Life Profile Research Articles

Flavonoid-Rich Trianthema decandra Ameliorates Cognitive Dysfunction in the Hyperglycemic Rats.

The present study was aimed at the evaluation of neuroprotective ability of methanolic extract of Trianthema decandra (METD) against hyperglycemia-related cognitive impairment in rats. The extract of T. decandra was standardized by TLC and HPTLC methods. To verify the identity and purity of isolated compounds, they were segregated and characterized using various techniques, including UV-visible spectrophotometry, FT-IR, H-NMR, and Mass spectroscopy. α-Amylase and α-glucosidase inhibition property of the extracts were assessed in-vitro. The screening of the neuroprotective effects of METD in hyperglycemic rats was done utilizing Morri's water (MWM) and elevated plus maze (EPM) model, as well as acetylcholinesterase (AChE) activity. The extracts of Trianthema decandra and its chemical constituents, namely quercetin and phytol, demonstrated a significant protective effect on enzymes like α-amylase and α-glucosidase. Methanol and hydroalcoholic extracts have shown the strongest inhibitory activity followed by chloroform extract. Quercetin and phytol were associated with the methanolic and chloroform extracts which were identified using TLC and HPTLC techniques. During the thirty days of the study, the induction of diabetes in the rats exhibited persistent hyperglycemia, hyperlipidemia, higher escape latency during training trials and reduced time spent in target quadrant in probe trial in Morris water maze test, and increased escape latency in EPM task. Regimen of METD (200 and 400 mg/kg) in the diabetic rats reduced the glucose levels in blood, lipid, and liver profile and showed positive results on Morri's water and elevated plus maze tasks. During the investigation, it was determined that Trianthema decandra extracts and the chemical constituent's quercetin and phytol in it had anti-diabetic and neuroprotective activities.

Differential Regulation of Male-Hormones-Related Enhancers Revealed by Chromatin Accessibility and Transcriptional Profiles in Pig Liver.

Surgical castration can effectively avoid boar taint and improve pork quality by removing the synthesis of androstenone in the testis, thereby reducing its deposition in adipose tissue. The expression of genes involved in testis-derived hormone metabolism was altered following surgical castration, but the upstream regulatory factors and underlying mechanism remain unclear. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics in liver tissue of castrated and intact full-sibling Yorkshire pigs. First, we identified 897 differentially expressed genes and 6864 differential accessible regions (DARs) using RNA- and ATAC-seq. By integrating the RNA- and ATAC-seq results, 227 genes were identified, and a significant positive correlation was revealed between differential gene expression and the ATAC-seq signal. We constructed a transcription factor regulatory network after motif analysis of DARs and identified a candidate transcription factor (TF) SP1 that targeted the HSD3B1 gene, which was responsible for the metabolism of androstenone. Subsequently, we annotated DARs by incorporating H3K27ac ChIP-seq data, marking 2234 typical enhancers and 245 super enhancers involved in the regulation of all testis-derived hormones. Among these, four typical enhancers associated with HSD3B1 were identified. Furthermore, an in-depth investigation was conducted on the androstenone-related enhancers, and an androstenone-related mutation was identified in a newfound candidatetypical enhancer (andEN) with dual-luciferase assays. These findings provide further insights into how enhancers function as links between phenotypic and non-coding area variations. The discovery of upstream TF and enhancers of HSD3B1 contributes to understanding the regulatory networks of androstenone metabolism and provides an important foundation for improving pork quality.

Abstract 759: Soy protein diet changes metabolic profile in liver of 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary tumors in obese zucker rats

