Life Profile Research Articles

Safety and efficacy of resmetirom in metabolic dysfunction-associated steatohepatitis (MASH): a systemic review and meta-analysis

Metabolic dysfunction-associated steatohepatitis (MASH) affects nearly 38% of the population, potentially progressing to cirrhosis and cancer. Lifestyle changes remain the cornerstone of management, but adherence is challenging, prompting the exploration of therapeutic options. Resmetirom, targeting thyroid hormone receptors, regulates liver enzymes and fat metabolism, showing potential as a treatment for MASH. This systematic review and meta-analysis evaluates the safety of resmetirom in MASH patients. Three randomized controlled trials with adult participants were analyzed, sourced from PubMed and the Cochrane Library until April 2024. Participants received either resmetirom or placebo, and data on adverse effects and efficacy outcomes were extracted. Statistical analyses, including risk ratios (RRs) and confidence intervals (CI), were performed using Review Manager (version 5.4.1) with a random-effects model. The pooled RR for serious adverse events was 0.85 (95% CI: 0.63–1.14; P = 0.28), indicating no significant difference. However, diarrhea (RR = 1.82, 95% CI: 1.41–2.35; P < 0.001) and nausea (RR = 1.73, 95% CI: 1.31–2.28; P < 0.001) showed higher incidence. No significant differences were found for fatigue (RR = 1.19, 95% CI: 0.77–1.84; P = 0.43) or urinary tract infections (RR = 1.07, 95% CI: 0.76–1.52; P = 0.69). Liver fat content, lipid profiles, and liver enzymes also showed significant improvement in the resmetirom group. Low heterogeneity across most outcomes indicated consistent findings among the studies. While resmetirom demonstrates efficacy in improving lipid and liver profiles, its increased risk of diarrhea and nausea should be considered in therapeutic decisions.

Integrated miRNA-seq and functional analyses reveal the regulatory role of sha-miR-92a_L + 2R + 4 via targeting vegfaa in rainbow trout (Oncorhynchus mykiss) responding to acute hypoxia and reoxygenation stress

BackgroundHypoxia negatively affects the behavior, growth, reproduction and survival of fish, causing serious economic losses to aquaculture. Rainbow trout (Oncorhynchus mykiss), an important economic fish worldwide, belongs to a hypoxia-sensitive fish species, however, little is known about the regulatory mechanism of microRNAs (miRNAs) under hypoxia stress.ResultsRainbow trout were subjected to hypoxia stress for 3 h (H3h_L), 12 h (H12h_L), 24 h (H24h_L) and 3 h reoxygenation (R3h_L) to systemically evaluate the changes of miRNA expression profiles in liver, and functions of sha-miR-92a_L + 2R + 4 were investigated. We found 17, 144, 57 and 55 differentially expressed (DE) miRNAs in the H3h_L vs. control (N_L), H12h_L vs. N_L, H24h_L vs. N_L and R3h_L vs. N_L comparisons, respectively. Enrichment analysis revealed that the targets of DE miRNAs were significantly enriched in HIF signaling pathway, VEGF signaling pathway, FoxO signaling pathway and glycolysis/gluconeogenesis. Through miRNA-mRNA interaction and weighted gene co-expression network analysis (WGCNA), five key DE miRNAs (sha-miR-92a_L + 2R + 4, ssa-miR-128-3p, ssa-miR-101b-3p_R + 1, ola-miR-199a-5p_R + 2 and tni-miR-199_1ss18CG) were identified, which can target at least two hypoxia-responsive genes, such as vegfaa, ho, glut1a and junb. Functional analysis found that sha-miR-92a_L + 2R + 4 directly regulated vegfaa expression by targeting its 3′-UTR, overexpression of sha-miR-92a_L + 2R + 4 significantly decreased vegfaa expression in rainbow trout liver cells, while opposite results were obtained after transfection of sha-miR-92a_L + 2R + 4 inhibitor. Furthermore, overexpressed sha-miR-92a_L + 2R + 4 promoted rainbow trout liver cell proliferation and inhibited apoptosis.ConclusionThis study deepens our understanding of the crucial roles of miRNAs under hypoxia stress in rainbow trout. These results can contribute to devise strategies for improving rainbow trout survival rate and aquaculture production during hypoxia stress and help speeding up the selective breeding of hypoxia-tolerant rainbow trout.

