Metabolic Disorders Research Articles

Quality of life as a reflection of metabolic indicators in patients undergoing programmed hemodialysis

Metabolic disorders associated with chronic kidney disease (CKD) can lead to a decrease in the quality of life of patients on hemodialysis. The aim of this study is to analyze the correlation between quality of life (QOL) in patients receiving treatment with PHD and clinical and laboratory indicators. Material and methods. 251 patients with stage 5 CKD were included in the study. There were 108 men and 143 women. The mean age was 54.4 ± 9.9 years. All participants completed a specific quality of life questionnaire KDQOL-SF. Results. The interviewed patients reported more concern about symptoms such as weakness, dizziness, and muscle pain (U = 765, p < 0.001), which was correlated with albumin levels (R = 0.5, p < 0.01) and calcium-phosphorus product levels (R = –0.48, p < 0.05). They also expressed concern about the inability to travel or follow a special diet (U = 553, p < 0.005), which correlated with heart rate levels (R = –0.51, P < 0.1) and serum potassium levels (R = –0.6, P < 0.1). Additionally, the burden of CKD correlated with triglycerides (R = 0.36, p = 0,01).Work capacity is associated with age (R = –0.54; p < 0.001), eKT/V (R = 0.47; p < 0.01). Indicators of cognitive function correlate with blood pressure (BP) (R = –0.51, p < 0,001) and pulse pressure (P = –0,55, p < 0,01). Sexual functions are associated with BP (R = –0,64, p < 0,05), calcium levels (R = 0,76, p > 0.80), iron (0,42, p = 0,90), transferrin saturation coefficient (0.5, p = 0.91). Sleep quality correlates with calcium-phosphate production (0.3, p > 0.15). The feeling of social support correlates with magnesium (0,3, P > 0,8), calcium (0.2, P > 0,1). Conclusions. Correlations between quality of life, blood pressure, albumin, and calcium phosphate metabolism, iron, were found.

Role of SIRPG gene in type 1 diabetes and lichen planus

Type 1 diabetes (T1D) is a form of diabetes caused by pancreatic β-cell destruction and absolute insulin deficiency. Lichen planus (LP) is an idiopathic inflammatory skin disease of unclear etiology. The role of SIRPG gene dysregulation in T1D and LP remains unclear. Mendelian randomization (MR) using matched samples was employed to study causal relationship between T1D and increased risk of LP. T1D-related single nucleotide polymorphism identification was conducted. Datasets GSE156035 for T1D and GSE52130 for LP were obtained from gene expression omnibus. Differentially expressed genes were identified, analyses included weighted gene co-expression network analysis, functional enrichment, gene set enrichment analysis, and protein–protein interaction network construction and analysis. Heatmaps of gene expression levels were generated. Comparative toxicogenomics database was used to identify diseases most relevant to core genes. Inverse variance weighted, MR-Egger, weighted median methods estimated genetic predisposition between T1D and LP, showing consistent positive correlations using both weighted median and inverse variance weighted methods. Horizontal pleiotropy analysis with MR-Egger intercept indicated no evidence of significant directional pleiotropy (P = .70645) for LP. There was no evidence of directional pleiotropy effects between T1D and LP. One hundred eighteen differentially expressed genes were identified. In biological processes, they were mainly enriched in apoptosis, inflammatory response, insulin receptor signaling pathway, glucose metabolism. In cellular components, enrichment was observed in mediator complex and replication fork. In molecular function, they were concentrated in leukotriene receptor activity and helicase activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment in metabolic pathways, PI3K-Akt signaling pathway, cell cycle, p53 signaling pathway, AGE-RAGE signaling pathway in diabetic complications. Weighted gene co-expression network analysis with a soft threshold power of 4. SIRPG showing high expression in both T1D and LP samples. There is a positive causal relationship between T1D and LP. Comparative toxicogenomics database analysis revealed associations of core genes with metabolic syndrome, lipid metabolism disorders, cardiovascular diseases, immune system diseases, peripheral neuropathic pain, and inflammation. SIRPG is highly expressed in both T1D and LP, providing a new insight into the pathogenesis of T1D and LP.

S1P regulates intervertebral disc aging by mediating endoplasmic reticulum-mitochondrial calcium ion homeostasis.

