Effects of alloferon and its analogues on reproduction and development of the Tenebrio molitor beetle.

As the most numerous group of animals on Earth, insects are found in almost every ecosystem. Their useful role in the environment is priceless; however, for humans, their presence may be considered negative or even harmful. For years, people have been trying to control the number of pests by using synthetic insecticides, which eventually causes an increased level of resistance to applied compounds. The effects of synthetic insecticides have encouraged researchers to search for alternatives and thus develop safe compounds with high specificity. Using knowledge about the physiology of insects and the functionality of compounds of insect origin, a new class of bioinsecticides called peptidomimetics, which are appropriately modified insect analogues, was created. One promising compound that might be successfully modified is the thirteen amino acid peptide alloferon (HGVSGHGQHGVHG), which is obtained from the hemolymph of the blue blowfly Calliphora vicinia. Our research aimed to understand the physiological properties of alloferon and the activity of its peptidomimetics, which will provide the possibility of using alloferon or its analogues in the pharmaceutical industry, as a drug or adjuvant, or in agriculture as a bioinsecticide. We used alloferon and its three peptidomimetics, which are conjugates of the native peptide with three unsaturated fatty acids with various chain lengths: caprylic, myristic, and palmitic. We tested their effects on the morphology and activity of the reproductive system and the embryogenesis of the Tenebrio molitor beetle. We found that the tested compounds influenced the growth and maturation of ovaries and the expression level of the vitellogenin gene. The tested compounds also influenced the process of egg laying, embryogenesis, and offspring hatching, showing that alloferon might be a good peptide for the synthesis of effective bioinsecticides or biopharmaceuticals.

The allatotropin/orexin system as an example of immunomodulatory properties of neuropeptides.

The central nervous system (CNS) plays a critical role in signal integration in animals and allows the orchestration of life processes to maintain homeostasis. Current research clearly shows that inflammatory processes can also be modulated by the CNS via the neuroendocrine system. One of the neuropeptide families that participate in vertebrates in this process is orexins (OXs). Interestingly, our previous results suggested that a similar dependency may also exist between neuropeptides and immune system activity in insects. Due to the structural homology of orexin and allatotropin receptors and the functional similarity between these two neuropeptide families, the main aim of this research was to perform a complex analysis of the relationships between allatotropin (AT) and the insect immune response. Our results revealed functional similarities between vertebrate OXs and insect ATs. Similar effects were observed in the profile of the expression level of the gene encoding the AT precursor in the Tenebrio molitor nervous system and in the general action of Tenmo-AT on selected immune parameters of the tested beetles. Moreover, for the first time in insects, we confirmed the role of cytokines in the modulation of neuroendocrine system by determining the effect of Spätzle-like protein injection on the expression of genes encoding AT precursor and receptor. All these results are important for understanding the evolutionary basis of hormonal regulation of the immune response.

Cannabigerol-A useful agent restoring the muscular phospholipids milieu in obese and insulin-resistant Wistar rats?

Numerous strategies have been proposed to minimize obesity-associated health effects, among which phytocannabinoids appear to be effective and safe compounds. In particular, cannabigerol (CBG) emerges as a potent modulator of the composition of membrane phospholipids (PLs), which plays a critical role in the development of insulin resistance. Therefore, here we consider the role of CBG treatment on the composition of PLs fraction with particular emphasis on phospholipid subclasses (e.g., phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI)) in the red gastrocnemius muscle of Wistar rats fed the standard or high-fat, high-sucrose (HFHS) diet. The intramuscular PLs content was determined by gas-liquid chromatography and based on the composition of individual FAs, we assessed the stearoyl-CoA desaturase 1 (SCD1) index as well as the activity of n-3 and n-6 polyunsaturated fatty acids (PUFAs) pathways. Expression of various proteins engaged in the inflammatory pathway, FAs elongation, and desaturation processes was measured using Western blotting. Our research has demonstrated the important association of obesity with alterations in the composition of muscular PLs, which was significantly improved by CBG supplementation, enriching the lipid pools in n-3 PUFAs and decreasing the content of arachidonic acid (AA), which in turn influenced the activity of PUFAs pathways in various PLs subclasses. CBG also inhibited the local inflammation development and profoundly reduced the SCD1 activity. Collectively, restoring the PLs homeostasis of the myocyte membrane by CBG indicates its new potential medical application in the treatment of obesity-related metabolic disorders.

