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Does metabolically healthy obesity exist? A 32-year-old man with BMI 78 kg/m2 — to treat or not to treat?

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GLP-1 agonists for physician

Cukrzyca została jako pierwsza choroba niezakaźna została uznana przez Organizację Narodów Zjednoczonych za epidemię. Jest chorobą interdyscyplinarną i wiąże się z wysokimi kosztami leczenia. Najczęściej występują zdar zenia sercowo-naczyniowe i mogą być pr zyczyną 80% zgonów chorych na cukrzycę. Organizacje Diabetologiczne, wśród nich Polskie Towarzystwo Diabetologiczne (PTD) w algorytmach leczenia cukrzycy typu 2 uwzględnia nową grupę leków hipoglikemizujących — agonistów glukagonopodobnego peptydu-1 (GLP-1). To leki wykorzystujące efekt inkretynowy w organizmie, ich działanie zależy od wzrostu poziomu glikemii. Skutecznie obniżają glikemię określoną w zmianie stężenia hemoglobiny glikowanej średnio o 1% (0,4−2,0%) z małym ryzykiem hipoglikemii. W badaniach klinicznych wykazano pozytywny wpływ na redukcję masy ciała, a otyłość jest kluczowym problemem w leczeniu pacjentów z cukrzycą typu 2. Leki te charakteryzują się również korzystnym oddziaływaniem na gospodarkę lipidową. Nie można pominąć działania obniżającego ciśnienie skurczowe i rozkurczowe krwi. Najczęściej spotykanym objawem ubocznym są dolegliwości ze strony układu pokarmowego, wraz ze stosowaniem ich siła jednak słabnie. Leki z grupy agonistów GLP-1 są zarejestrowane do stosowania u dorosłych z cukrzycą typu 2 w skojarzeniu z metforminą lub pochodną sulfonylomocznika, u których dotychczasowa kontrola glikemii jest niewystarczająca.Diabetes mellitus type 2 is the disease which was recognized by World Health Organization as an epidemic. Diabetes is the interdisciplinary disease and its connected with high costs of treatment. The most common complications are cardio-vascular diseases and it can be main reason (80%) of death. New type of hypoglycemic dr ugs, glucagon like peptide-1 agonists (GLP-1 agonists) were recognized by International Diabetes Associations and Polish Diabetes Association (PTD) in their algorithms. These drugs use incretin effect, which is depended on the glucose level. They reduce HBA1c level by 1% averagely with low risk of hypoglycemy. They showed during clinical trials, GLP-1 agonists have positive influence on reducing body weight. Obesity is the main problem in treatment patients with type 2 diabetes. Positive influence on lipid metabolism is characteristic of incretin’s drugs. One of the crucial features is hypotension effect this group of drugs. The most common side effects or adverse events associated with GLP-1 therapy were nausea, and occasionally vomiting. GLP-1 agonist are used for adult people with diabetes type 2 with metformin or sulfonylureas who are insufficiently controlled

Mitochondrial stress-dependent regulation of cellular protein synthesis

The production of newly synthesized proteins is vital for all cellular functions and is a determinant of cell growth and proliferation. The synthesis of polypeptide chains from mRNA molecules requires sophisticated machineries and mechanisms that need to be tightly regulated, and adjustable to current needs of the cell. Failures in the regulation of translation contribute to the loss of protein homeostasis, which can have deleterious effects on cellular function and organismal health. Unsurprisingly, the regulation of translation appears to be a crucial element in stress response mechanisms. This review provides an overview of mechanisms that modulate cytosolic protein synthesis upon cellular stress, with a focus on the attenuation of translation in response to mitochondrial stress. We then highlight links between mitochondrion-derived reactive oxygen species and the attenuation of reversible cytosolic translation through the oxidation of ribosomal proteins at their cysteine residues. We also discuss emerging concepts of how cellular mechanisms to stress are adapted, including the existence of alternative ribosomes and stress granules, and the regulation of co-translational import upon organelle stress

Is the retinol-binding protein 4 a possible risk factor for cardiovascular diseases in obesity?

Although many preventive and treatment approaches have been proposed, cardiovascular disease (CVD) remains one of the leading causes of deaths worldwide. Current epidemiological data require the specification of new causative factors, as well as the development of improved diagnostic tools to provide better cardiovascular management. Excessive accumulation of adipose tissue among patients suffering from obesity not only constitutes one of the main risk factors of CVD development but also alters adipokines. Increased attention is devoted to bioactive adipokines, which are also produced by the adipose tissue. The retinol-binding protein 4 (RBP4) has been associated with numerous CVDs and is presumably associated with an increased cardiovascular risk. With this in mind, exploring the role of RBP4, particularly among patients with obesity, could be a promising direction and could lead to better CVD prevention and management in this patient group. In our review, we summarized the current knowledge about RBP4 and its association with essential aspects of cardiovascular disease—lipid profile, intima-media thickness, atherosclerotic process, and diet. We also discussed the RBP4 gene polymorphisms essential from a cardiovascular perspective.info:eu-repo/semantics/publishedVersio

