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The liver has a high regenerative potential that is dependent on many factors, in particular adenosine monophosphate kinase signaling, however, long-term alteration, such as daily alcohol consumption, turns regeneration into a chronic disease such as fibrosis, the end stage of which is cirrhosis. Hepatic extracellular matrix proteins are important triggers of enhanced stellate cell function during the progression of liver fibrosis. The experiments were performed on Wistar rats divided into four groups: control group; doxorubicin injection group (1.25 mg/kg); chronic alcohol hepatitis group; injection of doxorubicin during alcoholic hepatitis group, where we studied the total concentration of glycosaminoglycans, concentration of heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, free oxyproline and sialic acids in the liver tissue homogenate. Cells with Mallory-Denk bodies were present in the liver of rats from the alcohol hepatitis group, which consisted of tangled balls of intermediate filaments and showed eosinophilia in the cytoplasm of degenerative hepatocytes. There were also necrotic changes in cells. Sinusoidal capillaries were locally dilated. In the central sections of the liver lobules of rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the central veins were expanded, their endothelium was thinned. Sinusoidal capillaries were locally expanded, there were no blood cells in their lumens. The nuclei of the vast majority of hepatocytes were in a state of karyopyknosis, karyorrhexis, and karyolysis. Mallory-Denk bodies were present in the cytoplasm of cells. Administration of doxorubicin to animals with chronic alcoholic hepatitis leads to an increase in the total concentration of glycosaminoglycans, the concentration of chondroitin sulfates, a decrease in the heparin-heparan fraction of glycosaminoglycans and no changes in concentration of the keratan-dermatan fraction in the liver of rats compared to the control group. In the group of rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the concentrations of total glycosaminoglycans, heparin-heparan fraction, and chondroitin fraction significantly increased, and the content of the keratan-dermatan fraction of glycosaminoglycans significantly decreased compared to animals with chronic alcoholic hepatitis. In rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the content of free oxyproline decreased by 1.25 times, sialic acids – by 1.36 times, compared to the group of animals with chronic alcoholic hepatitis. Administration of ethanol or doxorubicin in combination with ethanol to rats causes morphological changes in the liver that are characteristic of chronic alcoholic hepatitis. Administration of doxorubicin to rats leads to degenerative morphological changes in the liver lobules. The administration of doxorubicin prevents alcohol-induced collagenolysis and the breakdown of glycoproteins, but increases the breakdown of proteoglycans due to an increase in the content of chondroitin and heparin-heparan fractions.

Metformin is an old drug, of plant origin, primarily used in the treatment of type 2 diabetes. The main mechanism of its action is mediated through adenosine monophosphate (AMP) kinase. Though the main action of metformin is to inhibit hepatic gluconeogenesis, it is also known to increase insulin sensitivity and is used in the treatment of obesity and polycystic ovarian disease. Its varied actions on coronavirus infections, by inhibiting virus entry, preventing cytokine storm, boosting immunity by altering the gut microbiota, and decreasing virulence by inducing autophagy makes it an ideal candidate for treating coronavirus disease-2019 (COVID-19). The only serious side effect of metformin is lactic acidosis, confined to a few patients. The drug is already approved by the US Food and Drug Administration (FDA) and thus repurposing it in COVID-19 patients may be beneficial. Metformin is a drug, approved by FDA for treating diabetes mellitus with very few side effects. It is inexpensive and is known to exhibit anti-COVID-19 actions. It has also proven to be effective in treating PCOS and obesity. Thus, it has all the potential to treat COVID-19.

