Aminotransferase Levels Research Articles

Serum autotaxin positively associates with hypertension in postmenopausal women: a single center study in China

Aim: Autotaxin is an adipokine involved in metabolic disorders. The aim of the current study was to evaluate serum autotaxin levels in hypertensive postmenopausal women and establish a relationship between autotaxin and other comorbidities in this special group. Methods: This single-center study included postmenopausal women who received annual health examinations at the First Affiliated Hospital, College of Medicine, Zhejiang University in Zhejiang, China. The metabolic and demographic characteristics of the subjects, including age, sex, height, weight, blood pressure, and biochemical indices, were collected. The serum autotaxin level was measured via ELISA. The Kolmogorov-Smirnov test, Student's t test, Mann–Whitney U test, χ 2 test, receiver operating characteristic (ROC) curve analysis, Spearman correlation analysis and multivariate logistic regression analysis were adopted for statistical analysis. Results: This pilot observational study included 25 hypertensive postmenopausal women and 25 age-matched normotensive controls. Hypertensive patients presented significant metabolic disturbances with greater comorbidities such as nonalcoholic fatty liver disease, obesity, overweight, diabetes, hypertriglyceridemia and hyperuricemia (P < 0.05), impaired renal health with higher uric acid levels (P < 0.001), and slightly elevated creatinine levels (P = 0.156) with lower estimated glomerular filtration rates (eGFRs) (P = 0.195). The serum autotaxin level was markedly greater in the hypertensive group (239.0±59.6 ng/ml vs. 192.7 ± 49.0 ng/ml; P < 0.01) and was positively associated with systolic blood pressure; diastolic blood pressure; and alanine transaminase, triglycerides (TG), creatinine, and uric acid levels and inversely associated with the eGFR (P < 0.05) among postmenopausal women. Serum autotaxin levels positively predicted hypertension, with an AU-ROC of 0.750 [95% confidence interval (CI): 0.613–0.888] and a Youden index of 0.480 at a cutoff of 225 ng/ml. In the multivariate logistic regression analysis, after adjustment for demographic and metabolic parameters (including age, BMI, ALT, TB, uric acid, FBG, TG, LDL and creatinine), autotaxin (ATX) remained independently positively correlated with the risk of hypertension [odds ratio: 1.016, 95% CI 1.001–1.031; P < 0.05). Conclusions: Among postmenopausal women, the serum autotaxin level is significantly elevated in the hypertensive group compared with age-matched normotensive controls. ATX is related to multiple metabolic disorders and renal health, suggesting that autotaxin has potential as a multiorgan therapeutic target for cardiovascular-metabolic-renal disorders.

The Impact of SARS-CoV-2 on Liver Diseases and Potential Phytochemical Treatments

Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has brought about numerous challenges. One of these challenges is the impact of SARS-CoV-2 on the liver. Although this virus primarily affects the lungs, it can induce elevated transaminase levels and the development of scar tissue in the liver, exacerbating preexisting liver conditions. Individuals with preexisting conditions, such as non-alcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and hepatocellular carcinoma (HCC), face an increased risk of mortality from COVID-19. However, drugs currently used to treat COVID-19 have undesirable side effects that make them unsuitable for patients with pre-existing liver conditions. In this review, we explore the potential of phytochemicals, such as apigenin, berberine, curcumin, epigallocatechin-3-gallate, quercetin, resveratrol and silymarin, for treatment of the liver conditions NAFLD, ALD and HCC. We also discuss significant associations between phytochemicals and COVID-19 by depicting their molecular interactions. Based on the discussed overlapping functions, it is important to assess the therapeutic efficacy of phytochemicals that possess hepatoprotective properties as potential alternative COVID-19 treatments.

Liver magnetic resonance imaging, non-alcoholic fatty liver disease and metabolic syndrome risk in pre-pubertal Mexican boys.

