Study on the breeding ginkgo (ginkgo biloba l.) in Tashkent oasis

This article presents the results of research on the biochemical composition of green and yellowing leaves of 64-year-old bipedal ginkgo (Ginkgo biloba L.) seed and pollen trees growing in the Botanical Garden of the Academy of Sciences of Uzbekistan, introduced to Uzbekistan in the last century. Biochemical analyzes recorded the presence of 6 types of vitamins and 44 macro- and micronutrients in the leaves of the ginkgo tree. Vitamin C levels were found to be lower in the seed tree than in the pollen tree. The amount was 35.8 mg/% in the green leaves of the seed tree and 34.4 mg/% in the yellowed leaves. Ginkgo leaves contain important macro-and micronutrients such as Ca, Mg, K, Al, Fe, Cu, Mn, Zn, Mo, Co, I, Se, which are necessary for the vital activity of the human body and normal metabolism. The green leaves of the two-leafed ginkgo pollen tree contained 27577.288 mg/l of calcium, 11562.299 mg/l of potassium, the leaves of the seed tree 13912.903 mg/l of calcium and 7491.462 mg/l of potassium. At the same time, the green leaves of ginkgo contain 3073.807 mg/l – 7977.459 mg/l magnesium, 4353.72-5003.88 mg/l phosphorus, 501.073-515.343 mg/l sodium, 779.750 mg/l– the presence of silicon in the amount of 844.039 mg/l and iron in the amount of 373.023 mg/l – 655.148 mg/l was determined.

Involvement of impaired CD8+ mucosal-associated invariant T cells and myeloid-derived suppressor cells in polycystic ovary syndrome

Background Immune dysfunction is one of the mechanisms to promote polycystic ovary syndrome (PCOS). Various immune cells have been reported to be involved in the development of PCOS. Meanwhile, the disturbance of metabolism is closely related to PCOS. The aim of this study is to explore the association of mucosal-associated invariant T (MAIT) cells and myeloid-derived suppressor cells (MDSCs) with the metabolic dysfunction in PCOS. Methods 68 PCOS patients and 40 controls were recruited in this study and we collected the peripheral blood of participants’ during their follicular phase. The frequencies of MAIT cells and MDSCs were determined by flow cytometry after being stained with different monoclonal antibodies. And the concentrations of cytokines were determined by ELISA. Results Compared to controls with normal metabolism, the frequency of MDSCs, CD8+MAIT cells and CD38+CD8+MAIT cells were significantly decreased in PCOS patients with normal metabolism, however, proportion of CD4+MAIT cells exhibited a noticeable increase. Similar results of CD8+MAIT, CD38+CD8+MAIT cells and reduced expression of IL-17 were observed in PCOS patients with metabolic dysfunction as compared to controls with metabolic disorders. PCOS patients with excessive testosterone levels displayed significantly decreased levels of CD8+MAIT, CD38+CD8+MAIT cells, MDSCs and Mo-MDSCs as compared to PCOS patients with normal testosterone concentrations. PCOS patients with abnormal weight showed a lower level and activation of CD8+MAIT cells. On the contrary, they displayed an enrichment of CD4+MAIT cells. PCOS patients with glucose metabolic disorder displayed a remarkable dysregulation of MDSCs and Mo-MDSCs. MDSCs were positively correlated with MAIT cells. Negative correlations between the frequency of CD8+MAIT cells, CD38+CD8+MAIT cells and body mass index were revealed. CD4+MAIT cells positively correlated with BMI. Mo-MDSCs were found to be negatively related to the levels of 2hour plasma glucose and HOMA-IR index. Conclusion The impairment of CD8+MAIT cells and MDSCs is involved in the metabolic dysfunction of PCOS.

Appetite Regulation of TLR4-Induced Inflammatory Signaling

Appetite is the basis for obtaining food and maintaining normal metabolism. Toll-like receptor 4 (TLR4) is an important receptor expressed in the brain that induces inflammatory signaling after activation. Inflammation is considered to affect the homeostatic and non-homeostatic systems of appetite, which are dominated by hypothalamic and mesolimbic dopamine signaling. Although the pathological features of many types of inflammation are known, their physiological functions in appetite are largely unknown. This review mainly addresses several key issues, including the structures of the homeostatic and non-homeostatic systems. In addition, the mechanism by which TLR4-induced inflammatory signaling contributes to these two systems to regulate appetite is also discussed. This review will provide potential opportunities to develop new therapeutic interventions that control appetite under inflammatory conditions.