Abstract Obesity is associated with the risk of certain types of cancers development including breast cancer. Previously, we reported that obesity increased mammary tumor development using obese Zucker rat model. Several studies have shown the health benefit of soy protein consumption. However, the effects of soy protein diet on liver of mammary tumor for oxidative stress and DNA reaction is less known. We used DMBA induced-mammary tumor model to investigate the effects of soy protein diet on pro-oxidative environment and oxidative DNA modification in liver of obese DMBA mammary tumors rats. Female obese zucker rats (n=45) were either fed casein as control (OC; n=20) or soy protein isolate (OS; n=25), received DMBA (65mg/kg BW) at the age 50 days and sacrificed 20 weeks later. We used HPLC-ECD, HPLC-UV and LC-MS techniques for liver metabolic analysis. Comparing liver of OS vs. OC, soy protein 1) decreased the level of Methionine (P<0.02), increased 2) free reduced Homocysteine (P<0.02), 3) S-Adenosylmethionine (SAM, P<0.03), 4) S-Adenosyhomocysteine (SAH, P<0.001) and 5) 5methyl-Cytosine (5mC, P<0.03). Also, soy protein decreased (P<0.003) level of free oxidized Glutathione (GSSG), increased (P<0.02) GSH/GSSG oxidative stress ratio, without any changes a level of free reduced Glutathione (GSH), followed decrease (P<0.04) in liver DNA level of 8-OH-Guanosine (8-OH-G) and level (P<0.02) of 5hmethyl-Cytosine (5hmC). Our results shows soy protein diet capable change liver metabolism: a. Modify a methylation status by increasing levels of SAM (universal methyl group donor) following global liver DNA hypermethylation (5mC), and SAH (methylases inhibitor); b. Alleviate level of oxidative stress in liver by decreasing level of GSSG (not active glutathione), increasing GSH/GSSG ratio (antioxidative capacities), following lower ROS liver DNA damages by decrease levels of 8-OH-G and 5hmC. In conclusion, using obese DMBA-induced mammary tumor Zucker rat model, soy diet making a complex and significantly modification of metabolic conditions in liver affecting both methionine cycle and transsulfuration metabolic pathways. Citation Format: Reza Hakkak, Stepan Melnyk. Soy protein diet changes metabolic profile in liver of 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary tumors in obese zucker rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 759.

Induction of Experimental Peri-Implantitis with Strains Selected from the Human Oral Microbiome.

Peri-implantitis (PI), the most widespread condition in the oral cavity, affects patients globally; thus, advanced research in both in vitro and in vivo studies is required. This study aimed to develop peri-implantitis in the rat model by oral contamination with bacteria responsible for PI in humans. The study was carried out in three stages: the extraction of the maxillary first molar to reproduce the human edentation, the mounting of the implant, and finally, the contamination of the device by gavage with Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus oralis. The hematological examinations showed statistically significant increases for WBCs (white blood cells), Hb (hemoglobin), RBCs (red blood cells), MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration), and PLTs (platelets), but especially for the level of neutrophils and lymphocytes, and the systemic immunoinflammatory index completed the picture related to the inflammatory response triggered as a result of the activity of microorganisms pathogens on oral tissues. By examining the liver and kidney profile, we hypothesized that peri-implantitis is associated with systemic diseases, and the histopathological examination showed peri-implantitis lesions characterized by a marked inflammatory infiltrate with numerous neutrophils and lymphocytes. By corroborating all the results, we successfully developed a rat peri-implantitis model using a mixed bacterial infection through the oral gavage technique.

Abstract 7444: Hepatotoxicity from L-asparaginase is associated with lipid changes in a mouse model

Abstract L-asparaginase (Calaspargase-pegol, PEG) is currently an important component of acute lymphoblastic leukemia (ALL) treatment in children, adolescents, and young adults. Despite its high efficacy, toxicities including hepatotoxicity limit its use. Asparaginase-associated hepatotoxicity is often associated with obesity and fatty liver, highlighting lipid metabolism as a potential contributor to fatty liver. Therefore, we performed lipidomic analyses of plasma and liver from control and obese mice treated with one dose of PEG, to determine whether specific lipid moieties or classes may be associated with the hepatotoxicity produced by PEG. Control and obese 18-week-old male C57Bl6/J mice were treated with one dose of 3000 IU/kg PEG or vehicle (n = 6 per group). Hepatotoxicity was assessed one week later by liver histopathology and plasma alanine transaminase (ALT) and albumin levels. Liver and plasma lipidomic profiles were also analyzed by UHPLC-QTRAP-MS/MS. One week post Veh vs. PEG were compared using two-sided, unpaired t-tests. PEG increased liver steatosis scores in both control (Veh: 0.5±0.2, PEG: 3.7±0.3, p<0.001) and obese mice (Veh: 4.0±0.6, PEG: 6.7±0.2, p<0.01). While ALT levels did not show a clear pattern with PEG treatment, albumin level decreased in both control (Veh: 3.6±0.1, PEG: 2.7±0.2, p<0.01) and obese mice (Veh: 4.1±0.2, PEG: 2.8±0.1, p<0.01). Lipidomics analysis showed that plasma lipids generally decreased with PEG treatment in control (not shown) and more significantly in obese mice (Phosphatidylcholines [PC]: Veh 3000.0±381.1, PEG 507.2±71.5, p<0.001; Phosphatidylethanolamine [PE]: Veh 604.7±128.1, PEG 295.3±75.0, p<0.001; triglycerides [TG]: Veh 649.7±89.7, PEG 150.6±49.3, p<0.001). Similar patterns were observed in control (not shown) and obese livers for PC (Veh 11.1±0.8, PEG 5.7±0.8, p<0.001) and PE (Veh 6.7±0.8, PEG 3.5±0.5, p<0.001), whereas liver TG increased with treatment (Veh 220.1±113.5, PEG 586.6±113.4, p<0.001). Interestingly, there were strong negative correlations between steatosis score and liver PC (r2=0.46, p<0.001) and PE (r2=0.62, p<0.001). As low PC has been shown to induce fatty liver, this finding implies that PEG might induce steatosis via reduction in PC and its precursor, PE. Future work will investigate the mechanisms by which PEG reduces liver PE and PC levels, and whether this is causally related to steatosis and hepatotoxicity. Citation Format: Veronica Ruiz-Torres, Jennifer J. Chia, Michael Cohen, Jia Tan, Praveen Bandaru, Austin Brown, Van Huynh, Etan Orgel, Steven D. Mittelman. Hepatotoxicity from L-asparaginase is associated with lipid changes in a mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7444.

