hawthorn (Crataegus pinnatifida) fruit has been widely used as a hypolipidemic agent in traditional herbal medicine. The study aimed to investigate whether high fructose-induced pancreatic β-cell dysfunction could be reversed through amelioration of ER stress by the treatment of polyphenol-enriched extract (PEHE) from hawthorn fruit. The extract was partitioned using ethyl acetate as a solvent from crude water extract (WE) of hawthorn fruits, followed by column fractionation. The results showed that the contents of total polyphenols, flavonoids and triterpenoids in PEHE could be enhanced by 2.2-, 7.7- and 1.1-fold, respectively, in comparison to the original obtained WE from hawthorn fruit. In ER stress studies, a sharp increase in the inhibitory activity on the gene expression levels of GRP79, ATF6, IRE1α and CHOP involved in ER stress was evident when dosages of PEHE at 50-100 μg/mL were used against high-fructose (150 mM)-treated cells. HPLC-MS/MS analysis showed that polyphenols and flavonoids collectively accounted for 87.03% of the total content of PEHE.

γ–radiolytic degradation of rosuvastatin in the air–saturated aqueous solution

Widespread environmental occurrence and persistence of pharmaceuticals have attracted great concern due to their incomplete removal by conventional wastewater treatment technologies. The use of radiation technology has proven to be a good and successful alternative where highly reactive species lead to high degradation level of pharmaceuticals. Among the most commonly prescribed pharmaceuticals is rosuvastatin (ROSU), cholesterol-lowering agent, which has been detected as a contaminant in wastewater and natural waters. The aim of the present study was to investigate the γ-radiolytic degradation of ROSU in aqueous solutions under different conditions. The focus was given to the most applicable conditions, the degradation of ROSU in air, where dominant reactions of •OH radicals with ROSU are expected. Therefore, the reaction rate constant of ROSU with •OH radicals (2.15 ± 0.07 × 1010 M−1 s−1) was determined by laser flash photolysis. By combined γ-radiolysis and mass spectrometry study, the reaction mechanism of radiation degradation of ROSU was proposed and the radiolytic products were identified.

Inclisiran: present and future perspectives of a new effective LDL cholesterol-lowering agent.

To highlight critical aspects of inclisiran, from preclinical studies to current recommendations in clinical practice and future perspectives. Inclisiran use has been recently approved by regulatory agencies. The evidence of its efficacy and safety makes it a promising therapeutical tool for treating dyslipidemias. The link between LDL-cholesterol and atherosclerotic cardiovascular disease (ASCVD) is well established. Inclisiran, a small interfering RNA, has proven its safety and efficacy in reducing LDL-cholesterol, and FDA and EMA have recently approved its use. This review illustrates the development, structure, and mechanism of action of inclisiran and provides information regarding its efficacy, safety, and current recommendation in clinical practice. Moreover, it provides key information on the most recent/ongoing trials that will help us to implement the use of inclisiran in clinical practice.

Quality Assessment of Brands and Generic in Atorvastatin Tablets Available in Iraq-thi-Qar

Hypolipidemic agents have been shown to be helpful in the primary and secondary prevention of cardiovascular disease. Statins are frequently administered to treat hyperlipidemia. Although there are many statins on the market today, atorvastatin is the one that is most frequently recommended. The medications must meet the required physical qualities and contain the right quantity of active medicinal components. The primary goal of the study was to assess the value of several brands of atorvastatin calcium tablets sold in Iraq.Methods: In this study, the in vitro dissolving test, disintegration, friability, and hardness tests of the innovator product coded as (AT-1) and the generic brands (coded as AT-2) of atorvastatin tablets 20 mg available in Iraq were assessed. Drug analysis was done using a spectrophotometric technique. At a 240 nm wavelength, atorvastatin was found. The researched products released more than 90% of the atorvastatin in 30 minutes, per the findings of the dissolving testing. In under 30 minutes, the brands AT-1 and AT-2 showed a release of atorvastatin of over 95% and 86%, respectively. Our research revealed that the generic brand AT-2 and the innovator atorvastatin (AT-1) were of high pharmaceutical grade. In vitro dissolution, friability, disintegration, and hardness tests required by the pharmacopoeia were all passed by generic and innovator of atorvastatin tablets sold in the Iraqi market. Therefore, it was concluded that these generics might be utilized interchangeably by focusing on their in vitro release characteristics.

Metabolic switching of estrogen-related receptor alpha in breast cancer aggression.