Hepatoprotective Effects of Rheum turkestanicum Janisch on High-fat Diet-induced Non-alcoholic Fatty Liver Disease in Mice

Background: Consumption of a high-fat diet (HFD) is one of the main causes of nonalcoholic fatty liver disease (NAFLD), which is increasing due to lifestyle changes and is still an important global health issue. Despite the efforts, there is still no common treatment for this disease. Studies have shown that the root of Rheum turkestanicum Janisch has a hypolipidemic effect and a significant antioxidant effect on liver tissue in diabetic rats. However, no experimental study has been performed on the hepatoprotective effects of this herb on HFD-induced NAFLD have been proven. background: Consumption of a high-fat diet (HFD) is one of the main causes of non-alcoholic fatty liver disease (NAFLD), which is increasing due to lifestyle changes and is still an important global health issue. Despite the efforts, there is still no common treatment for this disease. Studies have shown that the root of Rheum turkestanicum Janisch has a hypolipidemic effect and a significant antioxidant effect on liver tissue in diabetic rats. However, no experimental study has been performed on which the hepatoprotective effects of this herb on HFD-induced NAFLD have been proven. Objective: This study aimed to evaluate the effect of Rheum turkestanicum Janisch extract (RTE) on HFD-induced NAFLD in BALB/c mice. Materials and Methods: The study was performed with two models of prevention and therapeutic effect of RTE. Serum biochemical markers, histopathology, oxidative stress indicators, and qRTPCR were measured to evaluate the effects of RTE on lipid metabolism disorders in mice feeding with HFD. Results: In the prevention model, compared to the HFD group, RTE treatment decreased the levels of glucose, triglyceride, and cholesterol and improved liver profile markers, oxidative stress, and expression of genes involved in lipid metabolism. Conclusion: The results of this study suggest that RTE has hepatoprotective effects against HFDinduced liver damage by reducing oxidative stress, lipogenesis, and increasing beta-oxidation of free fatty acids.

How the liver transcriptome and lipid composition influence the progression of nonalcoholic fatty liver disease to hepatocellular carcinoma in a murine model

The incidence of nonalcoholic fatty liver disease (NAFLD) has been steadily increasing in Western society in recent years and has been recognized as a risk factor for the development of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the progression from NAFLD to HCC are still unclear, despite the use of suitable mouse models. To identify the transcriptional and lipid profiles of livers from mice with NAFLD-HCC, we induced both NAFLD and NAFLD-HCC pathologies in C57BL/6J mice and performed RNA-sequencing (RNA-seq) and targeted lipidomic analysis. Our RNA-seq analysis revealed that the transcriptional signature of NAFLD in mice is characterized by changes in inflammatory response and fatty acid metabolism. Moreover, the signature of NAFLD-HCC is characterized by processes typically observed in cancer, such as epithelial to mesenchymal transition, angiogenesis and inflammatory responses. Furthermore, we found that the diet used in this study inhibited cholesterol synthesis in both models. The analysis of lipid composition also showed a significant impact of the provided diet. Therefore, our study supports the idea that a Western diet (WD) affects metabolic processes and hepatic lipid composition. Additionally, the combination of a WD with the administration of a carcinogen drives the progression from NAFLD to HCC.

Efficacy of ayurveda medications, Brahmi vati and Saraswatarista, in generalized anxiety disorder- a randomized controlled trial

BackgroundAyurvedic intervention (Brahmi Vati with Saraswatarista) is explored for their possible role in management of Generalized Anxiety Disorder (GAD), a common psychiatric disorder. ObjectiveThe objective of the study was to evaluate the efficacy of Brahmi Vati and Saraswatarista in GAD. MethodsStudy is a randomized controlled clinical trial. Patients (n = 50) of GAD (Diagnostic and Statistical Manual of Mental Disorders (DSM-5 criteria), 18–60 years of age, either sex participated in the study. Participants were randomly divided into two groups. Group A, received escitalopram 10 mg/day for first 10 days followed by 20 mg/day for next 50 days. Group B, received Ayurvedic intervention (Brahmi Vati 500 mg thrice a day (TID) and Saraswatarista 10 ml TID) for 60 days. Assessments were with clinical parameters like Hamilton Anxiety Rating Scale (HARS), GAD 7 scale (GAD 7), Beck Depression Inventory scale (BDI), Epworth sleepiness scale (ESS), Pittsburgh Sleep Quality Index (PSQI), WHO Quality of Life- BREF (WHOQOL-BREF), Clinical Global Improvement scale (CGI) and UKU-Side effect scale (UKU). These clinical assessments were measured on every 15th day during the intervention. Haemoglobin, liver function test (LFT), serum creatinine, serum urea were assessed before and after the study. ResultsStudy results indicate that both the groups were comparable in HARS, GAD7, BDI, WHOQOL-Bref and CGI-Severity. Group B was better in PSQI (standard mean difference = 0.87, 95% CI: 0.28, 1.43), ESS (standard mean difference = 1.42, 95% CI: 0.78, 2.02), CGI [global improvement (standard mean difference = 0.82, 95% CI: 0.23,1.28) and efficacy index (standard mean difference = 0.97, 95% CI: 0.37,1.54)] and had better adverse events profile (standard mean difference = 0.79, 95% CI: 0.21, 1.36). Both the groups had a good safety profile assessed through liver and renal profiles. ConclusionAyurveda interventions has additional advantages likes improvements in sleep profile, lesser adverse events and better global improvement in management of GAD.CTRI Registration Number is CTRI/2020/09/027750.

