The Effect of Dietary Addition of a Synbiotic After Long-Term Starvation on Certain Biochemical Parameters and Liver Structure in Common Carp (Cyprinus Carpio L.)

The prolonged starvation has many effects on the physiological and morphological processes in fish and interferes them with the ability to absorb nutrients and caloric intake. The aim of present study was to investigate the effect of long-term starvation and posterior dietary administration of commercial synbiotic consisting fructoligosaccharide (FOS) which used in combination with Enterococcus, Lactobacillus, Bifidobacterium and Lactococcus spp. for evaluation on some blood biochemical parameters and histological characteristics of common carp liver. Experimental fish after 5 months starvation period were subjected to the following feeding protocols: continuous starvation until 60 day (ST), re-feeding (FS) with dry composed diet (Aqua 1032 Swim) and refeeding with composed diet and synbiotic (FSS) for the following 60 days. Blood samples were used for analysis of the following plasma parameters: total protein, albumin, globulin, urea, creatinine, cholesterol, AST, ALT, glucose and serum for thyroid hormones. Histology analyses were performed on the carp liver samples. During the experimental period, fasting and refeeding were influenced significant on studied biochemical parameters, except glucose and urea. Also, the statistically largest (P <0.001) difference was observed in albumin and cholesterol values after refeeding. Our results reveal the changes in values of biochemical parameters during long-term starvation and refeeding with synbiotic and indicate signs of structural alterations of the liver in common carp.

Noncoding RNAs Interactions in Hepatic Stellate Cells during Hepatic Fibrosis

Hepatic fibrosis is a reversible wound healing process following liver injury. Although this process is necessary for maintaining liver integrity, severe excessive extracellular matrix accumulation (ECM) could lead to permanent scar formation and destroy the liver structure. The activation of hepatic stellate cells (HSCs) is a key event in hepatic fibrosis. Previous studies show that most antifibrotic therapies focus on the apoptosis of HSCs and the prevention of HSC activation. Noncoding RNAs (ncRNAs) play a substantial role in HSC activation and are likely to be biomarkers or therapeutic targets for the treatment of hepatic fibrosis. This review summarizes and discusses the previously reported ncRNAs, including the microRNAs, long noncoding RNAs, and circular RNAs, highlighting their regulatory roles and interactions in the signaling pathways that regulate HSC activation in hepatic fibrosis.

Metabolic effects of ramipril and indapamide in hypertensive patients with non-alcoholic fatty liver disease

Objective. To assess the effects of combined antihypertensive therapy with ramipril and indapamide on insulin resistance, carbohydrate, lipid and purine metabolism, as well as the structure and function of the liver in hypertensive patients with non-alcoholic fatty liver disease (NAFLD).Design and methods. In a pre-post study, we included 30 patients with hypertension (HTN) 1–2 degrees in combination with NAFLD (Fatty Liver Index (FLI) > 60) aged 45 to 65 years. Patients discontinued antihypertensive therapy 5–7 days before the initial examination. After that one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg) were prescribed along with the lifestyle and weight reduction recommendations (the Mediterranean type of diet, a decrease in calorie intake by 500–1000 kcal from baseline, and physical aerobic exercise at least 150 minutes per week). All patients underwent clinical examination, measurement of office blood pressure (BP), ambulatory BP monitoring (ABPM), anthropometric parameters, assessment of the visceral obesity index (VAI), anthropometric parameters, VAI, the degree of adipose tissue dysfunction (ATD), the percentage of visceral and subcutaneous fat by the bioelectrical impedance method. We also assessed lipid, carbohydrate, purine metabolism and the structural and functional state of the liver before and after the treatment.Results. After 24-week therapy with a fixed combination of ramipril and indapamide (average dosage of 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively) HTN patients with NAFLD achieved target BP. There was a decrease in both office systolic BP (SBP) (p < 0,001) and office diastolic BP (DBP) (p = 0,007) in 100 % of patients, as well as in ABPM indices. We observed a decrease in waist and hip circumferences (p ≤ 0,001 and p ≤ 0,001, respectively), the proportion of subcutaneous (p = 0,0134) and visceral (p = 0,002) fat. The number of patients with normal ATD increased (p = 0,030), while the proportion of patients with dysfunction decreased (p = 0,039). There was also a significant increase in high-density lipoprotein cholesterol (p = 0,027) and a decrease in insulin resistance (p = 0,002) and metabolic index (p = 0,030). We also found an improvement in carbohydrate metabolism with no change in purine metabolism. There was a favorable effect on the liver structure and function, and the number of patients with high alaninaminotransferase > 40 U/L decreased (5 (16,7 %) vs 0, p = 0,026).Conclusions. Twenty-fourweek treatment with a fixed combination of ramipril and indapamide, together with recommendations for lifestyle changes and weight loss, led to a significant decrease in BP levels, the severity of insulin resistance, and visceral obesity. In addition, the treatment had a beneficial effect on the parameters of carbohydrate and lipid metabolism, as well as liver structure and function (decreased severity of steatosis and fibrosis).