As the aging process progresses, age-related intervertebral disc degeneration (IVDD) is becoming an emerging public health issue. Site-1 protease (S1P) has recently been found to be associated with abnormal spinal development in patients with mutations and has multiple biological functions. Here, we discovered a reduction of S1P in degenerated and aging intervertebral discs, primarily regulated by DNA methylation. Furthermore, through drug treatment and siRNA-mediated S1P knockdown, nucleus pulposus cells were more prone to exhibit degenerative and aging phenotypes. Conditional KO of S1P in mice resulted in spinal developmental abnormalities and premature aging. Mechanistically, S1P deficiency impeded COP II-mediated transport vesicle formation, which leads to protein retention in the endoplasmic reticulum (ER) and subsequently ER distension. ER distension increased the contact between the ER and mitochondria, disrupting ER-to-mitochondria calcium flow and resulting in mitochondrial dysfunction and energy metabolism disturbance. Finally, using 2-APB to inhibit calcium ion channels and the senolytic drug dasatinib and quercetin (D + Q) partially rescued the aging and degenerative phenotypes caused by S1P deficiency. In conclusion, our findings suggest that S1P is a critical factor in causing IVDD in the process of aging and highlight the potential of targeting S1P as a therapeutic approach for age-related IVDD.

Oleocanthal and Oleacein from Privet Leaves: An Alternative Source for High-Value Extra Virgin Olive Oil Bioactives

Current research strongly suggests that phenolic compounds in extra virgin olive oil (EVOO) are potent preventive and therapeutic agents against metabolic diseases associated with inflammation and oxidative stress. Oleocanthal (OC) and oleacein (OA) are two of the most abundant and promising EVOO phenolics. To fully establish their health-promoting efficacy, additional animal studies and human clinical trials must be conducted, but the sourcing of both compounds at gram scale, reasonable cost, and ease of access remains a challenge. Here, we describe an extraction procedure to obtain OC and OA from the common privet (Ligustrum vulgare), a fast-growing, semi-evergreen shrub. We show that, compared to the olive tree, in addition to its broader geographical distribution, L. vulgare offers the benefit of yielding both OA and OC from its leaves. We also demonstrate the necessity of providing adapted enzymatic conditions during leaf treatment to optimize OC and OA concentrations in the final extracts.

Succinic Acid Improves the Metabolism of High-Fat Diet-Induced Mice and Promotes White Adipose Browning

Succinic acid plays a crucial role as an essential intermediate in the mitochondrial tricarboxylic acid cycle in mitochondria. In recent years, growing evidence has supported the the important role of succinic acid in fat metabolism. Therefore, we aimed to investigate the effects of succinic acid on adipose tissue metabolism and insulin sensitivity in high-fat diet (HFD)-induced obese mice and try to explore its potential mechanism. We found that the addition of succinic acid (40 mM) to drinking water inhibited the hypertrophy of inguinal white adipose tissue (iWAT) in HFD-induced mice. Furthermore, succinic acid supplementation enhanced insulin sensitivity and improved their glucose tolerance in obese mice. Interestingly, succinic acid supplementation improved lipid metabolism in HFD-fed mice, as shown by decreased serum levels of TG, TC, LDL-C, and increased HDL-C. In addition, succinic acid supplementation increased the expression of browning markers and mitochondria-related genes in iWAT. Further studies showed that the addition of succinic acid to drinking water promotes the browning of iWAT by activating the PI3K-AKT/MAPK signaling pathway. These results suggest that succinic acid has the potential to be used as an effective component for dietary intervention and may, therefore, play an important role in ameliorating and preventing obesity and associated metabolic diseases caused by HFD.

Relationship of different metabolic obesity phenotypes with reflux esophagitis: a propensity score matching analysis