Dual inhibition of SGLT 1 and 2 alleviates intracellular sodium overload in uraemic cardiomyopathy

Abstract Background Chronic kidney disease (CKD) is a leading cause of mortality with the risk of developing cardiovascular disease higher than progression to kidney failure. The aetiology of uraemic cardiomyopathy is multifactorial and includes metabolic derangement. It was previously shown that elevated intracellular sodium (Nai) is causally linked to cardiac metabolic impairment and that targeting sodium homeostasis can reprogramme cardiac metabolism. Dual inhibition of sodium-glucose co-transporters (SGLT) 1 and 2 is an emerging therapy for CKD, however the impact on intracellular sodium and cardiac metabolism is yet to be elucidated. Purpose This study aimed to assess whether dual SGLT1/2 inhibitor sotagliflozin impacts cardiometabolic phenotype in CKD. Methods CKD was surgically induced by 5/6 nephrectomy in Wistar rats (n=46) for a period of 4 weeks, with chronic sotagliflozin treatment (5mg/kg) given for the last 3 weeks. Upon termination, hearts were Langendorff-perfused and studied using 31P and 23Na NMR spectroscopy (Sham n=7, CKD n=6, CKD+sotagliflozin n=5). To assess the cardiac-specific effect of the drug, acute sotagliflozin treatment (30mM) was delivered in the Langendorff perfusate to an additional group of CKD hearts (n=5). Furthermore, the effect of chronic sotagliflozin treatment on in vivo cardiac function (echocardiography n=23) and metabolic profile (1H NMR spectroscopy n=15) was assessed. Results CKD animals were characterized by significant renal dysfunction (2-fold increase in urea and creatinine vs sham, p<0.05), and HFpEF (EF(%) sham 82±2 vs CKD 80±1 p>0.05; diastolic dysfunction (E/A) sham 1.39±0.03 vs CKD 1.11±0.01, p=0.0018). Myocardial Nai was significantly elevated in CKD animals compared to sham controls (TQF 23Na 3.04±0.18 vs 2.01±0.32 arb units, p=0.03). Chronic sotagliflozin treatment didn’t impact renal or cardiac dysfunction. Neither chronic nor acute drug treatment impacted baseline CKD cardiac energetics (PCr/ATP sham 1.53±0.22, CKD 1.25±0.13, chronic 1.16±0.14, acute 1.18±0.13, p>0.05; ΔGATP (kJ/mol) sham -64±4, CKD -66±8, chronic -56±1, acute -59±3, p>0.05). However, both chronic and acute sotagliflozin treatment normalised the increased myocardial Nai (TQF 23Na chronic 2.17±0.12, acute 2.23±0.14 arb units, p>0.05 vs sham). Chronic drug dosing altered the systemic metabolic profile of CKD animals reducing the levels of circulating triglycerides and FFA (p<0.05) as well as altering metabolomic profile of liver, muscle and kidneys. Conclusion(s) We have shown that uraemic cardiomyopathy is characterised by HFpEF, elevated myocardial Nai and altered systemic metabolic profile. Both chronic and acute treatment with dual SGLT1/2 inhibitor sotagliflozin normalised myocardial Nai. The alleviation of Nai load could lead to improved cardiometabolic outcomes in CKD.

Comparative assessment of phenotypic markers in patients with chronic inflammation: Differences on Bifidobacterium concerning liver status.

The relationship between systemic lupus erythematosus (SLE) and low-grade metabolic inflammation (MI) with the microbiota is crucial for understanding the pathogenesis of these diseases and developing effective therapeutic interventions. In this context, it has been observed that the gut microbiota plays a key role in the immune regulation and inflammation contributing to the exacerbation through inflammatory mediators. This research aimed to describe similarities/differences in anthropometric, biochemical, inflammatory, and hepatic markers as well as to examine the putative role of gut microbiota concerning two inflammatory conditions: SLE and MI. Data were obtained from a cohort comprising adults with SLE and MI. Faecal samples were determined by 16S technique. Statistical analyses compared anthropometric and clinical variables, and LEfSe and MetagenomeSeq were used for metagenomic data. An interaction analysis was fitted to investigate associations of microbiota with fatty liver index (FLI) depending on the inflammatory condition. Participants with low-grade MI showed worse values in anthropometry and biochemicals compared with patients with SLE. The liver profile of patients with MI was unhealthier, while no relevant differences were found in most of the inflammatory markers between groups. LEfSe analysis revealed an overrepresentation of Bifidobacteriaceae family in SLE group. An interactive association between gut Bifidobacterium abundance and type of disease was identified for FLI values, suggesting an effect modification of the gut microbiota concerning liver markers depending on the inflammatory condition. This study found phenotypical and microbial similarities and disparities between these two inflammatory conditions, evidenced in clinical and hepatic markers, and showed the interactive interplay between gut Bifidobacterium and liver health (measured by FLI) that occur in a different manner depending on the type of inflammatory disease. These results underscore the importance of personalized approaches and individual microbiota in the screening of different inflammatory situations, considering unique hepatic and microbiota profiles.