Camptothecin Encapsulated in β-Cyclodextrin-EDTA-Fe3O4 Nanoparticles Induce Metabolic Reprogramming Repair in HT29 Cancer Cells through Epigenetic Modulation: A Bioinformatics Approach

Cancer progresses through a distinctive reprogramming of metabolic pathways directed by genetic and epigenetic modifications. The hardwired changes induced by genetic mutations are resilient, while epigenetic modifications are softwired and more vulnerable to therapeutic intervention. Colon cancer is no different. This gives us the need to explore the mechanism as an attractive therapeutic target to combat colon cancer cells. We have previously established the enhanced therapeutic efficacy of a newly formulated camptothecin encapsulated in β-cyclodextrin-EDTA-Fe3O4 nanoparticles (CPT-CEF) in colon cancer cells. We furthered this study by carrying out RNA sequencing (RNA-seq) to underscore specific regulatory signatures in the CPT-CEF treated versus untreated HT29 cells. In the study, we identified 95 upregulated and 146 downregulated genes spanning cellular components and molecular and metabolic functions. We carried out extensive bioinformatics analysis to harness genes potentially involved in epigenetic modulation as either the cause or effect of metabolic rewiring exerted by CPT-CEF. Significant downregulation of 13 genes involved in the epigenetic modulation and 40 genes from core metabolism was identified. Three genes, namely, DNMT-1, POLE3, and PKM-2, were identified as the regulatory overlap between epigenetic drivers and metabolic reprogramming in HT29 cells. Based on our results, we propose a possible mechanism that intercepts the two functional axes, namely epigenetic control, and metabolic modulation via CPT-CEF in colon cancer cells, which could skew cancer-induced metabolic deregulation towards metabolic repair. Thus, the study provides avenues for further validation of transcriptomic changes affected by these deregulated genes at epigenetic level, and ultimately may be harnessed as targets for regenerating normal metabolism in colon cancer with better treatment potential, thereby providing new avenues for colon cancer therapy.

Molecular Mechanisms of Ferroptosis and Its Roles in Hematologic Malignancies

Cell death is essential for the normal metabolism of human organisms. Ferroptosis is a unique regulated cell death (RCD) mode characterized by excess accumulation of iron-dependent lipid peroxide and reactive oxygen species (ROS) compared with other well-known programmed cell death modes. It has been currently recognized that ferroptosis plays a rather important role in the occurrence, development, and treatment of traumatic brain injury, stroke, acute kidney injury, liver damage, ischemia–reperfusion injury, tumor, etc. Of note, ferroptosis may be explained by the expression of various molecules and signaling components, among which iron, lipid, and amino acid metabolism are the key regulatory mechanisms of ferroptosis. Meanwhile, tumor cells of hematological malignancies, such as leukemia, lymphoma, and multiple myeloma (MM), are identified to be sensitive to ferroptosis. Targeting potential regulatory factors in the ferroptosis pathway may promote or inhibit the disease progression of these malignancies. In this review, a systematic summary was conducted on the key molecular mechanisms of ferroptosis and the current potential relationships of ferroptosis with leukemia, lymphoma, and MM. It is expected to provide novel potential therapeutic approaches and targets for hematological malignancies.

Glomerular Hyperfiltration Interacts With Abnormal Metabolism to Enhance Arterial Stiffness in Middle-Aged and Elderly People

Introduction: Glomerular hyperfiltration (GHF) is an early kidney injury. We investigated whether GHF is associated with arterial stiffness expressed by increase of brachial–ankle pulse wave velocity (baPWV) and pulse pressure (PP), and whether the coexistence of GHF and abnormal metabolism increases the risk of arterial stiffness.Methods: In this prospective cohort study, 2,133 non-chronic kidney disease (CKD) participants aged ≥40 years were followed for a mean period of 3.3 years. The extent of arterial stiffness was expressed by measures of baPWV and PP. GHF was defined as eGFR exceeding the age- and sex-specific 90th percentile. Multivariate logistic regression models were used to assess the association between GHF/abnormal metabolism and increased baPWV/PP. The interaction indexes of GHF and abnormal metabolism on arterial stiffness were calculated based on the OR in a multivariate logistic regression model.Results: GHF alone was not associated with increased baPWV or PP in all participants in this study. However, when GHF coexisted with abnormal metabolism, the risk of increased PP increased 3.23-fold [OR = 3.23(1.47–7.13)] compared with participants with normal filtration and normal metabolism, in which the interaction accounted for 55.1% of the total effect and 79.8% of the effect from GHF and abnormal metabolism. After subtracting the independent effects of GHF and abnormal metabolism, their combined effect still resulted in a 1.78-fold increase in PP.Conclusion: GHF could interact with abnormal metabolism to significantly enhance arterial stiffness. Since abnormal metabolism commonly exists in the general population, even slight changes in renal function should be distinguished to prevent arterial stiffness risk.

