Hypoglycemic Effects of Polyphenol Complexes from Bilberry Leaves and Fruits Sorbed on Brown Buckwheat Flour -- Experimental Evaluation and Prospects of Use

The effects of plant polyphenols on carbohydrate and/or lipid metabolism disorders have wide experimental and clinical justification; however, their effects are limited due to low bioavailability. Thus, the development of technological approaches enhancing their effectiveness and stability is relevant.The aim of this work was to evaluatein vivothe effects of polyphenols from bilberry leaves and fruits, sorbed on the brown buckwheat flour, on C57Bl/6c mice with carbohydrate and lipid metabolism disorders. We assessed in vivothe effect of a food matrix (FM1: bilberry leaf polyphenols sorbed on brown buckwheat flour) on C57Bl/6c mice with induced carbohydrate and lipid metabolism disorders. The aim of the second experiment was to evaluate the effectiveness of prolonged prophylactic consumption of another food matrix (FM2: billberry fruit polyphenols, sorbed on brown buckwheat flour) by C57Bl/6c micewith induced carbohydrate and lipid metabolism disorders. Technological approaches were developed and pilot batches of the food matrices FM1 and FM2were obtained. According to the in vivo testing, a significant decrease in the glucose levels and normalization of glucose tolerance and insulin sensitivity were found in animals treated with FM1. When assessing the in vivo effects of FM2, the hypoglycemic effect of bilberry fruit polyphenols in the composition of the matrix was established. The results of these studies can be used to justify the testing of the developed matrices in a clinical setting and using them as functional food ingredients for preventative nutrition in cases of carbohydrate metabolism disorders. Keywords: polyphenols, food matrix, functional food ingredient, carbohydrate metabolism, lipid metabolism

PCSK9 Inhibitors in Clinical Practice: Experience of a Specialized Lipid Center

Aim. To characterize patients receiving PCSK9 inhibitors, and assess the efficiency of their treatment in a specialized lipid center.Material and methods. A retrospective analysis of the medical records of patients who visited the Lipid clinic of the National Medical Research Center for Therapy and Preventive Medicine (Moscow, Russia), receiving PCSK9 inhibitor and having lipid profile in dynamics, was carried out (n=77). Cardiovascular risk (CVR) and low-density lipoprotein cholesterol (LDL-C) target levels were evaluated in accordance with the Russian guidelines for the diagnostics and correction of dyslipidemias 2020.Results. Of 77 patients taking PCSK9 inhibitors (44.2% males, the median of age 56 [47; 66] years), the majority (64.0%) had a probable or definite familial hypercholesterolemia (FH). The proportion of other lipid metabolism disorders, pure hypercholesterolemia and combined hyperlipidemia was 21% and 15%. More than half of the patients (68.8%) had a very high CVR, mainly due to the presence of coronary heart disease (84.9%). The proportion of patients receiving PCSK9 inhibitors as monotherapy was 7.8%, in combination with high-intensity statin therapy – 33.8%, as part of triple lipid-lowering therapy (high-intensity statin, ezetimibe, PCSK9 inhibitors) – 50.6%. Addition of PCSK9 inhibitors to combined lipid-lowering therapy enabled to reduce the LDL-C level to 1.02 [0.62; 1.39] mmol/l with its total decrease from the baseline by 87.3%. While taking PCSK9 inhibitors, LDL-C <1.8 mmol/l and <1.4 mmol/l achieved at 78.3% and 57.7% FH patients with high and very high CVR, respectively. Among patients with other hyperlipidemias, 74.1% of patients with very high CVR was achieved the target LDL-C level <1.4 mmol/l.Conclusion: In a specialized lipid center, PCSK9 inhibitors are prescribed to patients with high or very high CVR, most of whom are FH patients. The effectiveness of the use of PCSK9 inhibitors in real-world practice is comparable to the results of clinical trials.