Short neuropeptide F in integrated insect physiology. / 昆虫生理中短神经肽Fçš„åŠŸèƒ½ç ”ç©¶è¿›å±•.

The short neuropeptide F (sNPF) family of peptides is a multifunctional group of neurohormones involved in the regulation of various physiological processes in insects. They have been found in a broad spectrum of species, but the number of isoforms in the precursor molecule varies from one to four. The receptor for sNPF (sNPFR), which belongs to the G protein-coupled receptor family, has been characterized in various insect orders and was shown to be an ortholog of the mammalian prolactin-releasing peptide receptor (PrPR). The sNPF signaling pathway interacts with other neurohormones such as insulin-like peptides, SIFamide, and pigment-dispersing factors (PDFs) to regulate various processes. The main physiological function of sNPF seems to be involved in the regulation of feeding, but the observed effects are species-specific. sNPF is also connected with the regulation of foraging behavior and the olfactory system. The influence of sNPF on feeding and thus energy metabolism may also indirectly affect other vital processes, such as reproduction and development. In addition, these neurohormones are involved in the regulation of locomotor activity and circadian rhythm in insects. This review summarizes the current state of knowledge about the sNPF system in insects.

The Role of Oxidative Stress and Inflammatory Parameters in Heart Failure.

Heart failure (HF) remains a major medical and social problem. The NT-pro-brain natriuretic peptide (NT-proBNP) and its active form, brain-type natriuretic peptide (BNP), in a simple blood test are the gold-standard biomarkers for HF diagnosis. However, even good biomarkers such as natriuretic peptides fail to predict all the risks associated with HF due to the diversity of the mechanisms involved. The pathophysiology of HF is determined by numerous factors, including oxidative stress, inflammation, neuroendocrine activation, pathological angiogenesis, changes in apoptotic pathways, fibrosis and vascular remodeling. High readmission and mortality rates prompt a search for new markers for the diagnosis, prognosis and treatment of HF. Oxidative-stress-mediated inflammation plays a crucial role in the development of subsequent changes in the failing heart and provides a new insight into this complex mechanism. Oxidative stress and inflammatory biomarkers appear to be a promising diagnostic and prognostic tool in patients with HF. This systematic review provides an overview of the current knowledge about oxidative stress and inflammation parameters as markers of HF.

Association of NT-proBNP and sST2 with Left Ventricular Ejection Fraction and Oxidative Stress in Patients with Stable Dilated Cardiomyopathy.

The aim of this study was to analyze the relationship between levels of sST2, NT-proBNP and oxidative stress markers in patients with reduced ejection fraction (HFrEF) due to non-ischemic cardiomyopathy. A total of 88 patients with HFrEF were divided into four groups based on left ventricular ejection fraction (≤25% and >25%) and NYHA functional class (group 1-LVEF > 25% and NYHA class I or II; group 2-LVEF > 25% and NYHA class III or IV; group III-LVEF ≤ 25% and NYHA class I or II; group IV-LVEF ≤ 25% and NYHA class III or IV). In 39 (44.32%) patients LVEF was reduced below 25%, and 22 of them (56.41%) were in NYHA functional class III/IV. Of the 49 (55.68%) patients with LVEF ≥ 25%, only 18.37% were in NYHA functional class III/IV (p < 0.001). Patients with LVEF ≥ 25% had lower levels of NT-proBNP, total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI). The levels of NT-proBNP but not sST-2 correlated positively with NYHA functional class (p < 0.001) and negatively with LVEF (p < 0.001). The levels of sST-2 were associated with increased TAC (p = 0.009) and uric acid (p = 0.040). These findings indicate that only NT-proBNP was related to the severity of heart failure, whereas sST2 correlated with total antioxidant capacity. Therefore, in stable patients with HFrEF due to dilated cardiomyopathy, sST2 may be an additional biomarker reflecting the redox status, but not the severity of heart failure.