Effect of ultrasound and enzymatic pre-treatments on the profile of bioactive peptides of beef liver hydrolysates

The use of meat by-products as a potential source of protein hydrolysates rich in bioactive peptides is of growing interest to valorise these products and improve their sustainable use. This study aimed to evaluate the effect of different pre-treatments (hydrolysis with pepsin, ultrasounds, and ultrasounds-assisted pepsin hydrolysis) on the peptide profile and bioactivity of beef liver hydrolysed with flavourzyme. The pre-treatments with pepsin increased the degree of hydrolysis and generation of free amino acids in the liver hydrolysates, whereas the subsequent hydrolysis with flavourzyme influenced the molecular weight distribution of the peptides. Samples pre-treated with pepsin and ultrasounds-assisted pepsin hydrolysates showed the highest values of antioxidant and inhibitory activity of ACE-I, ECE-I, DPP-IV, and neprilysin enzymes, and therefore these hydrolysates were characterised to obtain the bioactive peptide profiles. A total of 995 peptides were identified by tandem mass spectrometry in the most active fractions separated by reversed-phase liquid chromatography, and 20 of them were predicted as potentially responsible for the observed bioactivities and subsequently characterised by in silico tools. These results evidenced the potential of hydrolysis pre-treatments with pepsin and ultrasounds-assisted pepsin to obtain beef liver hydrolysates rich in bioactive peptides that could exert multifunctional bioactivities such as antioxidant, antihypertensive, and antidiabetic, while giving added value to this meat by-product.

The Development of a Novel Nanoherbal Passionfruit (Passiflora edulis) Leaves with Safety and Analgesic Effect

Passionfruit (Passiflora edulis) leaves are proven to contain flavonoids especially quercetin and showed a significant antinociceptive effect at acetic acid-induced wriggling. Modification of passionfruit leaf extract into nanoparticles can provide therapeutic effects precisely, quickly, and optimally. This study aimed to provide the method of preparation, and characterization of nanoherbal passionfruit leaves (NPL) and evaluate its safety profiles and analgesic effect. NPL was synthesized using ionic gelation methods, with 3 formula variations. Passionfruit leaf extract was dissolved using mixed solvents. The passionfruit leaves extract solution was suspended in Chitosan and dripped with sodium tripolyphosphate solution until nanoparticle formation. The characterization of the NPL study was evaluated by measuring the particle size, polydispersity index (PI), zeta potential, entrapment efficiency (EE), drug release, and transmission electron microscope (TEM) images. The safety profiles of NPL were then assessed in mice by acute and subchronic toxicity using OECD methods. The effectiveness of NPL as an analgesic was tested using an acetic acid test (visceral pain) in mice. We found the particle size of the NPL’s best formula (F2-NPL) obtained was 187.6 nm with polydispersity index 0.626 and zeta potential +31.2 mV. The entrapment efficiency of flavonoid content in NPL was 50.9 % and the flavonoid release for 3 h with 3 replications were 22.91, 27.88 and 25.27 % respectively. The morphology of the particles by TEM showed that the nanoparticles were circular shape. Safety evaluation in mice resulted in the LD50 of NPL being greater than 5000 mg/kg in the acute toxicity study and had no adverse effects on blood, liver, and renal profiles in the subchronic toxicity study. The NPL-200 group had better effectiveness as an analgesic (84.87 %) compared to NPL-50 (37.80 %) and NPL-100 (69.15 %). This finding indicates that the NPL is a safe and effective formula for enhancing analgesic effects. Thus, enables its applications for the treatment of various diseases related to analgesics and inflammation such as osteoarthritis. HIGHLIGHTS The development of traditional medicine continues to be improved, to obtain the availability of safe, high quality, efficacious traditional medicines that are scientifically tested and can be widely utilized both for self-treatment by the community and in health services It is known that the most widely reported flavonoid derivative contained in edulis leaves is quercetin. Quercetin has poor bioavailability, solubility, and stability, reducing its therapeutic effect. By creating nanoparticles, adjustments can be made to natural products including quercetin in flavonoids in order to maximize their activity, boost their bioavailability, solubility, and capacity to be swiftly absorbed in the body to deliver the best possible therapeutic effects In developing nanoherbal passionfruit leaves using the ionic galation method, several solvents were used. It is known that no chemical substance can be said to be completely safe. It is important to study the toxicity profile further to obtain safe traditional medicines. Nanoparticle formulation of passion fruit leaf extract can provide better pain inhibition effectiveness in mice GRAPHICAL ABSTRACT

Loss of Bicra/Gltscr1 leads to a defect in fetal liver macrophages responsible for erythrocyte maturation in mice.