Long-Term Effect of Maternal Antioxidant Supplementation on the Lipid Profile of the Progeny According to the Sow's Parity Number.

Pig feeding prior to the extensive fattening phase might affect the final lipid profile and product quality. This study evaluates how maternal supplementation with vitamin E (VITE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg), or combined administration (VE + HXT) affects the piglet's plasma and tissues' fatty acid profiles and lipid stability according to the sow's parity number (PN), as well as the possible changes to the lipid profile after extensive feeding. The sows' PN affected the total fatty acid profile of plasma, muscle, and liver of piglets, with lower Δ-9 and Δ-6 desaturase indices but higher Δ-5 in those from primiparous (P) than multiparous (M) sows. Dietary VITE was more effective at decreasing C16:0 and saturated fatty acids in the muscle of piglets born from M than P sows, and modified the liver phospholipids in a different way. Sows' supplementation with HXT increased C18:2n-6 in triglycerides and polyunsaturated fatty acids (PUFA) in muscle phospholipids. In the liver, HXT supplementation also increased free-PUFA and free-n-3 fatty acids. However, lipid oxidation of piglets' tissues was not affected by the antioxidant supplementation, and it was higher in the livers of piglets born from M sows. The fatty acid profile in the muscle of pigs after extensive feeding was not affected by the PN, but it was by the sows' antioxidant supplementation, with positive effects on quality by both compounds.

Effect of dengue infection on liver profile and hematological parameters

Dengue fever is endemic in Sri Lanka. Liver damage is common in dengue fever. Understanding the pattern change of the liver profile and haematological parameters is crucial for managing dengue patients and minimising liver damage. The purpose of this study was to determine the pattern change in liver profile and the haematological parameters of dengue patients. Sixty apparently healthy volunteers and 169 acute dengue patients aged 20 or older had their blood samples examined. Liver enzymes, albumin, protein, bilirubin, white blood cell count, platelet count, haematocrit, and haemoglobin were measured. There was an increase in aspartate aminotransferase (105.6 IU/L), alanine aminotransferase (82.6 IU/L), and gamma-glutamyl transferase (68.9 IU/L), which were 3.4, 3.9, and 3.2-fold higher, respectively, than those of the control group, suggesting liver injury. Eighty-four percent of patients had raised levels of aspartate aminotransferase, and 74% of patients had elevated levels of alanine aminotransferase, indicating the prominence of aspartate aminotransferase over alanine aminotransferase. The presence of a positive correlation between the levels of aspartate aminotransferase and alanine aminotransferase indicates that the elevation of enzymes is primarily due to a single cause, liver injury. White blood cells and platelet counts were significantly lower. Platelet count demonstrated a negative correlation with both haematocrit and haemoglobin in dengue patients. In conclusion, aspartate aminotransferase was identified as the most significant marker of dengue-associated liver injury, followed by alanine aminotransferase. Low platelet and white blood cell counts were the major unfavourable changes in dengue patients' haematological characteristics.