Anti-inflammatory effects of cannabidiol in early stages of neuroinflammation induced by high-fat diet in cerebral cortex of rats.

High-fat diet (HFD) contributes to neuroinflammation forming, hence it is crucial to find safe and effective substances that are able to counteract its progress. The anti-inflammatory properties of phytocannabinoids acquired from the Cannabis plant have been widely acknowledged. We evaluated the effects of cannabidiol (CBD) treatment on induced by applying HFD early stages of neuroinflammation in Wistar rat cerebral cortex. In our 7-week experiment, CBD was injected intraperitoneally over the last 14days at a dose of 10 mg/kg of body weight once a day. The level of arachidonic acid, a precursor to pro-inflammatory eicosanoids, decreased in all analysed lipid classes after CBD administration to the HFD group. Moreover, the extent of diminishing the activity of the omega-6 (n-6) fatty acid pathway by CBD was the greatest in diacylglycerols and phospholipids. Surprisingly, CBD was also capable of downregulating the activity of the omega-3 (n-3) pathway. The expression of enzymes involved in the synthesis of the eicosanoids was significantly increased in the HFD group and subsequently lowered by CBD. Significant changes in various cytokines levels were also discovered. Our results strongly suggest the ability of CBD to reduce the formation of lipid inflammation precursors in rat cerebral cortex, as a primary event in the development of neurodegenerative diseases. This can raise hopes for the future use of this cannabinoid for therapeutic purposes since it is a substance lacking lasting and severe side effects.

How Does CBG Administration Affect Sphingolipid Deposition in the Liver of Insulin-Resistant Rats?

BACKGROUND: Cannabigerol (CBG), a non-psychotropic phytocannabinoid found in Cannabis sativa plants, has been the focus of recent studies due to its potential therapeutic properties. We proposed that by focusing on sphingolipid metabolism, which plays a critical role in insulin signaling and the development of insulin resistance, CBG may provide a novel therapeutic approach for metabolic disorders, particularly insulin resistance. METHODS: In a rat model of insulin resistance induced by a high-fat, high-sucrose diet (HFHS), we aimed to elucidate the effect of intragastrically administered CBG on hepatic sphingolipid deposition and metabolism. Moreover, we also elucidated the expression of sphingolipid transporters and changes in the sphingolipid concentration in the plasma. RESULTS: The results, surprisingly, showed a lack of changes in de novo ceramide synthesis pathway enzymes and significant enhancement in the expression of enzymes involved in ceramide catabolism, which was confirmed by changes in hepatic sphingomyelin, sphinganine, sphingosine-1-phosphate, and sphinganine-1-phosphate concentrations. CONCLUSIONS: The results suggest that CBG treatment may modulate sphingolipid metabolism in the liver and plasma, potentially protecting the liver against the development of metabolic disorders such as insulin resistance.

Concentration-Dependent Attenuation of Pro-Fibrotic Responses after Cannabigerol Exposure in Primary Rat Hepatocytes Cultured in Palmitate and Fructose Media.

Hepatic fibrosis is a consequence of liver injuries, in which the overproduction and progressive accumulation of extracellular matrix (ECM) components with the simultaneous failure of matrix turnover mechanisms are observed. The aim of this study was to investigate the concentration-dependent influence of cannabigerol (CBG, Cannabis sativa L. component) on ECM composition with respect to transforming growth factor beta 1 (TGF-ß1) changes in primary hepatocytes with fibrotic changes induced by palmitate and fructose media. Cells were isolated from male Wistar rats' livers in accordance with the two-step collagenase perfusion technique. This was followed by hepatocytes incubation with the presence or absence of palmitate with fructose and/or cannabigerol (at concentrations of 1, 5, 10, 15, 25, 30 µM) for 48 h. The expression of ECM mRNA genes and proteins was determined using PCR and Western blot, respectively, whereas media ECM level was evaluated using ELISA. Our results indicated that selected low concentrations of CBG caused a reduction in TGF-ß1 mRNA expression and secretion into media. Hepatocyte exposure to cannabigerol at low concentrations attenuated collagen 1 and 3 deposition. The protein and/or mRNA expressions and MMP-2 and MMP-9 secretion were augmented using CBG. Considering the mentioned results, low concentrations of cannabigerol treatment might expedite fibrosis regression and promote regeneration.