GLTSCR1, a protein encoded by the Bicra gene, is a defining subunit of the SWI/SNF (also called mammalian BAF) chromatin remodeling subcomplex called GBAF/ncBAF. To determine the role of GLTSCR1 during mouse development, we generated a Bicra germline knockout mouse using CRISPR/Cas9. Mice with homozygous loss of Bicra were born at Mendelian ratios but were small, pale and died within 24 hours after birth. Histology indicated blood-related defects including defective erythroblastic islands and irregularly sized red blood cells. Gene expression profiling of fetal livers pinpointed a defect in liver resident macrophages involved in the last stage of erythrocyte maturation, resulting in accumulation of nucleated erythrocytes in Bicra-/- pups. Together, these results demonstrate that Bicra is critical for fetal liver macrophage function during development.

Liver and renal biochemical profiles of people with sickle cell disease in Africa: a systematic review and meta-analysis of case-control studies

BackgroundSickle cell disease (SCD) is a genetic blood disorder characterized by a painful vaso-occlusive crisis due to the sickling of red blood cells in capillaries. Complications often lead to liver and renal dysfunctions, contributing to morbidity and mortality, particularly for children under 5. This systematic review and meta-analysis aimed to evaluate the liver and renal functions of people with SCD (HbSS) compared to those without it (HbAA) in Africa.MethodsThe protocol was registered with PROSPERO (CRD42022346771). We searched PubMed, Embase, Web of Science, and Google Scholar using the keywords “liver function”, “renal function”, “sickle cell disease”, and “Africa” on 6th May 2023 for peer-reviewed articles with abstracts in English. We included case-control studies comparing SCD (HbSS) with controls without hemoglobinopathies (HbAA). We used the random-effect model to calculate the pooled average values for the blood tests of people with SCD in RStudio version 4.2.2.ResultsOverall, 17 articles were analyzed from five African countries involving 1312 people with SCD and 1558 controls. The pooled mean difference of liver enzymes aspartate transaminase (AST) was 8.62 (95% CI − 2.99–20.23, I2 = 97.0%, p < 0.01), alanine transaminase (ALT) 7.82 (95% CI − 0.16–15.80, I2 = 99%, p < 0.01) and alkaline phosphatase (ALP) − 2.54 (95% CI − 64.72 – 59.64, I2 = 99%, p < 0.01) compared to controls. The pooled mean difference for the renal biochemical profiles creatinine − 3.15 (95% CI − 15.02; 8.72, I2=99%, p < 0.01) with a funnel plot asymmetry of t = 1.09, df = 9, p = 0.3048 and sample estimates bias of 6.0409. The pooled mean difference for serum urea was − 0.57 (95% CI − 3.49; 2.36, I2 = 99%, p < 0.01), and the estimated glomerular filtration (eGFR) rate was 19.79 (95% CI 10.89–28.68 mL/min/1.73 m2, I2 = 87%, p < 0.01) compared to controls.ConclusionPeople with SCD have slightly elevated liver enzymes and estimated glomerular filtration rates compared to controls in Africa. With all the heterogeneity (I2) > 50%, there was substantial variation in the reported articles’ results.Systematic review registrationPROSPERO CRD42022346771

Adipokine/hepatokines profiling of fatty liver in adolescents and young adults: cross-sectional and prospective analyses of the BCAMS study.

The underlying connections between obesity and non-alcoholic fatty liver disease (NAFLD) are not fully understood. One potential link might be the imbalanced adipokines and hepatokines. We aimed to explore the associations between specific adipokines/hepatokines and NAFLD in Chinese youth and to determine how these biomarkers mediate the obesity-NAFLD relationship. We analyzed data from the 10-year follow-up visit of the Beijing Children and Adolescents Metabolic Syndrome (BCAMS) study (n = 509; mean age = 20.2years) for a comprehensive metabolic risk assessment, including liver ultrasound and plasma measurements of adiponectin, leptin, fibroblast growth factor 21 (FGF21), retinol-binding protein 4 (RBP4), and angiopoietin-like protein 8 (ANGPTL8). Longitudinal analysis was performed on a subgroup (n = 307), with complete baseline (mean age = 12.2years) and follow-up data. Mediation models assessed how obesity at baseline and follow-up influence NAFLD through these biomarkers. Participants with NAFLD exhibited a high prevalence of central obesity (90.9%). Both cross-sectional and prospective analyses identified increased RBP4, FGF21, leptin, and decreased adiponectin levels as significant predictors of NAFLD. More adipokine/hepatokine abnormalities were linked to higher NAFLD risk. Furthermore, ratios reflecting adipokine/hepatokine imbalances, including leptin/adiponectin, FGF21/adiponectin, and RBP4/adiponectin, demonstrated stepwise changes correlating with NAFLD severity (all p < 0.05). Mediation analysis indicated that these four adipokines/hepatokines accounted for approximately 72.4% of the central obesity-NAFLD relationship and 80.1% in the subgroup analysis using baseline childhood data. Dysregulated adipokines/hepatokines may explain the onset or progression of obesity-related NAFLD in youths. Higher RBP4, FGF21 and leptin, alongside lower adiponectin, could serve as early biomarkers for NAFLD.