BackgroundObesity is associated with an increased risk of reflux esophagitis (RE). Metabolic abnormalities have been implicated in the pathogenesis of RE. However, the role of metabolic status in the risk of RE among individuals with varying degrees of obesity remains unclear. Therefore, our study aimed to assess the association between metabolic obesity phenotypes and the risk of RE.MethodsThis study included a cohort of 24,368 participants aged 18 years and older who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital of Dalian Medical University during health checkups between January 1, 2008, and December 31, 2021. Among these participants, a total of 9,947 individuals were classified into four groups based on their obesity phenotype: metabolically healthy normal weight (MHNW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO). To account for potential confounding factors, multivariate logistic regression analysis was applied to examine the association between metabolic obesity phenotypes and the risk of RE, with stratification by sex and age.ResultsAmong all participants, the MUNW, MHO, and MUO groups demonstrated a higher risk of RE when compared to the MHNW group. After controlling for all confounding factors, the MUO group exhibited the highest risk, with an odds ratio (OR) of 3.723 (95% CI: 2.751–5.040) in males and 5.482 (95% CI: 4.080–7.367) in females. The prevalence of RE increased in proportion to the number of metabolic risk factors. Subgroup analyses, which accounted for all confounders, revealed that the MHO, MUNW, and MUO phenotypes were associated with an elevated risk of RE in individuals under 60 years old as well as those over 60 years old. Interestingly, a more comprehensive analysis indicated that obesity may have a greater effect on the risk of RE than metabolic disorders.ConclusionsBoth metabolic disorders and obesity were associated with an increased risk of RE. The effect of obesity on RE prevalence may be stronger than that of metabolic disorders, emphasizing the significance of obesity regardless of metabolic health status. Clinical interventions should address not only obesity but also metabolic disorders in order to reduce the risk of RE.

The cellular and molecular mechanisms mediating the protective effects of sodium-glucose linked transporter 2 inhibitors against metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a common, highly heterogeneous condition that affects about a quarter of the world's population, with no approved drug therapy. Current evidence from preclinical research and a number of small clinical trials indicates that SGLT2 inhibitors could also be effective for MAFLD. MAFLD is associated with a higher risk of chronic liver disease and multiple extrahepatic events, especially cardiovascular disease (CVD) and chronic kidney disease (CKD). MAFLD is considered a more appropriate terminology than NAFLD because it captures the complex bidirectional interplay between fatty liver and metabolic dysfunctions associated with disease progression, such as obesity and type 2 diabetes mellitus (T2DM). SGLT2 inhibitors are antidiabetic drugs that block glucose reabsorption in the kidney proximal tubule. In this article, we reviewed current clinical evidence supporting the potential use of SGLT2 inhibitors as a drug therapy for MAFLD and discussed the possible cellular and molecular mechanisms involved. We also reviewed the clinical benefits of SGLT2 inhibitors against MAFLD-related comorbidities, especially CVD, CKD and cardiovascular-kidney-metabolic syndrome (CKM). The broad beneficial effects of SGLT2 inhibitors support their use, likely in combination with other drugs, as a therapy for MAFLD.

Therapeutic Potential of Quercetin Analogous: Prospective and Advances

The purpose of the article is to investigate the therapeutic potential of quer-cetin and related compounds by elucidating their pharmacological characteristics and molecular mechanisms of action. The potential benefits of quercetin and its analogs for cardiovascular health, disorders of the brain, metabolic disorders, and more are discussed in the discussion part of this page. Concerns about their clinical efficacy due to issues with bioavailability and distribution are also discussed. This region of the paper emphasizes the importance of researchers and clinicians working together to maximize the incorporation of these chemicals into real-world therapeutic approaches. In conclusion, quercetin, along with related substances, shows great potential in a wide range of therapeutic settings. Potentially useful for the management of a wide variety of illnesses, their multiple methods of action include the regulation of pathways for cell signaling and interaction with different enzymes. However, additional clinical tri-als are needed to verify their efficacy and safety.

The GDF15 3′ UTR Polymorphism rs1054564 Is Associated with Diabetes and Subclinical Atherosclerosis

Growth differentiation factor 15 (GDF15) is a stress-response cytokine related to a wide variety of metabolic diseases. However, the impact of GDF15-specific genetic variants on the abovementioned conditions is poorly known. The aim of this study was to assess the impact of selected GDF15 single-nucleotide polymorphisms (SNPs) on metabolic disturbances and subclinical atherosclerosis. A cross-sectional study involving 153 participants of a metabolic patient-based cohort was performed. Three selected SNPs (rs888663, rs1054564 and rs1059369) in a locus on chromosome 19 including the GDF15 gene were genotyped by Polymerase Chain Reaction (PCR), and its relationship with the serum GDF15 levels, health status and clinical variables were analyzed. Of the three SNPs analyzed, only rs1054564 showed different distributions between the healthy volunteers and patients suffering lipid alterations and associated disorders. Accordingly, just the rs1054564 variant carriers showed a significant increase in GDF15 serum levels compared to the wild-type carriers. The group of variant carriers showed a higher frequency of individuals with diabetes, compared to the wild-type carrier group, without showing differences in other metabolic conditions. Additionally, the frequency of individuals with atherosclerotic carotid plaque was higher in the rs1054564 variant carriers than in the wild-type carriers. Logistic regression models identified that the presence of the rs1054564 variant carriers increase the likelihood for both diabetes and carotid plaque independently of confounding factors. Overall, the findings of this study identify the rs1054564 variant as a potential indicator for the likelihood of diabetes and subclinical atherosclerosis.