Rising global pediatric obesity rates, increase non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) prevalence, with MetS being a NAFLD risk factor. NAFLD can be asymptomatic, with liver function tests insensitive to mild disease, and liver biopsy, risking complications. Thus, we investigated multiparametric MRI (mpMRI) metrics of liver fat (proton density fat fraction, PDFF) and disease activity (fibro-inflammation; iron-corrected T1, cT1), in a Hispanic pre-pubertal pediatric cohort, with increased risk of NAFLD. Pre-pubertal boys (n = 81) of varying Body-Mass Index (BMI) were recruited in Mexico City. Most children (81%) had normal liver transaminase levels, 38% had high BMI, and 14% had ≥ 3 MetS risk factors. Applying mpMRI thresholds, 12%, 7% and 4% of the cohort had NAFLD, NASH and high-risk NASH respectively. Participants with ≥ 3 MetS risk factors had higher cT1 (834ms vs. 737ms, p = 0.004) and PDFF (8.7% vs. 2.2%, p < 0.001) compared to those without risk factors. Those with elevated cT1 tended to have high BMI and high insulin (p = 0.005), HOMA-IR (p = 0.005) and leptin (p < 0.001). The significant association of increased risk of MetS with abnormal mpMRI, particularly cT1, proposes the potential of using mpMRI for routine pediatric NAFLD screening of high-risk (high BMI, high MetS risk score) populations.

The Effect of Dexmedetomidine and Levobupivacaine in an Experimental Ischemia Reperfusion Model.

Although it has been reported that different molecules are effective in preventing ischemia-reperfusion (I/R) injury, the most effective treatment is still unknown. The rats were divided into four groups of eight rats each. Group C: 1 ml intraperitoneal (IP) isotonic + laparotomy + IP 2 ml isotonic +I/R. Group D: 100 μg kg-1/1 ml IP dexmedetomidine + laparotomy + IP 2 ml isotonic +I/R. Group L: 1 ml IP isotonic + laparotomy + IP levobupivacaine (2.5 mg kg-1/2 ml) +I/R. Group DL: 100 μg kg-1/1 ml IP dexmedetomidine + laparotomy + IP levobupivacaine (2.5 mg kg-1/2 ml) +I/R. Brain, heart, lung, and liver tissue samples were collected for histopathological examination. Biochemically, levels of aspartate amino transaminase, alanine amino transaminase, serum glucose, total antioxidant status (TAS), total oxidant status, ischemia modified albumin, and malondialdehyde were measured in blood samples. Group D mean blood TAS levels were found to be statistically significantly higher than those in Group C and Group L (p=0.037, p=0.048 respectively). Group DL oxidative stress index (OSI) value was found to be statistically significantly lower than that of Group C (p=0.010). Both dexmedetomidine and levobupivacaine demonstrated protective effects in I/R injury. When used in combination, the effects of these treatments were further enhanced, reaching statistical significance. As our literature review found no studies on the combined use of dexmedetomidine and levobupivacaine in I/R injury, it is anticipated that supporting these results with clinical studies may significantly contribute to clinical practice.

Analysis of Clinical and Laboratory Profiles of Patients Hospitalized with Hemorrhagic Fever with Renal Syndrome in Southwestern South Korea.

Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses. Data of 34 patients with HFRS hospitalized at Chosun University Hospital, South Korea, between 2010 and 2021 were retrospectively analyzed. Nested reverse transcription polymerase chain reaction (RT-nPCR) targeting the L segment of hantavirus and sequencing were used for diagnosis. Most cases occurred in men and during the months of October through December. Common symptoms were fever, chills, gastrointestinal symptoms, and myalgia. The common laboratory abnormalities were thrombocytopenia, proteinuria, and elevated levels of serum creatinine, aspartate transaminase, alanine transaminase, and lactate dehydrogenase. Approximately 91.2% of patients had the Hantaan virus with a new genotype cluster, whereas 8.8% had the Seoul virus. Seropositivity based on IgM titer >1:32 on admission was noted in 20.6%, and a 4-fold increase in IgG titer of 1:512 was observed in 11.8%. This study demonstrated that RT-nPCR targeting the L segment of hantaviruses is a more reliable diagnostic method compared to serological testing.