Immunoexpression of aromatase cytochrome P450 and 17β-hydroxysteroid dehydrogenase in women’s ovaries after menopause

BACKGROUND: Menopause results in a lack of regular menstrual cycles, leading to the reduction of estrogen production. On the other hand, ovarian androgen synthesis is still present at reduced levels and requires expression of several steroidogenic enzymes. METHODS: This study was performed on 104 postmenopausal women hospitalized due to uterine leiomyomas, endometriosis, and/or a prolapsed uterus. Patients were divided into three groups depending on the time from menopause. Group A patients experienced menopause 1–5 years before enrollment in the study (42 women). Group B included women who had their last menstruation 5–10 years before the study (40 women). Group C consisted of 22 women who were more than 10 years past menopause. Hysterectomy or removal of the uterine corpus with adnexa was performed during laparotomy. We evaluated the expression of aromatase cytochrome P450 (CYP 19) and 17β-hydroxysteroid dehydrogenase (17β HSD) by employing immunohistochemistry. RESULTS: Activity of 17β-HSD and CYP19 was demonstrated in the cytoplasm of stromal cells of postmenopausal ovaries, epithelium cells coating the ovaries, vascular endothelial cells, and epithelial inclusion cysts. However, overall expression of both 17β-HSD and CYP 19 decreased with time after menopause. CONCLUSION: Demonstration of the activity of the key enzymes of ovarian steroidogenesis, CYP 19 and 17β-HSD, confirms steroidogenic activity in the ovaries of postmenopausal women. Nevertheless, ovarian steroidogenic activity decreases with time, and its significant decrease occurs 10 years after menopause

Why are western diet and western lifestyle pro-inflammatory risk factors of celiac disease?

The prevalence of celiac disease increased in recent years. In addition to the genetic and immunological factors, it appears that environmental determinants are also involved in the pathophysiology of celiac disease. Gastrointestinal infections impact the development of celiac disease. Current research does not directly confirm the protective effect of natural childbirth and breastfeeding on celiac disease. However, it seems that in genetically predisposed children, the amount of gluten introduced into the diet may have an impact on celiac disease development. Also western lifestyle, including western dietary patterns high in fat, sugar, and gliadin, potentially may increase the risk of celiac disease due to changes in intestinal microbiota, intestinal permeability, or mucosal inflammation. Further research is needed to expand the knowledge of the relationship between environmental factors and the development of celiac disease to define evidence-based preventive interventions against the development of celiac disease. The manuscript summarizes current knowledge on factors predisposing to the development of celiac disease including factors associated with the western lifestyle

Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins.

Mitochondria are organelles with their own genomes, but they rely on the import of nuclear-encoded proteins that are translated by cytosolic ribosomes. Therefore, it is important to understand whether failures in the mitochondrial uptake of these nuclear-encoded proteins can cause proteotoxic stress and identify response mechanisms that may counteract it. Here, we report that upon impairments in mitochondrial protein import, high-risk precursor and immature forms of mitochondrial proteins form aberrant deposits in the cytosol. These deposits then cause further cytosolic accumulation and consequently aggregation of other mitochondrial proteins and disease-related proteins, including α-synuclein and amyloid β. This aggregation triggers a cytosolic protein homeostasis imbalance that is accompanied by specific molecular chaperone responses at both the transcriptomic and protein levels. Altogether, our results provide evidence that mitochondrial dysfunction, specifically protein import defects, contributes to impairments in protein homeostasis, thus revealing a possible molecular mechanism by which mitochondria are involved in neurodegenerative diseases

The effect of sewage sludge and BAF inoculant on plant condition and yield as well as biochemical and microbial activity of soil in willow (Salix viminalis L.) culture as an energy crop

Excessive amounts of sewage sludge produced in sewage treatment plants along with the ban on its storage and dumping require rapid solutions to the problem of sewage sludge management. An example of a rational and environmentally viable method may be provided by its application in agriculture and environmental management. The optimal solution is to use sludge as a fertiliser for industrial plants, including energy crops, that is, those not used in food production. For environmental reasons it is essential to control soil quality and condition following sludge application. Analyses of the residual effect of sewage sludge and bacteria, actinobacteria, fungi microbial inoculant (BAF) on selected physiological parameters of plants and microbial activity of soil were conducted in the years 2013–2015 on experimental fields of the Poznan University of Life Sciences. The results indicate that the application of sewage sludge increased yields and improved selected photosynthesis activity and biometric traits of willow. Among the tested combinations the best results were obtained following the application of sewage sludge combined with the BAF medium microbial inoculant. Similar dependencies were observed when evaluating soil microbial activity