Therapeutic effect of cannabidiol on myocardial arachidonic acid content in various lipid fractions in a rat model of obesity.

The study explored the potential protective influence of cannabidiol (CBD) on myocardial inflammation state, with a special focus on arachidonic acid (AA), and oxidative balance in lipid overload conditions. The 7-week experiment was conducted on male Wistar rats receiving standard or high-fat diet (HFD) with intraperitoneal CBD injections for the last 14 days. The n-3 and n-6 polyunsaturated fatty acids (PUFAs) activities and AA concentration in selected fractions were evaluated by gas-liquid chromatography (GLC). The expression of proteins was determined by Western blot and the concentration of different parameters by ELISA, colorimetric, or multiplex assay kits. Our results revealed that CBD increased n-3 PUFAs activity in phospholipid and triacylglycerol fractions, and decreased AA content in the HFD group, especially in the phospholipid pool. Simultaneously, CBD decreased the expression of nuclear factor kappa B, cyclooxygenase-1, and - 2, resulting in the reduction of prostaglandin E2 and the increment of prostaglandin I2. CBD appears to be relatively safe for the treatment of obesity-induced heart disease, as it has anti-inflammatory and partially antioxidative properties.

Cannabidiol improves muscular lipid profile by affecting the expression of fatty acid transporters and inhibiting de novo lipogenesis.

Obesity is one of the principal public health concerns leading to disturbances in glucose and lipid metabolism, which is a risk factor for several chronic diseases, including insulin resistance, type 2 diabetes mellitus, and cardiovascular diseases. In recent years, it turned out that cannabidiol (CBD) is a potential therapeutic agent in the treatment of obesity and its complications. Therefore, in the present study, we used CBD therapy (intraperitoneal injections in a dose of 10 mg/kg of body mass for 14 days) in a rat model of obesity induced by a high-fat diet (HFD). Gas-liquid chromatography and Western blotting were applied in order to determine the intramuscular lipid content and total expression of selected proteins in the white and red gastrocnemius muscle, respectively. Based on fatty acid composition, we calculated de novo lipogenesis ratio (16:0/18:2n-6), desaturation ratio (18:1n-9/18:0), and elongation ratios (18:0/16:0, 20:0/18:0, 22:0/20:0 and 24:0/22:0), in the selected lipid fractions. Two-week CBD administration significantly reduced the intramuscular fatty acids (FAs) accumulation and inhibited de novo lipogenesis in different lipid pools (in the free fatty acid, diacylglycerol, and triacylglycerol fractions) in both muscle types, which coincided with a decrease in the expression of membrane fatty acid transporters (fatty acid translocase, membrane-associated fatty acid binding protein, and fatty acid transport proteins 1 and 4). Moreover, CBD application profoundly improved the elongation and desaturation ratios, which was in line with downregulated expression of enzymes from the family of elongases and desaturases regardless of the metabolism presented by the muscle type. To our knowledge, this study is the first that outlines the novel effects of CBD action on skeletal muscle with different types of metabolism (oxidative vs. glycolytic).

Coumestrol as a new substance that may diminish lipid precursors of the inflammation in steatotic primary rat hepatocytes.

Coumestrol is a phytoestrogen found in various plant foods. Increasing evidence ascertained its robust anti-inflammatory, anti-oxidative properties likewise ability to mitigate insulin resistance. Thus, it may be a potential medicine in the treatment of many metabolic disorders, including obesity, type 2 diabetes (T2D) as well as non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to shed some light on its influence on the accumulation of certain lipid fractions and the expression of pro-inflammatory proteins in primary rat hepatocytes during the lipid-overload state. The cells were isolated from the male Wistar rat's liver with the use of collagenase perfusion. It was followed by incubation of the cells with the presence or absence of palmitic acid and/or coumestrol. The accumulation of lipid fractions was assessed by gas-liquid chromatography (GLC) whereas the expression of the proteins was evaluated by the Western blot technique. Treatment with coumestrol in the state of increased fatty acids availability led to the deposition of triacylglycerols rather than diacylglycerols, significantly decreased expression of proinflammatory and profibrotic cytokines, especially interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), as well as transforming growth factor ß (TGF-ß), and nuclear factor κß (NF-κß). Also, we observed a substantial diminution in proinflammatory enzymes expression. Taking into consideration the direction of the aforementioned changes, we may assume that coumestrol can ameliorate the array of factors leading to the development of steatosis, likewise counteracting progression to steatohepatitis, thus it may be a step forward to the long-awaited breakthrough in the treatment of NAFLD.