Protective Effect and Mechanism of L-Theanine on Acute Alcoholic Liver Injury in Mice.

Acute alcoholic liver injury (AALI), a global health concern, is exacerbated by excessive episodic drinking. L-theanine (LTA), a compound found in tea leaves, mitigates the AALI-induced liver oxidative stress and inflammation. However, its relationship with alcohol metabolism and its liver-protective mechanism remains unexplored. This study investigates the protective mechanisms of LTA against AALI in mice. The results demonstrate that LTA mitigates liver tissue damage and reduces the serum levels of aspartate aminotransferase and alanine aminotransferase, and liver levels of triglycerides, malondialdehyde, reactive oxygen species (ROS), tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, LTA enhances the activity of ethanol-metabolizing enzymes and decreases ethanol and acetaldehyde serum levels. Mechanistically, LTA accelerates alcohol metabolism by upregulating the hepatic expression of ADH6, ALDH1B1, ALDH2, CAT, and ACSS1 mRNA and protein in AALI mice, LTA downregulates the expression of CYP2E1 mRNA and protein and promoting antioxidative activities thus reducing the accumulation of ROS. This attenuated inflammation by inhibiting the phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα) and downregulating the hepatic expression of NF-κB p65, TNF-α, IL-1β, IL-6 mRNA, and protein. LTA is a beneficial dietary supplement that protects against AALI by modulating alcohol metabolism and the TNF-α/NF-κB pathway.

Disparities in steatosis prevalence in the United States by Race or Ethnicity according to the 2023 criteria

IntroductionThe 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature.MethodsWe undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed.ResultsA total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk.ConclusionsMASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated.

Liver function tests in patients receiving high-intensity care after hospital admission for acute heart failure: the STRONG-HF trial

Abstract Background/Introduction Episodes of acute heart failure (AHF) unfavorably affect extra-cardiac organs such as the liver due to altered hemodynamics and neurohormonal activation. In AHF, elevated levels of levels of alanine aminotransferase (ALT) and total bilirubin (tBil) may reflect congestion and impaired liver function, while lower levels of ALT (which is also produced in muscle cells) correlate with malnutrition and sarcopenia. Thus, the clinical importance of these markers in AHF and the post-discharge period is unclear. Purpose To assess circulating concentrations of ALT and tBil in patients with AHF before discharge and during high-intensity care (HIC) vs usual care follow-up in association with clinical outcomes. Methods ALT and tBil concentrations were measured 1-2 days before discharge in patients hospitalized for AHF (baseline), and again after 90 days of either HIC or usual care according to the STRONG-HF protocol. Baseline values and changes in ALT and tBil were analyzed in association with the primary outcome of all-cause death or HF readmission by day 180. Results At baseline, the median (Q1-Q3) concentrations of ALT and tBil were 21 (15-32) U/L and 14 (10-21) umol/L, respectively. Lower levels of both ALT and tBil were associated with female sex, Black race, lower BMI, higher LVEF, lower hemoglobin, lower creatinine and less frequent atrial fibrillation/flutter, while there were no significant associations with age. Patients with lower ALT, but not tBil, were more likely to have edema, elevated JVP and orthopnea, and used higher loop diuretic doses and less beta-blockers, pre-randomization (Figure, panel A). ALT was inversely associated with risk for the primary outcome (HR 0.81 [95%CI 0.65,1.00) per log increment, p=0.05), while there was no association with risk for tBil (HR 1.04 [95%Ci 0.84-1.28], p=0.73) (Figure, panel B). After 90 days, ALT and tBil concentrations were lower than at baseline, with a greater reduction in tBil in the HIC group vs usual care group (mean -1.7 [95%CI -3.0,-0.4] umol/L, p=0.01), while there was no significant between-group differences in ALT changes (mean -0.6 [95%CI -4.7,3.4] U/L, p=0.75) (Figure, panel C). The treatment effect of HIC over usual care on the primary outcome was consistent across the range of baseline ALT (P-interaction=0.30) and tBil (P-interaction=0.80) (Figure, panel D). Conclusion Contrary to our hypothesis of higher liver function tests with hepatic congestion in AHF, lower ALT was associated with more congestion and worse outcomes among patients hospitalized for AHF in STRONG-HF. There was no prognostic value from tBil levels. This suggests that ALT may be a marker of sarcopenia in these patients. Importantly, the beneficial effect of HIC on clinical outcomes is consistent irrespective of ALT and tBil levels at discharge.Figure