Health screening and its association with emergency department visits and related costs among home-dwelling older adults

Background The aim of this study was to evaluate the effectiveness of the health screening procedure for home-dwelling older adults in reducing emergency department visits and associated costs. Methods Data were derived from health screenings from 2020 to 2021 for 75-year-old home-dwelling residents of Western Finland. The study compared emergency department visits and associated costs between older adults who participated in the health screening (intervention group) and those who did not (non-intervention group). For each older adult, three non-intervention controls were matched according to age, sex, health screening year and wellbeing service county. Emergency department visits and International Classification of Diseases (ICD)-10 codes from one year before to two years after health screening were analyzed. Results In the non-intervention group, a 19% increase in emergency visit rates was seen (457–564 per 1000 person-years), while the intervention group showed a 67% decrease (165–23). Annual costs for the non-intervention group increased from 148 euros (€) to €183, a mean ratio increase of 1.24 per person-year (range 1.08–1.40). In contrast, the intervention group’s costs decreased from €53 to €8, a mean reduction ratio of 0.15 per person-year (range 0.10–0.71). The intervention group had lower frequency of visits for respiratory and circulatory diseases but higher for digestive and metabolic diseases, unlike the non-intervention group. Conclusions The implementation of the health screening is an effective strategy for reducing both the frequency of emergency department visits and associated costs in home-dwelling older adults in good condition.

Fecal microbiota transplantation for the treatment of intestinal and extra‐intestinal diseases: Mechanism basis, clinical application, and potential prospect

AbstractTo review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra‐intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra‐intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.

Seasonal differences of 25-hydroxyvitamin D concentrations in children and adolescents from Mexico City and Metropolitan Area

Introduction: Vitamin D deficiency is associated with bone metabolism and immune disorders. Radiation's seasonal variation affects vitamin D status more at the poles. In Mexico, near the equator, there have been reports of 10-20% vitamin D deficiency in children. There is no consensus on the definition of vitamin D deficiency, different organizations consider that a vitamin D level should be above 20 to 30 ng/ml. This study aimed to analyze vitamin D serum concentrations in children and adolescents from Mexico City and the Metropolitan Area (MA) during different seasons. Methods: Cross-sectional study in children and adolescents aged 5-20 years from Mexico City and Metropolitan Area, from autumn 2016 to winter 2017. Variables of interest such as anthropometric measurements, food consumption, and physical activity were analyzed. Results: A total of 816 children and adolescents were included. A high frequency of vitamin D deficiency was detected in 40.7% of the sample. The lowest vitamin D status occurred in winter 2016 and winter 2017. Conclusion: We found a higher frequency of vitamin D deficiency during winter in children and adolescents in Mexico City and MA. This risk persisted after adjusting for age, sex, BMI Z-score, milk consumption, physical activity, and screen time.