Feasibility of replacing fish oil with sunflower oil on the growth, body composition, fatty acid profile, antioxidant activity, stress response, and blood biomarkers of Labeo rohita.

A 90-day study was conducted to investigate the effects of substituting sunflower oil (SFO) for fish oil (FO) on various parameters in Labeo rohita (initial weight 18.21 ± 0.22 g). Five experimental diets with different levels of SFO (up to 7%) substitution for FO (0%, 25%, 50%, 75%, and 100%) were formulated, ensuring equal levels of nitrogen and lipids. The results indicated that even with 100% substitution of SFO with FO, there were no significant differences (P>0.05) were observed in growth performance. The survival rate (SR), hepato-somatic index (HSI), and viscero-somatic index (VSI) as well as whole-body composition were also nonsignificant by SFO substitution. However, the fatty acid profiles in both muscle and liver were influenced (P<0.05) by dietary substitution. Saturated fats (SFA) decreased, while monounsaturated fats (MUFA), and linoleic acid (LA) increased (P<0.05). On the other hand, the contribution of linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) decreased (P<0.05) as the amount of SFO in the diet increased. Hematology parameters, including red blood cells (RBCs), hemoglobin (Hb), and hematocrit (Hct), were not affected. Globulin (GLO) levels decreased significantly (P<0.05), while alanine transaminase (ALT) and aspartate transaminase (AST) activity showed nonsignificant increases (P>0.05). Total protein (TP) increased (P<0.05) at 100% SFO inclusion in the diet, and albumin (ALB) levels increased (P<0.05) at 75% and 100% SFO inclusion in the diet. Cholesterol (CHOL), triacylglycerol (TG), and high-density lipids (HDL) were not significantly affected (P>0.05), while low-density lipids (LDL) were significantly increased (P<0.05) compared to the control group. Cortisol (CORT) and glucose (GLU) levels showed nonsignificant (P>0.05) changes. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities in the liver and serum were not significantly (P>0.05) affected, while malondialdehyde (MDA) status was significantly (P<0.05) reduced. In conclusion, the fatty acid profile of the muscle and liver of fish was modified by the diets, and FO can be substituted with SFO up to 100% for L. rohita, which is beneficial for growth and immunity while marinating the lipid contents in fish. Our study revealed that fully replacing fish oil with SFO shows promise in fully replacing FO without compromising the growth and overall health status of the fish.

Reorganization of 3D genome architecture provides insights into pathogenesis of early fatty liver disease in laying hens

BackgroundFatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate. Three-dimensional (3D) chromatin architecture takes part in disease processing by regulating transcriptional reprogramming. The study is carried out to investigate the alterations of hepatic 3D genome and H3K27ac profiling in early fatty liver (FLS) and reveal their effect on hepatic transcriptional reprogramming in laying hens.ResultsResults show that FLS model is constructed with obvious phenotypes including hepatic visible lipid deposition as well as higher total triglyceride and cholesterol in serum. A/B compartment switching, topologically associating domain (TAD) and chromatin loop changes are identified by high-throughput/resolution chromosome conformation capture (HiC) technology. Targeted genes of these alternations in hepatic 3D genome organization significantly enrich pathways related to lipid metabolism and hepatic damage. H3K27ac differential peaks and differential expression genes (DEGs) identified through RNA-seq analysis are also enriched in these pathways. Notably, certain DEGs are found to correspond with changes in 3D chromatin structure and H3K27ac binding in their promoters. DNA motif analysis reveals that candidate transcription factors are implicated in regulating transcriptional reprogramming. Furthermore, disturbed folate metabolism is observed, as evidenced by lower folate levels and altered enzyme expression.ConclusionOur findings establish a link between transcriptional reprogramming changes and 3D chromatin structure variations during early FLS formation, which provides candidate transcription factors and folate as targets for FLS prevention or treatment.

Protocolo diagnóstico de la hepatopatía crónica

Chronic liver disease is usually paucisymptomatic until the complications of liver failure and/or portal hypertension appear. In most cases, the diagnostic suspicion usually begins with abnormalities on the liver profile and/or a finding on imaging tests. The etiological diagnosis is broad, with the most frequent causes being metabolic dysfunction-associated liver disease, viral liver disease, and alcohol-related liver disease. A medical history and physical examination are the basis for guiding the diagnostic process, which must be supported by additional analytical and radiological tests. This etiologic evaluation must always be performed alongside an assessment of liver disease severity through an estimation of the degree of fibrosis and the presence of clinically significant portal hypertension. Currently, both of these are preferably estimated in a non-invasive manner. This protocol aims to summarize the fundamental keys to the diagnostic process in the case of suspected chronic liver disease.