Prediabetes. A new paradigm for early prevention of cardiovascular disease

This literature review focuses on the association of prediabetes with cardiovascular disease (CVD). Recently, much attention has been paid to the study of prediabetes due to its extremely high prevalence and strong association with a high risk of developing serious complications that worsen the quality of kife of patients. Prediabetes is not only a metabolic condition with a high risk of developing type 2 diabetes mellitus (T2DM), but also CVD and death from all causes. This association is true for both patients who do not yet have CVD and those with a history of CVD. Also during the COVID-19 pandemic, attention is drawn to the fact that people with prediabetes have a higher risk of a severe course of infection, complications and a worse prognosis of the disease. This is associated with hyperglycemia, the presence of chronic systemic inflammation of a low degree of activity, impaired immune response mechanisms and a procoagulant state in patients with prediabetes, although these disorders are less developed than in patients with T2DM. Therefore, early screening of early disorders of normal metabolism. Since active early intervention at the stage of prediabetes helps to prevent the development of type 2 diabetes and CVD.

Molecular hydrogen as a possible therapeutic factor in complex rehabilitation therapy in patients with muscular skeletal disorders (literature review)

The paper presents an analysis of foreign scientific and medical data on the therapeutic factor — molecular hydrogen. The effectiveness of its application in the complex therapy of many diseases is revealed. The effect is achieved due to the small size of the mo­lecule, which passes through biological membranes and inhibits dangerous free radicals in the mitochondria, as well as in the nuc­leus, which reduces the possibility of DNA damaging. Molecular hydrogen neutralizes oxidants in the brain due to its ability to cross the blood-brain barrier. It normalizes the functions and metabolic processes in the body and, as an antioxidant, is selective: it does not affect the useful free radicals involved in important metabo­lic processes and selectively eliminates only the most dangerous oxidants — hydroxyl radicals. Interacting with them, hydrogen converts them into water molecules without the formation of by-products and chain reactions. Unlike other known antioxidants, molecular hydrogen does not disrupt normal metabolism, does not cause negative changes in cells, activates the body’s own anti­oxidant systems. The possibility and expediency of the use of molecular hydrogen in the case of pathology of the musculoskeletal system has been confirmed. The peculiarities of its effect on bone and cartilage tissue in the experiment are shown. It has been determined that the use of molecular hydrogen is a new pharmacological strategy aimed at the selective removal of ONOO—, and can be an effective method in the treatment of joint diseases. Because cartilage receives nutrients through a diffusion-loading mechanism, and molecular hydrogen penetrates rapidly into tissues, it can be useful for the prevention of diseases of joints of degenerative origin. It reduces oxidative stress and slows down the reduction of matrix proteins and inhibition of proteinase degradation. Its effectiveness has been proven after injuries to the spinal cord, muscles and tendons, comorbid diseases such as hypertension, coronary heart disease, diabetes and metabolic syndrome. Key words. Molecular hydrogen, hydrogen water, hydrogen inhalations, joint diseases, consequences of musculoskeletal injuries, comorbid pathology.

Sex Differences in Brain Tumor Glutamine Metabolism Reveal Sex-Specific Vulnerabilities to Treatment

Sex differences in normal metabolism are well described, but whether they persist in cancerous tissue is unknown. We assessed metabolite abundance in glioblastoma surgical specimens and found that male glioblastomas are enriched for amino acids, including glutamine. Using PET imaging, we found that gliomas in male patients exhibit significantly higher glutamine uptake. These sex differences were well-modeled in murine transformed astrocytes, in which male cells imported and metabolized more glutamine and were more sensitive to glutaminase 1 (GLS1) inhibition. The sensitivity to GLS1 inhibition in males was driven by their dependence on glutamine-derived glutamate for α-ketoglutarate synthesis and TCA cycle replenishment. Females were resistant to GLS inhibition through greater pyruvate carboxylase-mediated TCA cycle replenishment. Thus, clinically important sex differences exist in targetable elements of metabolism. Recognition of sex-biased metabolism is an opportunity to improve treatments for all patients through further laboratory and clinical research.

ANALYSIS OF VITAMIN D WITH INTRACTABLE DISEASES- A REVIEW.

Vitamin D is a fat-soluble, steroid hormone responsible for the phospho calcium mechanism. Mainly vitamin D encompasses a group of steroid compounds, namely the VitD2 (ergocalciferol) and the VitD3(cholecalciferol). It is an important requirement for normal functioning of the skeletal muscles, organs and normal metabolism. Providing Vitamin D supplementation to people with Diabetes (Type 1 and 2), Covid-19 positive and people with Thyroid problems showed improved glycaemic controls and regularized blood sugar levels, increase in immune response and regulating the Thyroid levels in the body. Vitamin D also adds to the innate immune system and also plays a major role in zinc metabolism which becomes a major reason for decreasing the symptoms of COVID-19 in the human body. Keywords: Vitamin D, Type 2 Diabetes Mellitus, Type 1 Diabetes Mellitus, Covid-19, Diabetic Neuropathy, Diabetic Nephropathy, Thyroid, Hypovitaminosis.