Comorbidity problems in patients with osteoporosis

BACKGROUND: Osteoporosis is a metabolic skeletal disease characterized by decreased bone mass, impaired microarchitecture of bone tissue and, as a consequence, fractures with minimal trauma. The social significance of osteoporosis is determined by its consequences — fractures of the vertebral bodies and bones of the peripheral skeleton, leading to high medical costs and causing a high level of disability, including disability and mortality. Osteoporosis is most often combined with cardiovascular diseases caused by atherosclerosis, which are widespread and are the leading cause of disability and mortality. A small number of studies have been devoted to the study of the features of clinical manifestations of cardiovascular diseases in the combination of coronary heart disease and osteoporosis. AIM: To identify the frequency and severity of comorbid diseases and their risk factors in postmenopausal osteoporosis. MATERIALS AND METHODS: A retrospective and prospective cohort study was conducted from 2013 to 2023. 8250 women with postmenopausal osteoporosis were examined and the data from the medical records of these patients who applied to the Osteoporosis Center of the North-Western State Medical University named after I.I. Mechnikov of the Ministry of Health of the Russian Federation from 2013 to 2020 were analyzed. At the prospective stage, two comparison groups of 100 patients with and without postmenopausal osteoporosis were formed from 500 patients with comorbid diseases (coronary heart disease, hypertension, type 2 diabetes, stroke, transient ischemic attack). Bone mineral density was assessed based on the Hologic Discoveri Wi dual-energy X-ray absorptiometry at 2 points in the lumbar spine (L1–L4) and the femoral neck. Along with traditional laboratory examination methods, bone metabolism markers (total calcium, phosphorus, vitamin D, urine analysis for deoxypyridinoline, C-terminal telopeptide of type 1 collagen, osteocalcin, alkaline phosphatase, parathyroid hormone) were assessed dynamically. In all the patients, along with a general clinical examination, an assessment of risk factors for cardiovascular disease and osteoporosis was performed. RESULTS: Body mass index was higher in the group of patients with osteoporosis — 28.4 (26.9–32.4) kg/m2 (p 0.001), versus 27.64 (25.8–30.0) kg/m2 (p 0.05). Bone mineral density in the group of patients with osteoporosis was statistically lower than in the group without osteoporosis. In the group of patients with osteoporosis, the risk of fractures was high and amounted to 37 (95% confidence interval 15.0–38.50) %, p 0.001), versus in the control group 9.55 (95% confidence interval 7.67–15.0) % (p 0.001) according to the FRAX questionnaire for the Russian Federation. In the group of patients with osteoporosis, the Charlson index values were 5.1 (95% confidence interval 4.7–5.6) points. As a result of the correlation analysis, a reliable positive relationship was revealed between low bone mineral density L1–L4 and hip with bone metabolism: alkaline phosphatase, C-terminal telopeptide of type 1 collagen, vitamin D, osteocalcin, urinary deoxypyridinoline. We found a negative relationship between bone mineral density and the Charlson index, absolute ten-year risk of hip fracture and the duration of early menopause, and the level of hypertension. To assess the dependence of QRISK3-2018 on osteoporosis risk factors in the group of patients with osteoporosis, multiple linear regression was performed. This model was characterized by a statistically significant correlation between the factors and the dependent variable of high tightness. The coefficient of determination was 0.608, indicating a 60.8% contribution of the factors taken into account in the model to the variance of QRISK3-2018. CONCLUSIONS: In women with postmenopausal osteoporosis, comorbid pathology is more common, aggravating the course of the disease. Knowledge of the prevalence of concomitant pathology and joint risk factors will make it possible to simultaneously form groups at increased risk of development, which will ensure prevention of both diseases with the same non-medical means and drugs.

Based on Serum Pharmacochemistry and Metabolomics Studied the Pharmacodynamic Material Basis and Mechanism of Rubi Fructus (Fupenzi) in Improving the Symptom of Kidney-Yang Deficiency.

Rubi fructus (Fupenzi) is the immature fruit of East China Rubi fructus, which is widely used in medicine, food, health food and other fields. Since ancient times, Fupenzi has been considered to be an important medicine for tonifying the kidney in terms of nourishing the liver and kidney, fixing essence and reducing urine, but its effective components and mechanism are not clear. In this paper, the effective components of Rubi fructus were analyzed by detecting the components of Fupenzi in vivo and in vitro. Adenine was used to replicate the model of kidney yang deficiency, and organ index, biochemical index and histopathology were used to evaluate the effect of different doses of Fupenzi on tonifying kidney yang. Metabonomics technique was used to analyze the metabolic regulation mechanism of Fupenzi in improving kidney yang deficiency syndrome. The results showed that 61 chemical constituents of Fupenzi were identified in vitro, including 18 flavonoids, 19 organic acids, 5 coumarins, 8 terpenoids, 7 amino acids and 4 other components. A total of 51 chemical components were identified, including 30 prototype components and 21 metabolic components, which may be the effective components of Fupenzi. The results of pharmacodynamics showed that compared with the model group, the renal index, testicular index and epididymal index of rats in each Fupenzi group were significantly improved (p<0.01), cAMP significantly increased (p<0.05), cGMP decreased (p<0.05) and cAMP/cGMP ratio increased significantly (p<0.05). The content of ACTH in low dose group increased significantly (p<0.05), while the content of ACTH in middle and high dose groups increased, but there was no significant difference. The results of HE staining showed that compared with the model group, the kidney, testis and epididymis of rats in each treatment group were significantly improved. In general, these changes may be mainly through primary bile acid biosynthesis, linoleic acid metabolism, steroid hormone biosynthesis, β-alanine metabolism, glutathione metabolism, porphyrin and chlorophyll metabolism, unsaturated fatty acid biosynthesis, arachidonic acid metabolism, arginine and proline metabolism and other metabolic pathways to improve adenine-induced metabolic disorders in rats with kidney-yang deficiency syndrome.