Impact of dietary and herbal supplements on global health of adult volunteers

Abstract The safety and efficacy of multivitamin-multimineral-multiherbal (MVMH) supplementation is in regular debate but should be studied in detail before recommendation. The purpose of the study was to evaluate whether MVMH supplementation affects the physical and mental performance of individuals taking these, as well as to ascertain its safety, doing so through blood, kidney and liver profiles. In this Cross over cohort study, we enrolled 30 healthy volunteers and established their anthropometric, stress, anxiety and depression levels before and after 30 days of the study. Their kidney function test, liver function test and blood profile results were also analysed to determine overall health effects of the supplement and assess its safety. Parametric data was examined via Paired T test, followed by One Way ANOVA, Non-parametric data is presented as percentage and analysed by applying Paired Sample Wilcoxon Signal Rank Test followed by Friedman ANOVA test. All the volunteers were in good health, had no change in medical state. No serious adverse event was reported during the study and after the completion of study. Treatment with MVMH tablets had shown very significant (p &lt;0.01) increase in the level of globulin, uric acid (p &lt;0.05), hemoglobin, and hematocrit levels (p &lt;0.05), BMI and body weight (p &lt;0.05). There was significant (p &lt;0.05) improvement in symptoms of anxiety, depression and stress. The daily intake of MVMH supplements in the form of a tablet once per day improved global health of individuals, along with improvement in mental performance without any significant adverse impact on the body. Based on the results, we recommend that MVMH tablets may be taken once per day for 30 days to improve the physical and mental health of individuals.

Long-Term Supplementation of Royal Jelly (Raydel®) Improves Zebrafish Growth, Embryo Production and Survivability, Blood Lipid Profile and Functionality of Vital Organs: A 72-Weeks' Consumption Study.

Royal jelly is a honeybee product with substantial pharmacological and health promotional activities. Nevertheless, the health implications associated with the prolonged dietary supplementation of royal jelly have yet to be elucidated extensively. Herein, 72 weeks of dietary supplementation of royal jelly at 5% and 10% (w/w) were investigated to assess the impact on zebrafish survivability, body weight, liver, testis, ovary functionality, and blood lipid profile. The results revealed no adverse effect of 72 weeks of royal jelly supplementation on zebrafish survivability. Conversely, a noteworthy enhancement in the zebrafish body weight was observed in royal-jelly-supplemented zebrafish in a concentration-dependent manner [5% and 10% (w/w)]. Interestingly, female zebrafish were found to be more biased, with a significant 17% (p < 0.001) and 23% (p < 0.001) higher body weight enhancement after 72 weeks of consumption of 5% and 10% (w/w) royal jelly, compared to the male zebrafish. The histological outcome revealed no sign of hepatotoxicity; moreover, diminished reactive oxygen species (ROS) and apoptosis were observed in the hepatic tissue of the royal-jelly-supplemented group. Consistent with the histological outcomes, the liver function biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), exhibited a significant decrease of 1.9-fold (p = 0.006) and 1.4-fold (p = 0.003) in zebrafish supplemented with royal jelly compared to those on a normal diet (ND) and zebrafish given supplements. Also, no sign of ovary and testis-related toxicity was observed in the royal-jelly-supplemented group during the 72-week period. Furthermore, the 10% (w/w) royal-jelly-consuming zebrafish exhibited a notable 2.1-fold increase (p = 0.018) in egg-laying ability compared to the ND-supplemented zebrafish. The 10% (w/w) royal jelly supplementation also effectively maintained the blood lipid profile by curtailing serum triglycerides (TG) and elevating high-density lipoprotein cholesterol (HDL-C). Conclusively, royal jelly dietary supplementation for a prolonged time found royal jelly to be safe to consume, to efficiently improve hepatic function, reproduction, and sexual health, and to augment the serum HDL-C level.