Assessing Alcohol Genes Targets in Mouse Liver

Background: Alcohol is a risk factor for liver diseases. There is a correlation between alcohol consumption and fatty liver disease. Experiences have shown gene expression alteration in the liver following alcohol consumption. Since the molecular mechanism of connection between alcohol consumption and fatty liver disease needs a clear perspective, this study aims to explore the significant genes that are targeted by alcohol in the liver of mice.Methods: Gene expression profiles of mice livers fed with alcohol were retrieved from the Gene Expression Omnibus (GEO) database and compared with the control samples. Data are pre-evaluated with the GEO2R program, and the significant differentially expressed genes (DEGs) are analyzed via gene expression evaluations and regulatory network assessment. Results: Among the 25619 dysregulated genes, 78 significant DEGs were pointed out. Gene expression analysis showed that most extremely dysregulated genes are up-regulated and belong to the cytochrome P450 genes family. Finally, cytochrome P450 and glutathione S-transferase genes family, as well as hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 4, were introduced as the critical targeted genes.Conclusion: In conclusion, detoxification of xenobiotics, cellular metabolism and homeostasis, the pathogenesis of some liver diseases, synthesis of several prostaglandins and steroid hormones, and inflammation fibrosis in the liver are possibly associated with alcohol consumption.

Point-of-care biochemistry for primary healthcare in low-middle income countries: a qualitative inquiry

BackgroundAccess to essential diagnostics is crucial for primary healthcare (PHC) in low-and-middle income countries (LMICs). Many LMICs have invested in equipping PHC with point-of-care (PoC) diagnostics for infectious diseases, however there has been no similar investment to improve PHC capacities for clinical chemistry. The biochemistry gap is among the deterrents to universal health coverage.MethodsA social sciences project was conducted with the aim to understand the key PHC stakeholders’ insights on the pertinence of PoC biochemistry for PHC in LMICs. Data generation was conducted between July-November 2023 in Mongolia, Nigeria and Peru. Decision-makers in healthcare delivery, healthcare professionals, and patient and community advocates were engaged using a combination of sampling techniques. Unstructured individual and group conversations, and non-participant observation were conducted. Analysis involved an inductive line-by-line coding on printed transcripts, followed by a deductive coding and theme-by-theme analysis on digitized transcripts.ResultsFifteen, 51 and 20 informants from Mongolia, Nigeria and Peru, respectively, participated. Fifty-five of the 94 informants were female. Most informants considered that PoC biochemistry in PHC would be pertinent, from a clinical and a resources-saving perspective. Those households that currently bear the burden of referrals (i.e., the poor, the bedridden, the older adults) would benefit the most from the deployment of PoC biochemistry for essential biochemistry parameters. Improved access to PoC glycated hemoglobin (HbA1c), lipid, liver and kidney profile was perceived as helpful to inform clinicians’ decision-taking. The value of PoC biochemistry for the management of noncommunicable diseases (diabetes, hypertension) and infectious conditions (dengue, malaria, tuberculosis), to improve child health outcomes (severe dehydration in children with diarrhea and/or malnutrition) and to reduce preventable causes of death (dengue-related renal failure) was highlighted.ConclusionsPoC biochemistry holds potential to revert the impact that the biochemistry gap has for patient care in some LMICs’ PHC settings. PoC equipment for parameters such as HbA1c, urea, creatinine or electrolytes could enhance community-level management of preventable causes of mortality, improve service delivery for patients affected by locally-prevalent infectious conditions, and improve the psychosocial and economic wellbeing of patients facing the burden of referrals to remote biochemistry-equipped centers.Trial RegistrationNot applicable.

Re-evaluating the necessity of routine laboratory monitoring during isotretinoin therapy for acne.

In this letter, we discuss the topic of necessity of routine laboratory monitoring during isotretinoin treatment for acne. According to Park and colleagues, it is advisable to monitor the levels of triglycerides, alanine aminotransferase, and aspartate aminotransferase every 5 to 6 months. Additionally, the levels of total cholesterol and low-density lipoprotein should be checked within the first two months of treatment. Isotretinoin is a commonly prescribed agent mainly used to treat acne. Despite its high effectiveness, it necessitates regular monitoring of laboratory parameters due to its side effect profile. Currently, there remains a lack of consensus on the appropriate frequency for monitoring these parameters during treatment with isotretinoin. This letter will provide insight into this complex and controversial topic. Based on existing literature, we concluded that the incidence of changes in lipid and liver aminotransferase levels during isotretinoin treatment for acne was low and likely clinically insignificant. For generally healthy people, we recommend testing lipid and liver profiles once at baseline and a second time at the peak dosage. However, frequent testing might still be beneficial in certain populations of patients.