Electrochemical behavior and L-tyrosine sensing properties of nanostructured Cr, Sn and La-doped α-Fe2O3 interfaces

L-tyrosine (Tyr) is a promising biomarker for the diagnosis and monitoring of metabolic disorders and neurodegenerative diseases. This study reports on the electrochemical properties of α-Fe2O3 nanostructures doped with Cr, Sn and La, referred to as CrFeOx, SnFeOx and LaFeOx, respectively, and their application in the enzyme-free electrochemical Tyr sensors. These disposable sensors offer accurate Tyr concentration analysis at room temperature, addressing the limitations of current point-of-care diagnostic methods. The CrFeOx, SnFeOx, and LaFeOx nanostructures serve as selective agents for binding and recognizing Tyr, deposited onto disposable graphite pencil electrodes to form the electrochemical interface. The interfacial resistance, charge-transfer kinetics, mechanism, and reversibility are studied via extensive electrochemical measurements employing electro¬chemical impedance spectroscopy and cyclic voltammetry. Furthermore, differen¬tial pulse voltammetry demonstrates excellent Tyr sensing performance in the concen¬tration range of 0 to 80 μM with 2.65 µA µM-1 cm-2 sensitivity and 360 nM thres¬hold detection limit for the best-performing CrFeOx sensors. Hence, these α-Fe2O3-based sensor systems are practical and efficient for selective Tyr detection, offering potential advancements in personalized healthcare and early disease diagnosis.

Genetic Polymorphisms in Obesity: How Variants in Lipid Metabolism Genes Contribute to Hyperlipidemia

Obesity is a complex metabolic disorder influenced by both environmental and genetic factors. Among the genetic contributors, polymorphisms in lipid metabolism genes play a significant role in regulating lipid profiles and promoting hyperlipidemia. This review aims to explore the impact of genetic variants on lipid metabolism in individuals with obesity, focusing on genes such as APOE, LPL, FTO, PCSK9, CETP, and FABP. These polymorphisms alter lipid processing, transportation, and storage, leading to aberrant lipid levels, which contribute to hyperlipidemia and subsequent cardiometabolic complications. We will also discuss the gene-environment interactions that modulate these genetic effects and review potential therapeutic interventions targeting lipid metabolism to manage hyperlipidemia in obese individuals. Keywords: Genetic polymorphisms, obesity, lipid metabolism, hyperlipidemia, gene-environment interactions, cardiometabolic disease

MRNA therapy effective treatment of rare hereditary diseases

mRNA therapy, or mRNA-based drugs that have emerged thanks to vaccines against SARS-CoV-2, have successfully passed preclinical tests and are currently at various stages of clinical trials in the treatment of many diseases, including rare metabolic disorders. In the case of rare genetic metabolic diseases, the concept of mRNA therapy can be considered as an alternative to protein replacement therapy, where exogenous mRNA leads to the production of a fully active protein instead of a non-functional one, and also delivers it to the desired cellular compartment, such as mitochondria or the cell membrane. Preclinical studies on animal models of some rare genetic diseases have fully confrmed the validity of this concept. In this mini-review, we examine and discuss the mentioned preclinical studies on efficacy and safety in several animal models. For all the diseases considered, mRNA therapy restored functional protein to therapeutically significant levels in target organs, led to stable and reproducible results after each dose of mRNA, and was well tolerated, as confirmed by functional liver tests evaluated in animal models, including non-human primates. These data convincingly confirm the potential of clinical development of mRNA therapy for the treatment of various rare metabolic disorders.

EFFECT OF EXERCISE ON BURST FREQUENCY A MARKER OF SYMPATHETIC ACTIVITY IN HYPERTENSIVE INDIVIDUALS: A SYSTEMATIC REVIEW.