Bioinformatic analysis and construction of competitive endogenous RNA network reveals protective effect of Jiangtang Sanhao Formula on the liver of diabetic mice

IntroductionJiangtang Sanhao Formula (JTSHF), composed of Panax ginseng, Atractylodes macrocephala, Coptis chinensis, Salvia miltiorrhiza and several other herbs, is a traditional Chinese medicine formula commonly used to treat type 2 diabetes. This compound shows significant clinical efficacy in the treatment of diabetic, however, its target and pharmacological mechanism are still unclear. The present study explored the therapeutic effect of JTSHF on diabetic mice and conducted RNA sequencing to investigate the potential mechanism. MethodsThe T2DM mice model was established using a high-fat diet combined with an intraperitoneal injection of low-dose STZ. Fasting blood glucose (FBG), serum insulin, glucose tolerance, and blood lipids in mice from different groups were examined. Then the effects of JTSHF on oxidative stress and liver histopathology in diabetic mice were observed. Next, transcriptome analysis was performed to identify differentially expressed genes (DEG), which were validated using real-time quantitative PCR (RT-qPCR). By using pathway enrichment analysis, we identified several key pathways which are essential in the JTSHF effect on T2DM. Finally, we constructed ceRNA network to illustrate the regulatory effect of JTSHF on transcriptional profile in diabetic liver. ResultsJTSHF reduced FBG level and blood lipid contents, ameliorated glucose tolerance and improved insulin sensitivity in diabetic mice. It also showed protective effects on fatty livers induced by high-fat diet and diabetes. For the first time, we revealed that JTSHF exerts anti-T2DM role in the liver of diabetic mice, which is associated with multiple molecular targets and signaling pathways. Enrichment analysis and treatment-based mRNA-ncRNA-miRNA ceRNA networks revealed that JTSHF might exerts therapeutic effect by modulating lipid metabolism. DiscussionOur research found that JTSHF exerts anti-T2DM effect by affecting multiple pathways. Among these, lipid metabolism and oxidative stress might be involved. The present study provided novel insights for the mechanism of JTSHF, and the differentially expressed genes identified can be potential therapeutic targets in the treatment of T2DM in future.

High-Fat Diet-Induced Decreased Circulating Bile Acids Contribute to Obesity Associated with Gut Microbiota in Mice.

The altered circulating bile acids (BAs) modulate gut microbiota, energy metabolism and various physiological functions. BA profiles in liver, serum, ileum and feces of HFD-fed mice were analyzed with normal chow diet (NCD)-fed mice after 16-week feeding. Furthermore, gut microbiota was analyzed and its correlation analysis with BA was performed. The result showed that long-term HFD feeding significantly decreased hepatic and serum BA levels, mainly attributed to the inhibition of hepatic BA synthesis and the reduced reabsorption efficiency of BAs in enterohepatic circulation. It also significantly impaired glucose and lipid homeostasis and gut microbiota in mice. We found significantly higher bile salt hydrolase activity in ileal microbes and a higher ratio of free BAs to conjugated BA content in ileal contents in HFD groups compared with NCD group mice, which might account for the activated intestinal farnesoid X receptor signaling on liver BA synthesis inhibition and reduced ileal reabsorption. The decreased circulating BAs were associated with the dysregulation of the lipid metabolism according to the decreased TGR5 signaling in the ileum and BAT. In addition, it is astonishing to find extremely high percentages of taurocholate and 12-OH BAs in liver and serum BA profiles of both groups, which was mainly attributed to the high substrate selectivity for 12-OH BAs of the intestinal BAs transporter during the ileal reabsorption of enterohepatic circulation. This study revealed a significant effect of long-term HFD feeding on the decreased circulating BA pool in mice, which impaired lipid homeostasis and gut microbiota, and collectively resulted in metabolic disorders and obesity.

Hypoglycemic Activity and Safety Assessment of Pediococcus acidilactici Strain DNH16 in Experimental Type 2 Diabetes Mellitus Rats Induced with Streptozotocin