The expression of sICAM-1 influenced by Clonorchis sinensis co-infection in CHB patients.

Soluble Intercellular Adhesion Molecule-1 (sICAM-1) has emerged as an inflammatory biomarker of many essential functions. We investigated the level of sICAM-1 influenced by Clonorchis sinensis (C. sinensis) co-infection in chronic hepatitis B (CHB) patients to explore the degree of liver tissue inflammation and liver function damage after co-infection. The study included data from patients with C. sinensis mono-infection (n=27), hepatitis B virus (HBV) mono-infection (n=32), C. sinensis and HBV co-infection (n=24), post-hepatitis B liver cirrhosis (n=18), post-hepatitis B liver cirrhosis co-infected with C. sinensis (n=16), and healthy controls (n=39). The level of sICAM-1 was measured with specific enzyme-linked immunosorbent assay method. Compared to the healthy control group, all the experimental groups had significantly higher serum sICAM-1 levels. The levels of sICAM-1 in co-infected groups were significantly higher compared to the mono-infection groups and were positively correlated with the levels of glutamate aminotransferase (ALT) and aspartate aminotransferase (AST). Our research findings confirmed that co-infection could exacerbate liver tissue inflammation and liver function damage in patients, could raise the sICAM-1 level, and may lead to the chronicity of HBV infection. These results provide clues for pathological mechanism study and formulating treatment plans.

Effects of Dietary Ferroporphyrin Supplementation on Growth Performance, Antioxidant Capacity, Immune Response, and Oxygen-Carrying Capacity in Gibel Carp (Carassius auratus gibelio)

An eight-week experiment was conducted to study the effects of dietary ferroporphyrin (FPR) supplementation on growth performance, antioxidant capacity, immune response, and oxygen-carrying capacity in gibel carp. The results demonstrated that the addition of FPR increased the moisture content of the whole fish body. Supplementation with 0.01% FPR significantly increased the plasma albumin (ALB), total protein (TP), and total cholesterol (TC) contents. The addition of 0.03% and 0.04% FPR significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively, while the glucose (GLU), TC, and total triglyceride (TG) levels showed opposite trends. In terms of antioxidant capacity, the 0.03% and 0.04% dietary FPR supplementation increased malondialdehyde (MDA) levels. The activity of glutathione peroxidase (GPx) exhibited an opposite trend to MDA levels. The supplementation of 0.03% of FPR resulted in a notable reduction in mRNA expression levels of nrf2, keap1, cat, and gpx. Regarding immunity, 0.01% FPR supplementation down-regulated the expression levels of il-1β mRNA, while 0.02% FPR down-regulated il-6 and nf-κb expression levels. Furthermore, 0.02% FPR supplementation significantly up-regulated the il-10 mRNA expression levels. In terms of oxygen-carrying capacity, high levels of FPR (0.03% and 0.04%) were found to influence the epo and vegf mRNA expression. In conclusion, the incorporation of dietary 0.01–0.02% FPR improved the immune system of gibel carp without affecting their antioxidant and oxygen-carrying capacity. However, supplementation with higher levels of FPR (0.03–0.04%) led to decreased antioxidant and oxygen-carrying capacity.