The liver has a high regenerative potential that is dependent on many factors, in particular adenosine monophosphate kinase signaling, however, long-term alteration, such as daily alcohol consumption, turns regeneration into a chronic disease such as fibrosis, the end stage of which is cirrhosis. Hepatic extracellular matrix proteins are important triggers of enhanced stellate cell function during the progression of liver fibrosis. The experiments were performed on Wistar rats divided into four groups: control group; doxorubicin injection group (1.25mg/kg); chronic alcohol hepatitis group; injection of doxorubicin during alcoholic hepatitisgroup, where we studied the total concentration of glycosaminoglycans, concentration of heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, free oxyproline and sialic acids in the liver tissue homogenate. Cells with Mallory-Denk bodies were present in the liver of rats from the alcohol hepatitis group, which consisted of tangled balls of intermediate filaments and showed eosinophilia in the cytoplasm of degenerative hepatocytes. There were also necrotic changes in cells. Sinusoidal capillaries were locally dilated. In the central sections of the liver lobules of rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the central veins were expanded, their endothelium was thinned. Sinusoidal capillaries were locally expanded, there were no blood cells in their lumens. The nuclei of the vast majority of hepatocytes were in a state of karyopyknosis, karyorrhexis, and karyolysis. Mallory-Denk bodies were present in the cytoplasm of cells. Administration of doxorubicin to animals with chronic alcoholic hepatitis leads to an increase in the total concentration of glycosaminoglycans, the concentration of chondroitin sulfates, a decrease in the heparin-heparan fraction of glycosaminoglycans and no changes in concentration of the keratan-dermatan fraction in the liver of rats compared to the control group. In the group of rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the concentrations of total glycosaminoglycans, heparinheparan fraction, and chondroitin fraction significantly increased, and the content of the keratan-dermatan fraction of glycosaminoglycans significantly decreased compared to animals with chronic alcoholic hepatitis. In rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the content of free oxyproline decreased by 1.25 times, sialic acids – by 1.36 times, compared to the group of animals with chronic alcoholic hepatitis. Administration of ethanol or doxorubicin in combination with ethanol to rats causes morphological changes in the liver that are characteristic of chronic alcoholic hepatitis. Administration of doxorubicin to rats leads to degenerative morphological changes in the liver lobules. The administration of doxorubicin prevents alcohol-induced collagenolysis and the breakdown of glycoproteins, but increases the breakdown of proteoglycans due to an increase in the content of chondroitin and heparin-heparan fractions [ABSTRACT FROM AUTHOR]

Resveratrol butyrate esters (RBEs), which are novel resveratrol-synthesized derivatives, exhibit increased biological activity. This study elucidated the effect of RBEs on fat metabolism and their anti-obesity characteristics. Their molecular mechanism was investigated in the 3T3-L1 murine preadipocyte cells and adipocytes. RBE doses of < 2 μM did not induce a significant change in the viability of 3T3-L1 adipocytes. After RBEs treatment, intracellular lipid droplet accumulation in 3T3-L1 adipocytes was stimulated by methylisobutylxanthine, dexamethasone, and insulin-containing medium. However, a significant dose-dependent reduction in intracellular lipid levels was observed. The mRNA levels of two adipogenic transcription factors (peroxisome proliferator-activated receptor [PPAR] and CCAAT/enhancer-binding proteins [C/EBP]) and lipogenic proteins (fatty acid-binding protein 4 [FABP4] and fatty acid synthase [FAS]) were significantly attenuated by RBE treatment in both MDI-stimulated and differentiated 3T3-L1 adipocytes. Moreover, the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) also dramatically increased in the MDI + RBE-treated group compared to that in the MDI + vehicle-treated group. Collectively, our study provides strong evidence that RBEs inhibit adipogenesis by regulating adipogenic protein expression and increasing the p-AMPK/AMPK ratio. Future studies will be conducted on animal models to validate the application of RBEs as a functional food ingredient in improving human health. [ABSTRACT FROM AUTHOR]

Insulin resistance and hyperinsulinemia play a key role in type 1 endometrial cancer pathogenesis. Most of these cancers develop on a background of overweight or type 2 diabetes mellitus (T2DM). One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways. Many epidemiological studies on diabetic patients show potential preventative role of metformin in endometrial cancer patients, but data regarding its therapeutic role is still limited. So far, most of attention has been paid to the concept of metformin use in fertility sparing treatment of early-stage cancer. Another investigated alternative is its application in patients with primary advanced or recurrent disease. In this review we present the latest data on clinical use of metformin in endometrial cancer patients and potential underlying mechanisms of its activity. Finally, we present some most important clinical information regarding metformin efficacy in other gynaecological malignancies, mainly breast and ovarian cancer. [ABSTRACT FROM AUTHOR]