BACKGROUND: Type 2 diabetes mellitus (T2DM) cases tend to rise throughout the year in all parts of the world. The α-glucosidase inhibitors are frequently used to both prevent and treat T2DM. This α-glucosidase inhibitor activity is seen in some probiotic species, and a certain strain of Pediococcus acidilactici exhibits promising characteristics as an α-glucosidase inhibitor. This study was conducted to assess the hypoglycemic activity and safety of P. acidilactici strain DNH16 (PADNH16) in experimental rats with T2DM induced by streptozotocin.METHODS: The experiment was conducted in vivo using Wistar rats. Acarbose was employed as a positive control, and Lactobacillus casei was used as a comparative. For 24 days, post-prandial blood glucose levels were assessed every 3 days, followed by serum biochemical levels measurement of liver, kidney, and lipid profiles. The pancreas was histopathologically examined utilizing the Hematoxyline-Eosin staining procedure.RESULTS: Administration of PADNH16 to T2DM rats lowered post-prandial blood glucose levels and gave hypoglycemic benefits comparable to acarbose and commercial probiotics. PADNH16 dosing did not affect serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), urea, or creatinine levels, showing that PADNH16 was not hazardous to liver or kidney function. The lipid profile assessment revealed that the values, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, were comparable to the control group. The pancreatic histopathology revealed that injection of PADNH16 caused no alterations to pancreatic β cells.CONCLUSION: P. acidilactici isolate DNH16 has a hypoglycemic effect on T2DM rats, but does not affect liver function enzymes, kidneys, lipid profiles and does not provide significant changes in pancreatic β cells.KEYWORDS: diabetes mellitus, inhibitor α-glucosidase, Pediococcus acidilactici strain DNH16

Alterations in the liver profile and other markers of asymptomatic patients who attend routine examinations in an urban area of Lima, Peru

Introducción: las enzimas y marcadores del perfil hepático permiten evaluar la funcionalidad y condición del hígado. Sus elevaciones pueden ser silentes y con cierta prevalencia en muchos adultos. Objetivo: determinar las principales alteraciones en el hepatograma en pacientes que acuden a consulta médica de rutina. Metodología: estudio descriptivo, prospectivo y transversal realizado a partir de resultados de laboratorio de historias clínicas de 364 pacientes de todas las edades y ambos sexos pertenecientes a un policlínico del distrito de Villa el Salvador, Perú desde enero de 2021 a julio de 2022. Las variables fueron: edad, sexo, valores de transaminasa glutámico pirúvica (TGP), transaminasa glutámico oxalacética (TGO), bilirrubina directa, indirecta y total, albúmina, globulinas y fosfatasa alcalina (FA). Resultados: en el promedio total de la muestra, la TGP fue alta (51,05 U/L), así como la bilirrubina total (1,50 mg/dL) y la FA (135,84 U/L). La TGP fue alta en hombres (54,92 U/L) y mujeres (48,86 U/L). La TGO fue normal en mujeres y alta en hombres (48,24 U/L). La bilirrubina indirecta fue alta en hombres (1,33 mg/dL). La FA fue más alta en ambos sexos (143,28 U/L en hombres y 126,38 en mujeres). Según grupo etario, los valores de TGO fueron más altos en el grupo de edad igual o mayor a 40 años (49,99 U/L). Los valores de TGP fueron elevados en ambos sexos (55,96 U/L en hombres y 50,90 U/L en mujeres), así como en la bilirrubina total, la que fue más alta en el grupo de edad igual o mayor a 40 años (2,03 mg/dL). La bilirrubina indirecta, albúmina y FA fueron normales en el grupo de edad igual o menor de 39 años, pero fueron elevadas en el grupo de edad igual o mayor a 40 años (1,13 mg/dL, 5,77 gr/dL y 147,95 U/L, respectivamente). Conclusiones: existen alteraciones en el perfil hepático en pacientes asintomáticos en la muestra estudiada. A pesar de no ser elevaciones significativamente grandes, se recomienda identificar y tratar las posibles causas que pudieran desencadenar dichas elevaciones, así como la realización de más estudios similares a nivel nacional para caracterizar el perfil hepático de nuestra población.

MgO Nanoparticle Synthesis, Chemical Delivery in Rat Model Induced Lung Injury

Acute lung injury is a disorder of acute inflammation that causes disruption of the lung endothelial and epithelial barriers. Acute Respiratory Distress Syndrome or ARDS is a diffuse inflammatory lung process that frequently manifests in critically ill patients, with an estimated incidence of 3 million people a year. Clinically, ARDS is manifested by bilateral or diffuse radiographic infiltrates, hypoxemia, decreased lung compliance, and increased ventilatory dead space. The histological manifestation of ARDS is diffuse alveolar damage as defined by epithelial injury, hyaline membrane formation and alveolar flooding with proteinaceous fluid, increase alveolar surface area and frequently neutrophilic inflammation. The animal model correlate to ARDS as an acute lung injury (ALI). Models were employed to test potential new therapeutic interventions and to investigate under-lying mechanistic pathways that lead to diffuse lung injury. In this study cage cigarette smoke model was used for an acute lung injury. For that purpose, thirty (30) young albino healthy rats were used, and their duration of trial was 21 days. Each group was given an oral drug administration containing MgO-150mg/kg, MgO-300mg/kg BW for treatment and diet schedule in young albino rats of male sex for the experimental procedure of 0 to 21 days. Mean body weight, BALF, lipid profile, liver profile and lung histology were assessed. Results revealed that MgO nanoparticles exhibited antioxidant capacity at dosages of 300mg/kg, and 150mg/kg. This formulation of selected nanoparticles at high dose exhibited an acute lung injury and antioxidant effects as compared to low dose extract. Additionally, transcriptional factors revealed up-regulation at high dose in contrast to the low dose extract in lung injury treated groups.