External Validation of the fullPIERS Risk Prediction Model in a U.S. Cohort of Individuals with Preeclampsia.

To externally validate the fullPIERS risk prediction model in a cohort of pregnant individuals with preeclampsia in the United States. This was a retrospective study of individuals with preeclampsia who delivered at 22 weeks or greater from January 1, 2010, to December 31, 2020. The primary outcome was a composite of maternal mortality or other serious complications of preeclampsia occurring within 48 hours of admission. We calculated the probability of the composite outcome using the fullPIERS prediction model based on data available within 12 hours of admission including, gestational age, chest pain or dyspnea, serum creatinine levels, platelet count, aspartate transaminase levels, and oxygen saturation. We assessed the model performance using the area under the curve (AUC) of the receiver operating characteristic curve. The optimal cutoff point was determined using Liu's method. A calibration plot was used to evaluate the model's goodness-of-fit. Among 1,510 individuals with preeclampsia, 82 (5.4%) experienced the composite outcome within 48 hours. The fullPIERS model achieved an AUC of 0.80 (95% confidence interval: 0.75-0.86). The predicted probability for individuals with the composite outcome (median: 18.8%; interquartile range: 2.9-59.1) was significantly higher than those without the outcome (median: 0.9%; interquartile range: 0.4-2.7). The optimal cutoff point of 5.5% yielded a sensitivity of 70.7% (95% CI: 59.6-80.3), a specificity of 85% (95% CI: 82.7-86.5), a positive likelihood ratio of 4.6 (95% CI: 3.8-5.5), and an odds ratio of 13.3 (95% CI: 8.1-21.8). The calibration plot indicated that the model underestimated risk when the predicted probability was below 1% and overestimated risk when the predicted probability exceeded 5%. The fullPIERS model demonstrated good discrimination in this U.S. cohort of individuals with preeclampsia, suggesting it may be a useful tool for healthcare providers to identify individuals at risk for severe complications.

Effects of l-carnitine on frailty status in patients with liver cirrhosis: A randomized-controlled trial.

Frailty is a common complication in patients with liver cirrhosis, which is linked with augmented rates of morbidity and mortality. In this regard, timely nutritional assessment and intervention have gained scientific attention. L-carnitine may be a promising candidate with its potential to enhance energy metabolism, reduce inflammation, and act as an antioxidant. Therefore, we aimed to assess the impact of l-carnitine supplementation on frailty status and liver function in adults with liver cirrhosis. This double-blinded, randomized, controlled clinical trial study enrolled 77 patients with liver cirrhosis. Patients were randomly allocated into two groups: the control group (n = 42) and the l-carnitine group (n = 35). The l-carnitine group received 500 mg of l-carnitine orally three times a day for 8 weeks, while the control group did not receive any intervention. L-carnitine administration resulted in a significant decrease in alanine transaminase levels (p: 0.043) and partial thromboplastin time (p: 0.036). Furthermore, compared to the control group, l-carnitine treatment led to improvements in prothrombin time (p: 0.008) and international normalized ratio (p: 0.024). However, no significant improvement in the Liver Frailty Index, Freid Frailty Index, and Karnofsky Performance Status Scale (p > 0.05) was observed in the carnitine group after the 8-week intervention period. In conclusion, the administration of l-carnitine exhibited hepatoprotective properties and was correlated with lowered alanine transaminaselevels with improvement in coagulation status in liver cirrhosis patients. Nevertheless, our study indicated that the short-term use of l-carnitine might not significantly improve frailty in these patients.