Antheraea peptide and its analog: Their influence on the maturation of the reproductive system, embryogenesis, and early larval development in Tenebrio molitor L. beetle.

In recent years, many new immunologically active peptides from insects have been identified. Unfortunately, in most cases, their physiological functions are not fully known. One example is yamamarin, a pentapeptide isolated from the caterpillars of the Antheraea yamamai moth. This peptide has strong antiproliferative properties and is probably involved in the regulation of diapause. Additionally, antiviral activity was discovered. The results of the research presented in this paper are, to our knowledge, the first attempt to characterize the biological effects of yamamarin on the functioning of the reproductive processes and embryonic development of insects using a model species, the beetle Tenebrio molitor, a commonly known pest of grain storage. Simultaneously, we tested the possible activity of the molecule in an in vivo system. In this research, we present the multifaceted effects of yamamarin in this beetle. We show that yamamarin influences ovarian growth and development, maturation of terminal oocytes, level of vitellogenin gene transcript, the number of laid eggs, duration of embryonic development, and larval hatching. In experiments with palmitic acid-conjugated yamamarin (C16-yamamarin), we also showed that this peptide is a useful starting molecule for the synthesis of biopharmaceuticals or new peptidomimetics with gonadotropic activity and effects on embryonic development. The data obtained additionally provide new knowledge about the possible function of yamamarin in insect physiology, pointing to the important role of this pentapeptide as a regulator of reproductive processes and embryonic development in a heterologous bioassay with T. molitor.

Tachykinin-related peptides modulate immune-gene expression in the mealworm beetle Tenebrio molitor L.

Tachykinins (TKs) are a group of conserved neuropeptides. In insects, tachykinin-related peptides (TRPs) are important modulators of several functions such as nociception and lipid metabolism. Recently, it has become clear that TRPs also play a role in regulating the insect immune system. Here, we report a transcriptomic analysis of changes in the expression levels of immune-related genes in the storage pest Tenebrio molitor after treatment with Tenmo-TRP-7. We tested two concentrations (10-8 and 10-6 M) at two time points, 6 and 24 h post-injection. We found significant changes in the transcript levels of a wide spectrum of immune-related genes. Some changes were observed 6 h after the injection of Tenmo-TRP-7, especially in relation to its putative anti-apoptotic action. Interestingly, 24 h after the injection of 10-8 M Tenmo-TRP-7, most changes were related to the regulation of the cellular response. Applying 10-6 M Tenmo-TRP-7 resulted in the downregulation of genes associated with humoral responses. Injecting Tenmo-TRP-7 did not affect beetle survival but led to a reduction in haemolymph lysozyme-like antibacterial activity, consistent with the transcriptomic data. The results confirmed the immunomodulatory role of TRP and shed new light on the functional homology between TRPs and TKs.

Molecular Advances in MAFLD-A Link between Sphingolipids and Extracellular Matrix in Development and Progression to Fibrosis.

Metabolic-Associated Fatty Liver Disease (MAFLD) is a major cause of liver diseases globally and its prevalence is expected to grow in the coming decades. The main cause of MAFLD development is changed in the composition of the extracellular matrix (ECM). Increased production of matrix molecules and inflammatory processes lead to progressive fibrosis, cirrhosis, and ultimately liver failure. In addition, increased accumulation of sphingolipids accompanied by increased expression of pro-inflammatory cytokines in the ECM is closely related to lipogenesis, MAFLD development, and its progression to fibrosis. In our work, we will summarize all information regarding the role of sphingolipids e.g., ceramide and S1P in MAFLD development. These sphingolipids seem to have the most significant effect on macrophages and, consequently, HSCs which trigger the entire cascade of overproduction matrix molecules, especially type I and III collagen, proteoglycans, elastin, and also tissue inhibitors of metalloproteinases, which as a result cause the development of liver fibrosis.