Unsolved Issues of Atherosclerosis Prevention and of Adequate Lipid-lowering Therapy in Patients with Acute Ischemic Cerebrovascular Accident

The existing system of medical care for patients with acute cerebrovascular accident of atherothrombotic genesis, namely lipid metabolism disorders, the modern evidence base for lipid-lowering therapy in this category of patients and the feasibility of interdisciplinary interaction of cardiologists and neurologists were discussed at a meeting of the expert council of cardiologists and neurologists in Moscow on 2021 July 7.

Kidney Damage Caused by Obesity and Its Feasible Treatment Drugs

The rapid growth of obesity worldwide has made it a major health problem, while the dramatic increase in the prevalence of obesity has had a significant impact on the magnitude of chronic kidney disease (CKD), especially in developing countries. A vast amount of researchers have reported a strong relationship between obesity and chronic kidney disease, and obesity can serve as an independent risk factor for kidney disease. The histological changes of kidneys in obesity-induced renal injury include glomerular or tubular hypertrophy, focal segmental glomerulosclerosis or bulbous sclerosis. Furthermore, inflammation, renal hemodynamic changes, insulin resistance and lipid metabolism disorders are all involved in the development and progression of obesity-induced nephropathy. However, there is no targeted treatment for obesity-related kidney disease. In this review, RAS inhibitors, SGLT2 inhibitors and melatonin would be presented to treat obesity-induced kidney injury. Furthermore, we concluded that melatonin can protect the kidney damage caused by obesity by inhibiting inflammation and oxidative stress, revealing its therapeutic potential.

Nonmedical correction of lipid metabolism disorders in patients with chronic cerebral ischemia

The authors evaluated the effectiveness of the isolated use of iodine-bromine baths and ozone therapy, as well as their complex application in the correction of lipid metabolism disorders in chronic cerebral ischemia. Statistical analysis of biochemical parameters after the treatment made it possible to come to the conclusion about the sufficient effectiveness and feasibility of using the proposed methods.

Physical Activity and Diet Quality: Effects on Cardiovascular Morbidity in Women with Turner Syndrome—Results from an Online Patient Survey

Turner syndrome (TS) is a rare chromosomal disease with increased cardiovascular morbidity and mortality. The aim of this study was to investigate the influence of physical activity and diet quality on cardiovascular morbidity in German TS women. An anonymous online questionnaire was established. The questionnaire was based on the 2020 WHO recommendations on physical activity and sedentary behaviour and included the 14-Item Mediterranean Diet Assessment Tool. In addition, TS patients were asked about existing cardiovascular conditions. In total, 83 TS women were included in the final analysis. The achievement of <600 Metabolic Equivalent-minutes per week for recreational activities was significantly associated with the presence of arterial hypertension (p = 0.006). High adherence to the Mediterranean diet was achieved by only 20.5% of TS subjects and tended to be inversely associated with the presence of lipid metabolism disorders (p = 0.063). Only 37.3% of TS participants received nutritional counselling. Given the increased cardiovascular risk, specific counselling for lifestyle optimisation may play an important role in the management of TS. Further studies are required to evaluate the effects of regular aerobic physical training and different nutritional programs on cardiovascular morbidity in TS.

Hyperuricemia induces lipid disturbances by upregulating the CXCL-13 pathway

The molecular mechanism underlying hyperuricemia-induced lipid metabolism disorders is not clear. The purpose of the current study was to investigate the mechanism of lipid disturbances in a hyperuricemia mice model. RNAseq showed that differentially expressed genes (DEGs) in the fatty acid synthesis signaling pathway were mainly enriched, and CXCL-13 was significantly enriched in protein-protein interaction networks. Western blotting, Q-PCR, and immunofluorescence results further showed that hyperuricemia upregulated CXCL-13 and disturbed lipid metabolism in vivo and in vitro. Furthermore, CXCL-13 alone also promoted the accumulation of lipid droplets and upregulated the expression of FAS and SREBP1, blocking AMPK signaling and activating the PKC and P38 signaling pathways. Silencing CXCL-13 reversed uric-acid-induced lipid droplet accumulation, which further downregulated FAS and SREBP1 expression, inhibited the p38 and PKC signaling, and activated AMPK signaling. In conclusion, hyperuricemia induces lipid metabolism disorders via the CXCL-13 pathway, making CXCL-13 a key regulatory factor linking hyperuricemia and lipid metabolism disorders. These results may provide novel insights for the treatment of hyperuricemia.