Targeted Delivery to Dying Cells Through P-Selectin–PSGL-1 Axis: A Promising Strategy for Enhanced Drug Efficacy in Liver Injury Models

To minimize off-target adverse effects and improve drug efficacy, various tissue-specific drug delivery systems have been developed. However, even in diseased organs, both normal and stressed, dying cells coexist, and a targeted delivery system specifically for dying cells has yet to be explored to mitigate off-target effects within the same organ. This study aimed to establish such a system. By examining the surfaces of dying cells in vitro, we identified P-selectin glycoprotein ligand-1 (PSGL-1) as a universal marker for dying cells, positioning it as a potential target for selective drug delivery. We demonstrated that liposomes conjugated with the PSGL-1 binding protein P-selectin had significantly greater binding efficiency to dying cells compared to control proteins such as E-selectin, L-selectin, galectin-1, and C-type lectin-like receptor 2. Using thioacetamide (TAA) to induce hepatitis and hepatocyte damage in mice, we assessed the effectiveness of our P-selectin-based delivery system. In vivo, P-selectin-conjugated liposomes effectively delivered fluorescent dye and the apoptosis inhibitor z-DEVD to TAA-damaged livers in wild-type mice, but not in PSGL-1 knockout mice. In TAA-treated wild-type mice, unconjugated liposomes required a 100-fold higher z-DEVD dose compared to P-selectin-conjugated liposomes to achieve a comparable, albeit less effective, therapeutic outcome in lowering plasma alanine transaminase levels and alleviating thrombocytopenia. This emphasizes that P-selectin conjugation enhances drug delivery efficiency by approximately 100-fold in mice. These results suggest that P-selectin-based liposomes could be a promising strategy for targeted drug delivery, enabling both diagnosis and treatment by specifically delivering cell-labeling agents and rescue agents to dying cells via the P-selectin–PSGL-1 axis at the individual cell level.

Twenty-Week Dietary Supplementation with Beeswax Alcohol (BWA; Raydel®) Ameliorates High-Cholesterol-Induced Long-Term Dyslipidemia and Organ Damage in Hyperlipidemic Zebrafish in a Dose-Dependent Manner: A Comparative Analysis Between BWA and Coenzyme Q10

Background/Objectives: Beeswax alcohol (BWA; Raydel®) is a blend of six long-chain aliphatic alcohols extracted from honeybee wax and is well known for its diverse functionality and health benefits. Herein, the efficacy of a BWA dietary intervention for 20 weeks was assessed to ameliorate high-cholesterol diet (HCD)-induced dyslipidemia and adverse effects on the vital organs of adult zebrafish. Methods: Adult zebrafish were fed different high-cholesterol diets (HCDs; final concentration of 4%, w/w) supplemented with BWA (final concentrations of 0.1%, 0.5% and 1.0%, w/w) or CoQ10 (final concentration of 1.0%). Following 20 weeks of supplementation, blood and different organs (liver, kidney, testes and ovaries) were collected, and biochemical, histological and immunohistochemical analyses were performed. Results: The results demonstrate a dose-dependent effect of BWA of mitigating HCD-induced mortality in zebrafish over the 20-week supplementation period, which was noticeably better than the effect exerted by coenzyme Q10 (CoQ10). Consistently, a dose-dependent effect of BWA consumption of curtailing HCD-induced total cholesterol (TC) and triglyceride (TG) levels and increasing high-density-lipoprotein cholesterol (HDL-C) levels was noticed. Compared with CoQ10 (final concentration of 1.0%, w/w), BWA (final concentration of 1.0%, w/w) displayed a significantly better effect of mitigating HCD-induced dyslipidemia, as evidenced by 1.2-fold (p &lt; 0.05) and 2.0-fold (p &lt; 0.05) lower TC and TG levels and 2.4-fold (p &lt; 0.01) higher HDL-C levels. The histological analysis revealed substantial prevention of fatty liver changes, reactive oxygen species (ROS) generation, cellular senescence and interleukin (IL)-6 production in the hepatic tissue of BWA zebrafish, which was significantly better than the effect exerted by CoQ10. Consistently, compared with CoQ10, significant 25% (p &lt; 0.05) and 35% (p &lt; 0.01) reductions in the HCD-induced elevated levels of the hepatic function biomarkers aspartate aminotransferase and alanine aminotransferase was observed in the BWA group. Likewise, BWA consumption efficiently ameliorated HCD-induced kidney, ovary and testis damage by inhibiting ROS generation, cellular senescence and lipid accumulation. Conclusion: Supplementation with BWA demonstrated higher therapeutic potential than that with CoQ10 to prevent dyslipidemia and organ damage associated with long-term consumption of HCDs.