IgG4-Related Disease and Monoclonal Gammopathy: Case Report

Background: IgG4-related disease (IgG4-RD) is a progressive, chronic, atypical presenting clinical entity characterized by an elevated serum IgG4 level, leading to an immune-mediated fibroinflammatory condition affecting various organs.Case Summary: We present the case of a patient with clinical manifestations compatible with chronic pancreatitis due to the time of evolution. Physical examination revealed submaxillary, axillary, and inguinal lymphadenopathy and pain on abdominal palpation. Laboratory tests showed eosinophilia and a hepatocellular pattern in the liver profile. Immunofixation showed a monoclonal IgG lambda band with IgG4 values of 1183 mg/dl. To confirm the diagnosis of autoimmune chronic pancreatitis associated with IgG4-related sclerosing cholangitis, imaging tests were performed, which showed intrahepatic and extrahepatic cholestasis associated with pancreatic parenchymal alterations compatible with this entity. Subsequently, upon initiating glucocorticoid therapy, the patient evolved favorably. Conclusion: ER-IgG4 is a rare condition that causes inflammation and scarring in various organs. It is hard to diagnose and often mistaken for other diseases. The pancreas and biliary tract are frequently affected.

IgG4-Related Disease and Monoclonal Gammopathy: Case Report

Background: IgG4-related disease (IgG4-RD) is a progressive, chronic, atypical presenting clinical entity characterized by an elevated serum IgG4 level, leading to an immune-mediated fibroinflammatory condition affecting various organs. Case Summary: We present the case of a patient with clinical manifestations compatible with chronic pancreatitis due to the time of evolution. Physical examination revealed submaxillary, axillary, and inguinal lymphadenopathy and pain on abdominal palpation. Laboratory tests showed eosinophilia and a hepatocellular pattern in the liver profile. Immunofixation showed a monoclonal IgG lambda band with IgG4 values of 1183 mg/dl. To confirm the diagnosis of autoimmune chronic pancreatitis associated with IgG4-related sclerosing cholangitis, imaging tests were performed, which showed intrahepatic and extrahepatic cholestasis associated with pancreatic parenchymal alterations compatible with this entity. Subsequently, upon initiating glucocorticoid therapy, the patient evolved favorably. Conclusion: ER-IgG4 is a rare condition that causes inflammation and scarring in various organs. It is hard to diagnose and often mistaken for other diseases. The pancreas and biliary tract are frequently affected.

Quantitative proteomics study of carnosine effect in an animal model of Western diet-induced nonalcoholic fatty liver disease.

The nonalcoholic fatty liver disease (NAFLD), which is closely related to westernized dietary (WD) patterns, displays a rising epidemiological and economic burden. Since there is no pharmacological therapy approved for this disease, mechanistic studies are warranted. In this work, we investigated the action of carnosine (CAR), a natural dipeptide with several protection roles against oxidative stress in the liver of NAFLD rats. NAFLD was induced byWD-richsugars and fat, verifying the histological evidence of steatosis. As intraperitoneal administration of CAR reversed liver steatosis, the protein profiles of NAFLD liver and CAR NAFLD liver were evaluated by label-free proteomics approach. A total of 2531 proteins were identified and the 230 and 276 were significantly up- and downregulated, respectively, by CAR treatment of NAFLD rats and involved in fundamental pathways such as oxidative stress and lipid metabolism. Perilipin 2 and apolipoprotein E, components of the plasma membrane of vesicle, resulted in highly downregulated in the CAR-treated NAFLD liver. The advanced bioanalytical approach demonstrated the efficacy of CAR in overcoming the main symptoms of NAFLD, ameliorating the steatosis in the liver.