6448 Metabolic Profile and Adipose Tissue Distribution of Young Individuals with Turner Syndrome

Abstract Disclosure: V.M. Thomas: None. P.F. Backeljauw: Consulting Fee; Self; Novo Nordisk, Ascendis, Biomarin, Cavalry Biosciences, Upsher-Smith Laboratories, Tolmar. Speaker; Self; BioMarin, Ascendis.. A. Shah: None. I. Gutmark-Little: Research Investigator; Self; Novo Nordisk, Ascendis, OPKO. Introduction: Turner syndrome (TS) is the most common sex chromosome abnormality in females. Incidence of type 2 diabetes mellitus, hypertension, and dyslipidemia is high in TS. Current practice is to employ BMI as a proxy for adiposity. However, BMI is not an optimal tool due to the short stature observed in TS. Alternate methods such as the dual-energy x-ray absorptiometry (DXA) scan and bioelectrical impedance (BI) may provide more information about body composition. Objectives: The objective of this study is to assess alternative outpatient methods for body composition assessment, including adiposity in pediatric patients with TS. The secondary goal is to characterize the metabolic profile of pediatric subjects with TS compared to obese (BMI ≥95 th%ile) and lean controls (BMI: 5-85th%ile). Methods: This is a cross-sectional study. TS patients are on ≥50mcg transdermal estradiol equivalent replacement OR are self-menstruating. BI, DXA, metabolic markers, interleukin-6 (IL-6) &amp; C-reactive protein (CRP) were obtained in all 3 groups. Statistical analysis was conducted using SPSS software. Results: We present preliminary data on 15 TS, 12 obese, and 15 lean youth, aged 13-19 years. TS youth averages: Age 16.5±1.3 years; BMI 29.3±8.5 kg/m2 (z-score: 1.21±1.27). DXA visceral adiposity (DXA VA): 392±257 g; BI visceral fat (BI VF): 1300±750 cm². Elevated LDL-C&amp;gt;100 mg/dL was noted in n=5 (102-166). Elevated AST &amp;/or ALT &amp;gt;40 unit/L were found in 6 TS. 6 TS had elevated BI VF and DXA VA (&amp;gt;250g) with BMI z-score &amp;lt;2.0. Increased CRP &amp;/or IL-6 levels were noted in 4 TS (BMI z-score: 1.29-2.54), all of whom had primary ovarian failure. These 4 also had increased DXA VA (358-887 g), and BI VF (1500-2500 cm²) compared to the rest of the group. Obese youth averages: Age 16.7±1.83 years; BMI 38 kg/m2 (z-score: 2.26±0.3); DXA VA 674±226 g; BI VF 2300±390 cm². LDL-C&amp;gt;100 mg/dL noted in n=5 (102-121). AST&amp;ALT&amp;lt;35 units/L for all. Increased CRP &amp;/or IL-6 were noted in 4 study subjects (DXA VA: 474-718 g). All 4 had normal A1c, lipid, and liver profiles. Lean youth averages: Age 16.4±2.4 years, BMI 21.6 kg/m2 (z-score: 0.32±0.7); DXA VA 162±68 g; BI VF: 580±370 cm². LDL-C &amp;gt;100 mg/dL noted in n=3 (106-120); 1 subject had increased AST&amp;ALT &amp;gt;40 unit/L. All others had AST &amp; ALT&amp;lt;26 units/L. Elevated CRP/IL-6 was noted in 4 subjects, 1 of whom had increased DXA VA (367g). All subjects had normal HgA1c (≤5.6). Total mass, lean mass, and fat % from DXA and BI were compared (correlation analysis) for each subject and showed agreement throughout. Conclusion: Based on these preliminary data, BI may be a convenient and noninvasive tool to assess adiposity in the outpatient setting in TS. BI and DXA both detected increased visceral fat in TS subjects with normal BMI. BI could potentially identify TS individuals at risk for metabolic dysfunction. Further studies on larger patient numbers will be needed to confirm these preliminary findings. Presentation: 6/2/2024

The influence of feed additive “Activo” on the content of total lipids and their classes profile in liver and skeletal muscles of pigs