5-Fluorouracil combined with CalliSphere drug-eluting beads or conventional transarterial chemoembolization for unresectable hepatocellular carcinoma: a propensity score weighting analysis

This study aimed to assess the effectiveness and safety of 5-Fluorouracil (5-Fu) combined with conventional transarterial chemoembolization (cTACE) compared to 5-Fu combined with drug-eluting bead transarterial chemoembolization (DEB-TACE) using CalliSpheres for the treatment of unresectable hepatocellular carcinoma (HCC) using propensity score weighting methods. This retrospective analysis included 131 patients with HCC treated with 5-Fu combined with cTACE (5-Fu-cTACE group, n = 65) or DEB-TACE (5-Fu-DEB-TACE group, n = 66) at the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2022. Based on the baseline data and laboratory indicators, propensity score weighting was used to reduce confounding bias. Modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate clinical efficacy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the disease control rate (DCR), objective response rate (ORR) and adverse events (AEs). PFS was assessed using Kaplan‒Meier analysis and Cox proportional hazards models. The ORRs at 1 month (M1) after treatment in the 5-Fu-DEB-TACE group and 5-Fu-cTACE group were 90.9% and 76.9%, respectively (P = 0.029), while at this time, the DCRs were 93.9% in the 5-Fu-DEB-TACE group and 90.8% in the 5-Fu-cTACE group (P = 0.494). At 3 months (M3) after treatment, the 5-Fu-DEB-TACE group had a higher ORR (84.8% vs. 56.9%, P < 0.001) and DCR (84.8% vs. 72.3%, P = 0.08). The ORR at 6 months (M6) was also higher in the 5-Fu-DEB-TACE group than in the 5-Fu-cTACE group (72.7% vs. 50.8%, P = 0.01). The median PFS after treatment with 5-Fu-DEB-TACE was longer than that after treatment with 5-Fu-cTACE (11 months vs. 6 months) (P = 0.004). Cox proportional hazards regression analysis indicated that 5-Fu-DEB-TACE (HR = 0.590, P = 0.044), Model for End-Stage Liver Disease (MELD) intermediate risk (HR = 2.470, P = 0.010), BCLC stage B (HR = 2.303, P = 0.036), BCLC stage C (HR = 3.354, P = 0.002) and ascitic fluid (HR = 2.004, P = 0.046) were independent predictors of PFS. No treatment-related deaths occurred in this study. The 5-Fu-DEB-TACE group had a greater incidence of abdominal pain (72.7% vs. 47.7%, P = 0.003). However, the incidence of postoperative elevated transaminase levels was higher in the 5-Fu-cTACE group (83.1% vs. 66.6%, P = 0.031). Subgroups analysis showed patients receiving 5-Fu-DEB-TACE have better PFS compared to those receiving 5-Fu-cTACE in the BCLC stage A group (P = 0.0093), BCLC stage B group (P = 0.0096), multifocal group (P = 0.0056), Child-Pugh stage A group (P<0.001), non- extrahepatic metastasis group (P = 0.022), non-vascular invasion group (P = 0.0093), and the group with a largest tumor diameter ≥ 5 cm (P = 0.0048). At M1, M3, and M6, patients with preserved liver function and in some cases of low tumor burden had higher Objective Response Rate (ORR) and Disease Control Rate (DCR) (P < 0.05). Compared with 5-Fu-cTACE, 5-Fu-DEB-TACE has superior therapeutic efficacy, prolongs PFS, and reduces hepatotoxicity. However, it is associated with an increased incidence of postoperative abdominal pain.