A novel minimally invasive OFM technique with orthotopic transplantation of hUC-MSCs and in vivo monitoring of liver metabolic microenvironment in liver fibrosis treatment

Background Mesenchymal stromal cells (MSCs) transplantation showed promising therapeutic results in liver fibrosis. However, efficient cell delivery method is urgently needed and the therapeutic mechanism remains unclear. This study focused on developing a minimally invasive open-flow microperfusion (OFM) technique, which combined orthotopic transplantation of human umbilical cord-derived (hUC)-MSCs to liver and in vivo monitoring of liver microenvironment in mice with CCl4-induced liver fibrosis. Methods The therapeutic potential of OFM route was evaluated by comparing OFM with intravenous (IV) injection route in terms of hUC-MSCs engraftment at the fibrosis liver, liver histopathological features, liver function and fibrotic markers expression after hUC-MSCs administration. OFM was also applied to sample liver interstitial fluid in vivo, and subsequent metabolomic analysis was performed to investigate metabolic changes in liver microenvironment. Results Compared with IV route, OFM route caused more hUC-MSCs accumulation in the liver and was more effective in improving the remodeling of liver structure and reducing collagen deposition in fibrotic liver. OFM transplantation of hUC-MSCs reduced blood ALT, AST, ALP and TBIL levels and increased ALB levels, to a greater extent than IV route. And OFM route appeared to have a more pronounced effect on ameliorating the CCl4-induced up-regulation of the fibrotic markers, such as α-SMA, collagen I and TGF-β. In vivo monitoring of liver microenvironment demonstrated the metabolic perturbations induced by pathological condition and treatment intervention. Two metabolites and eight metabolic pathways, which were most likely to be associated with the liver fibrosis progression, were regulated by hUC-MSCs administration. Conclusion The results demonstrated that the novel OFM technique would be useful for hUC-MSCs transplantation in liver fibrosis treatment and for monitoring of the liver metabolic microenvironment to explore the underlying therapeutic mechanisms.

STUDY OF GILL, KIDNEY AND LIVER STRUCTURE OF Pangasius hypophthalmus IN THE TANJUNG KUDU LAKE AND SAIL RIVERS, RIAU PROVINCE

Environmental condition and water quality in general may affects the health status of fish and it represents in the structure of fish organs such as the gill, kidney, and liver. To understand the structure of the gill, kidney, and liver of Pangasius pangasius that live in the Tanjung Kudu Lake (good water quality) and in the Sail River that has been polluted, a study has been conducted from November to December 2020. Twelve fishes (6 fishes/river) were analyzed. The tissue was formalin-fixed and processed through alcohol series, paraffin-embedded, 5m sliced and Hematoxylin-Eosin stained. The histological samples were then studied using a binocular microscope Olympus CX 21. The abnormality level of the tissue was categorized using the Histopathological Alteration Indeks (HAI). Results showed that the fish tissues from both study sites indicate light abnormality signs such as hyperplasia, hypertrophy, and lifted epithelia. The HAI was 2 for fish from the Tanjung Kudu Lake and 3 for the fish from the Sail River. This index indicates that the abnormality may be cured as the water quality improved.