Hepatic Lipid Metabolism Disorder and Atherosclerosis

: Lipid metabolism disorder plays a fundamental role in the pathogenesis of atherosclerosis. As the largest metabolic organ of the human body, liver has a key role in lipid metabolism by influencing fat production, fat decomposition, and the intake and secretion of serum lipoproteins. Numerous clinical and experimental studies have indicated that the dysfunction of hepatic lipid metabolism is closely tied to the onset of atherosclerosis. However, the identity and functional role of hepatic lipid metabolism responsible for these associations remain unknown. This review presented that cholesterol synthesis, cholesterol transport, and the metabolism of triglyceride, lipoproteins, and fatty acids are all associated with hepatic lipid metabolism and atherosclerosis. Moreover, we also discussed the roles of gut microbiota, inflammatory response, and oxidative stress in the pathological association between hepatic lipid metabolism and atherosclerosis. These significant evidences support strongly that hepatic lipid metabolism disorders may increase the risk of atherosclerosis.

Gene polymorphisms associated with lipid metabolism disorders in young adults with risk of ­sudden cardiac death

Aim. To study the frequency of polymorphisms in genes associated with lipid metabolism disorders in young people with risk of sudden cardiac death, to identify the relationships between gene polymorphisms and risk factors of sudden cardiac death, and to develop mathematical models to identify the probability of carrying mutations in these genes. Methods. The study included 436 young people (mean age 19.81.6 years). A standard examination and survey by questionnaire specially developed by us were conducted to identify an increased risk of sudden cardiac death. 59 individuals with a risk of sudden cardiac death were selected. The control group was 65 people, which was comparable to the study group. A blood test was performed to determine lipid profile and polymorphisms: Leu28Pro (rs 429358) in gene APOE, C3238G (rs 5128) in gene APOC3, Gln192Arg (rs 662) in gene PON1, Ser447Ter (rs 328) in gene LPL, G250A (rs 1800588) in gene LIPC. Statistical analysis was performed using the statistical package SPSS 17.0 and Statistica 6.0. The parametric KruskalWallis test, the MannWhitney U-test, the Pearsons chi-squared test, the Spearman rank correlation coefficient, and logistic regression analysis were used. Results. We revealed a high frequency of Gln192Arg (rs 662) polymorphism in the PON1 gene in the group of individuals at risk of sudden cardiac death and its correlation with the deaths in relatives under age 50 years. Mathematical models for predicting the presence of polymorphisms in genes associated with lipid metabolism disorders have been developed. Among the developed mathematical models, the models for identifying carriers of the minor allele of Gln192Arg polymorphism in the PON1 gene, Ser447Ter in the LPL gene, and 250 GA in the LIPC gene had the highest sensitivity, specificity, and accuracy. Conclusion. In persons at risk for sudden cardiac death, it is advisable to conduct a screening for mutations in genes associated with lipid metabolism disorders, especially in Gln192Arg polymorphism in gene PON1.

The Possible Role of Herpesviruses in the Pathogenesis of Coronary Atherosclerosis

Cardiovascular diseases are still the dominant cause of death worldwide. Coronary artery disease (CAD) is the most common type of heart disease and the leading cause of death for both men and women. Coronary atherosclerosis underlies multiple clinical manifestations ranging from asymptomatic to stable angina, acute coronary syndrome, MI, heart failure, and sudden cardiac death. The prerequisites for a closer study of the pathogenesis of the atherosclerotic process were the development of atherosclerotic vascular lesions at a younger age and the rapid progression of the process. Currently, it is generally accepted that CAD is a multifactorial disease. Attention is drawn to hereditary disorders of the receptor apparatus, endothelial dysfunction, and lipid metabolism disorders. In addition, latent viral infections are one of the etiopathogenetic factors in the development of atherosclerosis. A number of scientific studies have confirmed the relationship between infectious agents and the development of atherosclerotic vascular lesions. The viral etiology of the development and progression of atherosclerosis is the subject of debate among scientists around the world.