Background: Burst frequency is a factor that is used to know the relationship between sympathetic activity and blood pressure in individuals with hypertension. Various forms of exercise reduce the burst frequency among individuals with hypertension. This systematic review provides suggestion of exercise prescription for reducing blood pressure. Objective: To determine the effects of exercise training and its regulatory mechanisms on burst frequency (BF) a marker of muscle sympathetic nerve activity (MSNA) in hypertensive individuals. Methods: A systematic literature search of electronic databases such as PubMed, Web of Science and Scopus was conducted from inception to July 2024 included randomized controlled trials (RCTs), non-randomized experimental studies (non-RCTs) or pre-post experimental trials on hypertensive patients without associated metabolic disorders, with or without pharmacological treatment, aged between 18 and 70 years, both genders. Patients underwent at least 4 weeks of aerobic, resistance, or breathing exercises with BF as an outcome measure were included. The Revised Cochrane Risk of Bias tool (RoB 2) and Risk of Bias in Non-randomized Studies of Interventions tool (ROBINS-I) was used to evaluate the risk of bias. Results: Five trials were included. Four studies demonstrated a significant reduction in BF among exercise-trained hypertensive individuals, while one study reported no change in BF. Overall, two studies had "some concerns" about performance and attrition bias, one had "high RoB" for selection bias, one had “moderate RoB” due to expected confounding, and one had “serious RoB” due to uncontrolled confounding factors. Conclusion: These findings suggests that HIIT significantly reduces BF, while aerobic and breathing exercises offers lesser benefits, further research should focus on training dosages. Implications: It provides evidence to utilize tailored exercise programme that may reduce sympathetic overactivity in hypertensive patients for better blood pressure control and reduce cardiovascular risk.

Features of reproductive function and IVF programs in patients with overweight and obesity

Obesity is a chronic multifactorial heterogeneous disease characterized by high prevalence, progressive increase in morbidity, high cardiometabolic risk. The prevalence of obesity is increasing from year to year and does not tend to decrease. Up to 60% of women of reproductive age are overweight, and a quarter of them are obese. In addition to cardiovascular pathology, type 2 diabetes, gastrointestinal diseases, oncological processes, obesity can affect the reproductive function of women, reduce fertility and be an independent cause of infertility, as well as reduce the effectiveness of assisted reproductive technology programs. This paper analyzes studies on the problem of reproductive system disorders, the effectiveness and safety of assisted reproductive technology programs in patients with overweight / obesity. The review includes data from foreign and domestic articles in the Pubmed, Elsevier, Cochrane Library, e_library databases published over the past 10 years. As a result of the analyzed publications, it was concluded that the implementation of IVF programs in patients with overweight/obesity presents certain difficulties at each stage of the program: the duration and cost of ovarian stimulation increases, the number and quality of the obtained oocytes and embryos decreases, the displacement of the “implantation window” is more often noted, decreased endometrial receptivity, which together causes a decrease in the pregnancy rate (PR) in this category of patients. It should be noted that in women with visceroabdominal obesity, with more pronounced metabolic abnormalities – dyslipidemia, carbohydrate metabolism disorders, reproductive disorders are expressed to a greater extent than in patients with a more favorable femoral phenotype type of obesity, which requires an individual approach to the treatment of infertility using IVF methods depending on the clinical and etiopathogenetic category of patients.

Ferroptosis as a Therapeutic Target in Neurodegenerative Diseases: Exploring the Mechanisms and Potential of Treating Alzheimer's Disease and Parkinson's Disease

Amidst the rising global burden of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, there is an urgent need for novel therapeutic strategies to combat these debilitating conditions. These diseases are characterized by progressive neural dysfunction leading to cognitive impairments, for which current therapeutic strategies remain palliative at best. Recently, the discovery of ferroptosis, a novel cell death mode that is different from apoptosis and autophagy, has opened new avenues in the field of cognitive research. With in-depth research on ferroptosis, the clinical significance of iron homeostasis disorders and lipid peroxidation in the occurrence, development, and treatment of neurodegenerative diseases are gradually becoming apparent. This study aims to elucidate the roles of ferroptosis in the context of neurodegeneration and to explore its potential as a therapeutic target. By unraveling the intricate relationship between iron homeostasis disorders, oxidative damage, and lipid metabolism disturbances in these diseases, new intervention targets are revealed. It offers a new dimension to the management of neurocognitive impairments in Alzheimer's and Parkinson's diseases. The implications of these findings extend beyond just Alzheimer's and Parkinson's diseases. They also have relevance with other neurological conditions characterized by oxidative stress and iron dysregulation. This review contributes to increased knowledge of ferroptosis and provides a foundational understanding that could lead to the development of innovative therapeutic strategies. Ultimately, it may alleviate the development of neurodegenerative diseases and improve cognitive function by preventing ferroptosis, which has not only academic significance but also potential clinical significance.