A Novel Minimally Invasive OFM Technique Combined Orthotopic Transplantation of hUC-MSCs with in vivo Monitoring of Liver Metabolic Microenvironment in Liver Fibrosis Treatment

Background Mesenchymal stromal cells (MSCs) transplantation showed promising therapeutic results in liver fibrosis. However, efficient cell delivery method is urgently needed and the therapeutic mechanism remains unclear. This study focused on developing a minimally invasive open-flow microperfusion (OFM) technique, which combined orthotopic transplantation of human umbilical cord-derived (hUC)-MSCs to liver and in vivo monitoring of liver microenvironment in mice with CCl4-induced liver fibrosis. Methods The therapeutic potential of OFM route was evaluated by comparing OFM with intravenous (IV) injection route in terms of hUC-MSCs engraftment at the fibrosis liver, liver histopathological features, liver function and fibrotic markers expression after hUC-MSCs administration. OFM was also used to sample liver interstitial fluid in vivo, following metabolomic analysis was performed to investigate metabolic changes in liver microenvironment. Results OFM route caused more hUC-MSCs accumulation in the liver and was more effective in improving the remodeling of liver structure and reducing collagen deposition in fibrotic liver than IV. OFM transplantation of hUC-MSCs reduced blood ALT and AST levels, to a greater extent than IV route. And OFM route appeared to have a more pronounced effect on ameliorating the CCl4-induced up-regulation of the fibrotic markers, such as α-SMA, collagen I and TGF-β. In vivo monitoring of liver microenvironment demonstrated the metabolic perturbations induced by pathological condition and treatment intervention. Two metabolites and eight metabolic pathways which were most likely to be associated with the liver fibrosis progression, were regulated by hUC-MSCs administration. Conclusion The results demonstrated that the novel OFM technique would be useful for hUC-MSCs transplantation in liver fibrosis treatment and for monitoring of the liver metabolic microenvironment to explore the underlying therapeutic mechanisms.

Growth, Chemical Composition, Histology and Antioxidant Genes of Atlantic Salmon (Salmo salar) Fed Whole or Pre-Processed Nannochloropsis oceanica and Tetraselmis sp.

New sustainable feed ingredients are a necessity for the salmon aquaculture industry. In this study, we examined the effect of pre-extrusion processing of two microalgae, Nannochloropsis oceanica and Tetraselmis sp., on the growth, fatty acid content in the flesh and health of Atlantic salmon. The fish were fed one of the following five diets for nine weeks: (1) CO: a fish meal-based control (basal) diet, (2) NU: a Nannochloropsis diet, (3) NE: a pre-extruded Nannochloropsis diet, (4) TU: a Tetraselmis diet, and (5) TE: a pre-extruded Tetraselmis diet. The algae-incorporated diets contained 30% of the respective microalgae. Our results showed that the best growth performance was achieved by the CO diet, followed by the NE diets. Feeding of unprocessed Nannochloropsis and Tetraselmis resulted in a significant reduction in enterocyte vacuolization compared to the CO feeding. A significant effect of processing was noted in the fillet fatty acid content, the intestine and liver structure and the expression of selected genes in the liver. The expression of antioxidant genes in both the liver and intestine, and the accumulation of different fatty acids in the fillet and liver of the extruded algae-fed groups, warrants further investigation. In conclusion, based on the short-term study, 30% inclusion of the microalgae Nannochloropsis oceanica and Tetraselmis sp. can be considered in Atlantic salmon feeds.

Considerations regarding liver current pathology

This work presents reasoning about liver pathology. Liver pathology is an area of interest due to the growing number of medical cases worldwide. The factors associated with the appearance of this pathology are those that relate to individual lifestyle. Liver pathology studies are performed up to the biomolecular level, involving cytochrome P450 2E1 (CYP2E1). With a normal liver, subject to aging and the aforementioned risk factors, there are changes in liver structure, which often can lead to changes arising from nonalcoholic hepatic steatosis (NASH). Under certain circumstances this degenerates into chronic hepatitis, which often goes undiagnosed and this can lead to liver cirrhosis. Due to gradual changes in the liver, medical interventions are often delayed. Importantly, structural analysis of microscopically processed liver fragments will reveal changes in all structural elements of the liver, from lipid loading in hepatic steatosis to inflammatory, necrotic, destructive, fibrotic changes in liver cirrhosis, including somewhat similar changes in types of chronic hepatitis. The presented images and the described structural changes in the liver are an important criterion for liver damage, including preclinical pathology.