With an increase in meat consumption the requirements for its quality also rise. As pork is the second most popular meat in the world, producers of this product are trying to improve its quality. The purpose of our research was to determine the effect of the feed additive “Activo”, containing essential oils of cinnamon, rosemary and oregano, and chili pepper extract, on the total lipids content and their individual class profile in liver and skeletal muscles of pigs. The study was conducted on pigs of the large white breed, weighing 70 kg, divided on two groups, according to the piglets-analogues principle, which then were divided into control and experimental groups. Pigs of both groups received standard feed (SF) intended for this age group. Pigs of the experimental group received the feed additive “Activo” in an amount of 0.1 kg/t of feed in addition to SF. The duration period of experiment was 40 days. Samples of liver, longissimus dorsi, and latissimus dorsi muscle tissues were used as material for the study. The total lipid content was determined using gravimetric method, and individual lipid profile using thin-layer chromatography on silica gel plates. The study has shown that the total lipid content in the liver, long and broad back muscles of pigs of the experimental group was 1.66 and 1.95 (P≤0.001) and 1.26 (P≤0.05) times higher, respectively, than in animals of the control group. The relative cholesterol esters content in the liver lipids of the experimental group pigs was 1.9 (P≤0.001) times higher than in the control group. Instead, in the latissimus dorsi muscle, a lower content of triacylglycerols and a higher content of unesterified fatty acids (P≤0.05), esterified cholesterol (P≤0.05), and especially phospholipids (P≤0.001) were admitted. It was determined significant decrease of unesterified cholesterol content in the latissimus dorsi muscle (P≤0.001) and increase of phospholipids content (P≤0.001) under the effect of the researched feed additive.

Impact of Etonogestrel-releasing contraceptive implant use in cisgender women with Sickle cell disease

BackgroundSickle cell disease is a hereditary hemolytic anemia that exposes women to increased health risks especially in pregnancy, with serious implications for the woman and fetus. Acute pain episodes can occur multiple times per month and result in reduction of quality of life and disruption of her life. ObjectiveTo assess the clinical, including pain and metabolic parameters of women with sickle cell disease using etonogestrel-releasing contraceptive implants. MethodsWomen with sickle cell disease, aged 18–40 years, with reports of pain crises in the preceding 3 months were included and followed up for 12 months. Blood samples were collected to evaluate the blood count, reticulocytes, liver profile (alkaline phosphatase, gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin and its fractions), lipid profile, and lactate dehydrogenase levels before and 6 and 12 months after implant insertion. The following clinical variables were analyzed every 3 months: bleeding pattern, blood pressure, weight, body mass index, pain intensity (assessed using a visual analogic scale (VAS) from 0 to 10), and frequency of pain crises. ResultsTwenty-three women completed the study. There were no differences in laboratory variables between baseline and 6 and 12 months after implant insertion. Similarly, clinical variables did not differ, except for pain intensity (VAS pre-insertion = 8 vs. VAS 12 months post insertion = 4; p = 0.005) and frequency of pain crises (pre-insertion = 6 vs. 12 days/month post insertion = 0; p = 0.000). ConclusionsEtonogestrel-releasing contraceptive implants were associated with a reduction in the intensity and frequency of pain crises in women with sickle cell disease. Moreover, it was safety among these population due to no changes in laboratory parameters during the first 12 months of use.

Normal caloric intake with high-fat diet induces metabolic dysfunction-associated steatotic liver disease and dyslipidemia without obesity in rats

Excessive caloric intake and obesity due to high-fat (HFD) and high-disaccharide (HDD) diets have been recognized as major contributing factors to dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effect of HFD and HDD without excessive caloric intake is obscure. The aim of the study was to evaluate the effect of physiological caloric intake delivered through HFD and HDD on liver and lipid profiles. The study was performed on 6-week-old male and female (50/50%) Sprague Dawley rats, receiving either a standard (controls, n = 16), HFD (n = 14) or HDD (n = 14) chow. All groups received the same, standard daily calorie rations, titrated weekly to the age of growing rats, for 12 weeks. A panel of metabolic in vivo measurement were performed, followed by histological, biochemical and molecular biology assays on tissues harvested from sacrificed rats. There was no significant difference between the groups in body weight. In contrast to controls, HFD and HDD groups showed metabolic dysfunction-associated steatohepatitis (MASH) characterized by liver steatosis, inflammation, ballooning of hepatocytes and fibrosis. These changes were more pronounced in the HFD than in the HDD group. The HFD group showed significantly higher serum LDL than controls or HDD rats. Furthermore, the HFD group had higher liver protein levels of low-density lipoprotein receptor (LDLR) but lower plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) than the controls or HDD group. There were no differences between sexes in evaluated parameters. The excessive caloric intake and obesity are not prerequisites for the development of MASH and dyslipidemia in rats. The liver changes induced by the HFD and HDD diets exhibit differences in severity, as well as in the expression patterns of LDLR and PCSK9. Notably, these effects are independent of the sex of the rats.

Relation between liver, kidney function, and lipid profile in glycaemic control among type 2 diabetic patients in Al Baha City

Relation between liver, kidney function, and lipid profile in glycaemic control among type 2 diabetic patients in Al Baha City