Orphan nuclear receptor estrogen-related receptor alpha (ERRα) is an important regulator of energy metabolism, whereas its hyperactivation in breast cancer has been shown to regulate cell migration, proliferation, and tumour development. These findings suggest a fine balance in the status of ERRα in regulating metabolic homeostasis or promoting cancer progression. In this issue, Brindisi et al. have shown that ERRα is endogenously activated by cholesterol and caused breast cancer aggressiveness. This study also supports the anti-tumour mechanisms of cholesterol-lowering drugs such as statins.

Improved method of brewing peanut mouth with blending fruit drink of a high degree of readiness

The method of production of peanut paste with blended fruit and vegetable semi-finished products of high degree of readiness based on Jerusalem artichoke and cranberry obtained under conditions of low-temperature concentration has been improved. The production method is characterized by the process of concentration in a rotary-film apparatus at a temperature of 45...50 °C to a content of 28...30 % of dry substances within 1.75...2.00 minutes. The organoleptic evaluation of various recipe ratios of the selected raw materials revealed its optimal content in the semi-finished product (Jerusalem artichoke 65 %, cranberry 35 %), which has a uniform structure, a pleasant aroma of cranberry and Jerusalem artichoke, and its color is red-orange. The obtained fruit and vegetable semi-finished product of a high degree of readiness can be used as a base or additive in various food products of special purpose to increase their nutritional value and provide the products with a health-improving effect.&#x0D; For the production of health-prophylactic peanut paste, a technological manufacturing scheme is proposed with the addition of Jerusalem artichoke and cranberry fruit and vegetable paste to its composition, which will further increase the health-prophylactic properties of the finished product, eliminate the use of sugar and other synthetic stabilizers in comparison with classical technology. The organoleptic evaluation of the received samples of peanut paste with blended fruit and vegetable semi-finished product of a high degree of readiness revealed a rational amount of the semi-finished product at the level of 25 %, while the product has a structured, homogeneous consistency and a pleasant yellow-orange color. The obtained product can be recommended for therapeutic and preventive purposes, as a cholesterol-lowering and immunomodulating agent

Estimates of 10-year risk of cardiovascular death and adherence to cardiovascular risk factor management in Danish patients investigated for obstructive sleep apnea

ObjectiveObstructive sleep apnea (OSA) increases the risk of cardiovascular disease (CVD) in both morbidity and mortality. We used the risk chart of Systemic Coronary Risk Evaluation (SCORE) from European Society of Cardiology (ESC) to determine the 10-year risk of cardiovascular death, and adherence to cardiovascular risk factor management in Danish patients investigated for obstructive sleep apnea. Research design and methodsIn a prospective cohort study, 303 patients with mild, moderate and severe OSA were investigated for cardiovascular risk factors before initiating CPAP therapy. Primary outcome was estimates of 10-year risk of cardiovascular death assessed from the ESC risk chart SCORE based on sex, age, smoking status, systolic blood pressure and s-total cholesterol. Furthermore we analyzed treatment indication with statins in patients with mild (apnea-hypopnea index, AHI <15), moderate (AHI 15–29.9) and severe OSA (AHI ≥30). ResultsPatients with mild OSA predominately had low or moderate 10-year risk of CVD (low risk 55.4%, moderate risk 30.8%) while patients with moderate and severe OSA were more likely to have high or very high risk of 10-year CVD (p = 0.001). The large majority of included OSA patients had dyslipidemia, 235 (77.6%) and of those, only 27.4% were treated with cholesterol lowering drugs while additional 27.7% were eligible for oral statin supplement as risk-estimated by the ESC SCORE. In multiple regression analysis among statin naive patients, AHI was positively associated with statin eligibility when adjusted for age and sex. ConclusionPatients with moderate and severe OSA had an elevated 10-year risk of fatal CVD and were undertreated with CVD risk lowering agents such as statins.

Relationship between Cholesterol-Related Lipids and Severe Acute Pancreatitis: From Bench to Bedside

It is well known that hypercholesterolemia in the body has pro-inflammatory effects through the formation of inflammasomes and augmentation of TLR (Toll-like receptor) signaling, which gives rise to cardiovascular disease and neurodegenerative diseases. However, the interaction between cholesterol-related lipids and acute pancreatitis (AP) has not yet been summarized before. This hinders the consensus on the existence and clinical importance of cholesterol-associated AP. This review focuses on the possible interaction between AP and cholesterol-related lipids, which include total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) A1, from the bench to the bedside. With a higher serum level of total cholesterol, LDL-C is associated with the severity of AP, while the persistent inflammation of AP is allied with a decrease in serum levels of cholesterol-related lipids. Therefore, an interaction between cholesterol-related lipids and AP is postulated. Cholesterol-related lipids should be recommended as risk factors and early predictors for measuring the severity of AP. Cholesterol-lowering drugs may play a role in the treatment and prevention of AP with hypercholesterolemia.