Solanaceae glycoalkaloids: α-solanine and α-chaconine modify the cardioinhibitory activity of verapamil.

CONTEXT: Solanaceae glycoalkaloids (SGAs) possess cardiomodulatory activity. OBJECTIVE: This study investigated the potential interaction between verapamil and glycoalkaloids. MATERIAL AND METHODS: The cardioactivity of verapamil and glycoalkaloids (α-solanine and α-chaconine) was tested in adult beetle (Tenebrio molitor) myocardium in vitro using microdensitometric methods. The myocardium was treated with pure substances and mixtures of verapamil and glycoalkaloids for 9 min with saline as a control. Two experimental variants were used: simultaneous application of verapamil and glycoalkaloids or preincubation of the myocardium with one of the compounds followed by perfusion with a verapamil solution. We used 9 × 10-6-5 × 10-5 M and 10-9-10-5 M concentration for verapamil and glycoalkaloids, respectively. RESULTS: Verapamil, α-solanine and α-chaconine showed cardioinhibitory activity with IC50 values equal to 1.69 × 10-5, 1.88 × 10-7 and 7.48 × 10-7 M, respectively. When the glycoalkaloids were applied simultaneously with verapamil, an antagonistic effect was observed with a decrease in the maximal inhibitory effect and prolongation of t50 and the recovery time characteristic of verapamil. We also confirmed the expression of two transcript forms of the gene that encodes the α1 subunit of L-type calcium channels in the myocardium and brain with equal transcription levels of both forms in the myocardium and significant domination of the shorter form in the brain of the insect species tested. DISCUSSION AND CONCLUSIONS: The results show that attention to the composition of the daily diet during therapy with various drugs is particularly important. In subsequent studies, the nature of interaction between verapamil and SGAs on the molecular level should be checked, and whether this interaction decreases the efficiency of cardiovascular therapy with verapamil in humans.

Distinct Effects of Cannabidiol on Sphingolipid Metabolism in Subcutaneous and Visceral Adipose Tissues Derived from High-Fat-Diet-Fed Male Wistar Rats.

Available data suggest that cannabidiol (CBD) may ameliorate symptoms of insulin resistance by modulating the sphingolipid concentrations in particular organs. However, it is not entirely clear whether its beneficial actions also involve adipose tissues in a state of overnutrition. The aim of the study was to evaluate the effect of CBD on sphingolipid metabolism pathways and, as a result, on the development of insulin resistance in subcutaneous (SAT) and visceral (VAT) adipose tissues of an animal model of HFD-induced insulin resistance. Our experiment was performed on Wistar rats that were fed with a high-fat diet and/or received intraperitoneal CBD injections. We showed that CBD significantly lowered the ceramide content in VAT by reducing its de novo synthesis and increasing its catabolism. However, in SAT, CBD decreased the ceramide level through the inhibition of salvage and de novo synthesis pathways. All of these changes restored adipose tissues' sensitivity to insulin. Our study showed that CBD sensitized adipose tissue to insulin by influencing the metabolism of sphingolipids under the conditions of increased availability of fatty acids in the diet. Therefore, we believe that CBD use may be considered as a potential therapeutic strategy for treating or reducing insulin resistance, T2DM, and metabolic syndrome.

Asymptomatic Survivors of Childhood Acute Lymphoblastic Leukemia Demonstrate a Biological Profile of Inflamm-Aging Early in Life.