Glycogen content and contraction strongly regulate glycogen synthase (GS) activity, and the aim of the present study was to explore their effects and interaction on GS phosphorylation and kinetic properties. Glycogen content in rat epitrochlearis muscles was manipulated in vivo. After manipulation, incubated muscles with normal glycogen [NG; 210.9 ± 7.1 mmol/kg dry weight (dw)1, low glycogen (LG; 108.1 ± 4.5 mmol/kg dw), and high glycogen (HG; 482.7 ± 42.1 mmol/kg dw) were contracted or rested before the studies of GS kinetic properties and GS phosphorylation (using phospho-specific antibodies). LG decreased and HG increased GS Km, for UDP-glucose (LG: 0.27 ± 0.02 < NG: 0.71 ± 0.06 < HG: 1.11 ± 0.12 mM; P < 0.001). In addition, GS fractional activity inversely correlated with glycogen content (R = -0.70; P < 0.001; n = 44). Contraction decreased Km for UDP-glucose (LG: 0.14 ± 0.01 NG: 0.16 ± 0.01

The article discusses the results of a study on the tissue-specific effect of a high-fat diet on adiponectin and related enzyme expression. The characterization of obesity by accumulation of lipids is explained and a definition of the term adiponectin is given. The correlation between serum adiponectin levels and adipose tissue weight is also elaborated.

Background: Evidence suggests CaHMB may impact muscle mass and/or strength in older adults, yet no long-term studies have compared its effectiveness in sedentary and resistance training conditions. The purpose of this study was to evaluate the effects of 24 weeks of CaHMB supplementation and resistance training (3 d wk(-1)) or CaHMB supplementation only in ≥65 yr old adults., Methods: This double-blinded, placebo-controlled, trial occurred in two phases under ad libitum conditions. Phase I consisted of two non-exercise groups: (a) placebo and (b) 3 g CaHMB consumed twice daily. Phase II consisted of two resistance exercise groups: (a) placebo and resistance exercise and (b) 3 g CaHMB consumed twice daily and resistance exercise (RE). Strength and functionality were assessed in both phases with isokinetic leg extension and flexion at 60°·s(-1) and 180°·s(-1) (LE60, LF60, LE180, LF180), hand grip strength (HG) and get-up-and-go (GUG). Dual X-Ray Absorptiometry (DXA) was used to measure arm, leg, and total body lean mass (LM) as well as total fat mass (FM). Muscle Quality was measured for arm (MQ(HG)=HG/arm LM) and Leg (MQ60=LE60/leg LM) (MQ180=LE180/leg LM)., Results: At 24 weeks of Phase I, change in LE60 (+8.8%) and MQ180 (+20.8%) for CaHMB was significantly (p<0.05) greater than that for placebo group. Additionally, only CaHMB showed significant (p<0.05) improvements in total LM (2.2%), leg LM (2.1%), and LE180 (+17.3%), though no treatment effect was observed. Phase II demonstrated that RE significantly improved total LM (4.3%), LE60 (22.8%), LE180 (21.4%), HG (9.8%), and GUG (10.2%) with no difference between treatment groups. At week 24, only CaHMB group significantly improved FM (-3.8%) and MQHG (7.3%); however there was no treatment main effect for these variables., Conclusion: CaHMB improved strength and MQ without RE. Further, RE is an effective intervention for improving all measures of body composition and functionality., (© 2013. Published by Elsevier Inc. All rights reserved.)

Berberine (BBR) is a natural alkaloid isolated from the Coptis Chinensis. While this plant has been used in Ayurvedic and Chinese medicine for more than 2500 years, interest in its effects in metabolic and cardiovascular disease has been growing in the Western world in the last decade. Many papers have been published in these years reporting beneficial effects in carbohydrate and lipid metabolism, endothelial function and the cardiovascular system. In this review, we report a detailed analysis of the scientific literature regarding this topic, describing the effects and the underlying mechanisms of BBR on carbohydrate and lipid metabolism, endothelial function and the cardiovascular system.