Childhood acute lymphoblastic leukemia (ALL) survivors are at higher risk of developing many late effects later in life. They experience multiple health problems that have significant public health implications, such as frailty, premature onset of lifestyle diseases, and second tumors. There is some evidence that chronic inflammation causes accelerated aging in childhood cancer survivors; however, the available data are very limited. The aim of the study was to evaluate the broad panel of cytokines among asymptomatic ALL survivors after anticancer treatment. The study included 56 subjects with a mean age of 16.11 ± 3.98 years. The commercially available Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay and Bio-Plex TGF-ß Assay were used for simultaneous determination of 48 cytokines and 3 isoforms of TGF-ß. Among 51 tested cytokines, the levels of 33 were statistically significantly higher in ALL survivors than in the control group (p < 0.05). Increased levels of pro-inflammatory cytokines, including the IL-1 family (IL-1 ß, IL-1Ra; p < 0.0001), IL-6 (p < 0.001), IL-17 (p < 0.001), IL-18 (p < 0.05), TNFα (p < 0.01), IFNα2 (p < 0.05), and IFNγ (p < 0.01), were found elevated in the entire study group, compared with the controls. Subjects treated previously according to the high-risk protocol had higher IL-18 levels than low- and intermediate-risk groups (p < 0.05). Elevated levels of IL-1ra, IL-6, IL-12 (p70), IL-17, LIF, M-CSF, CSF, and VEGF were found in ALL survivors treated before the age of 5, compared with subjects treated over 5 years of age (p < 0.05). Moreover, individuals who received radiotherapy presented elevated levels of both IL-18 (p < 0.05) and MIG (p < 0.05). In conclusion, we found that young asymptomatic survivors after ALL treatment demonstrated a biological profile of complex low-grade chronic inflammation.

Biomarkers of Glucose Metabolism Alterations and the Onset of Metabolic Syndrome in Survivors of Childhood Acute Lymphoblastic Leukemia.

Owing to advances in treatment modalities and supportive care, overall survival rates have reached up to 90% among children with acute lymphoblastic leukemia (ALL). However, due to the underlying illness and therapy, they are at a greater risk of developing lifestyle diseases. Hence, special attention is paid to early detection of the components of metabolic syndrome (MetS). This study aimed at investigating the association of plasma levels of nine diabetes markers with being overweight and components of MetS in ALL survivors. The study included 56 subjects with mean age of 12.36 ± 5.15 years. The commercially available Bio-Plex Pro Human Diabetes 10-Plex Panel kit was used to evaluate levels of diabetes biomarkers. ALL survivors presented statistically higher concentrations of GIP (p = 0.026), glucagon (p = 0.001), leptin (p = 0.022), and PAI-1 (p = 0.047), whereas the concentration of ghrelin was lower (p < 0.001) compared to the control group. Moreover, subjects within normal BMI range showed higher GIP (p = 0.005) and lower ghrelin concentration (p < 0.001) compared to healthy peers. At least one risk factor of MetS was present in 58.9% of participants, who showed significantly higher levels of C-peptide (p = 0.028), leptin (p = 0.003), and PAI-1 (p = 0.034) than survivors who did not meet any MetS criteria. In conclusion, ALL survivors are at greater risk of disturbances in carbohydrate metabolism. Understanding the pathogenesis and applicability of diabetes markers is crucial for developing strategies to prevent metabolic syndrome in ALL survivors.

The Endocannabinoid System and Physical Activity-A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders.

Rapidly increasing worldwide prevalence of obesity and related pathologies encompassing coronary heart disease, hypertension, metabolic syndrome, or type 2 diabetes constitute serious threats to global health and are associated with a significantly elevated risk of premature death. Considering the enormous burden of these pathologies, novel therapeutic and preventive patterns are indispensable. Dysregulation of one of the most complex biological systems in the human body namely, the endocannabinoid system (ECS) may result in metabolic imbalance and development of insulin resistance, type 2 diabetes, or non-alcoholic fatty liver disease. Furthermore, many studies showed that physical exercises, depending on their type, intensity, and frequency, exert various alterations within the ECS. Emerging evidence suggests that targeting the ECS via physical activity may produce robust beneficial effects on the course of metabolic pathologies. However, the data showing a direct correlation between the ECS and physical activity in the aspect of metabolic health are very scarce. Therefore, the aim of this review was to provide the most up-to-date state of knowledge about the interplay between the ECS activity and physical exercises in the novel therapeutic and preventive approach toward metabolic pathologies. We believe that this paper, at least in part, will fulfill the existing gap in knowledge and encourage researchers to further explore this very complex yet interesting link between the ECS, its action in physical activity, and subsequent positive outcomes for metabolic health.