Growth performances of Clarias gariepinus juveniles fed with Jatropha curcas seed meal

Jatropha curcas is an oil producing seed with high nutritional qualities for consumption. However, due to inherent anti-nutritional factors, appropriate processing is necessary to improve its nutrients utilization. This study was aimed at processing J. curcas using solvent-extraction method and evaluating its inclusion effects in the diet for Clarias gariepinus on its growth status. J. curcas meal was extracted using 80 % methanol to remove phorbol esters and other anti-nutrients. Thereafter, five iso-nitrogenous diets (40 % crude protein) were formulated containing J. curcas meal replacements of soybeans meal at 0 % (TRT0), 25 % (TRT25), 50 % (TRT50), 75 % (TRT75) and 100 % (TRT100) and fed to C. gariepinus for 70 days. Results showed that TRT25 fish had the highest mean weight gain and specific growth. The serum alkaline phosphate, alanine aminotransferase, and aspartate aminotransferase levels began to rise significantly (p ≤ 0.05) at 50 % replacement. Likewise, the assessment of gut ecology and morphology indicated that TRT25 had significantly (p ≤ 0.05) the highest gut bacteria colony forming unit (2.60 ×104±0.02cfu/g) and most favorable area of absorption (0.16±0.01 cm2). The histopathological observation of the fish intestine, liver and gills indicated no visible deformity in TRT0 and TRT25 fish. However, various degrees of degenerations were observed in the fish fed with 50 % and higher inclusion of J. curcas. This study showed that methanol-extracted J. curcas meal can be effectively utilized for C. gariepinus at 25 % of replacement.

CHARACTERISTICS AND OUTCOME OF LEFT MAIN STEM PCI AMONG WOMEN

Left main stem disease is a severe condition affecting a major coronary artery, traditionally treated with coronary artery bypass grafting. Recent advancements in percutaneous coronary intervention have made it a viable option, particularly for women who face unique risks and outcomes compared to men. Objective: This study aims to evaluate the characteristics and outcomes of percutaneous coronary intervention for left main stem disease in female patients, focusing on procedural outcomes and changes in laboratory parameters before and after the intervention. Methods: A prospective observational study was conducted from January to July 2024 with 68 female patients, aged 18 and above, from Fauji Foundation Hospital Rawalpindi. Various percutaneous coronary intervention techniques were used, and data on ejection fractions, access methods, and procedural specifics were collected. Pre- and post-procedural laboratory outcomes including haemoglobin, creatinine, platelet counts, and alanine aminotransferase levels were analyzed. Results: The mean age of participants was 63.6 years. Diabetes, hypertension, and dyslipidemia were common comorbidities. Laboratory results showed stable haemoglobin levels, slight increases in creatinine, and consistent platelet counts and ALT levels post-procedure. Statistical analysis revealed no significant changes in these parameters, indicating minimal impact on anaemia, renal function, and platelet or liver function. Conclusion: percutaneous coronary intervention for the left main stem in females generally results in stable laboratory outcomes with minimal impact on anaemia, renal function, and platelet or liver function. The procedure is safe with a low mortality rate. Continuous monitoring is recommended to manage any potential complications effectively.

Machine Perfusion or Straight to Transplant? Predictive Value of Flavin Mononucleotide Levels in Flush Solution of Human Liver Allograft.

This study examined the predictive value of Flavin Mononucleotide (FMN) levels in the flush solution used during cold storage of donor livers on outcomes post-transplantation. Static cold storage for liver grafts induces hypoxia with subsequent impaired mitochondrial function and Flavin Mononucleotide (FMN) release upon reperfusion. This study enrolled 62 recipients who received whole liver grafts from donation after brain death (n=50) and circulatory death donors (n=12) between June 2022 and July 2023. FMN concentrations were measured in flush solutions on the back-table. ROC-curve analysis identified an FMN level cut-off for graft survival. Post-transplant outcomes were examined according to FMN levels. FMN level was significantly associated with graft survival, with an area-under-the-curve (AUC) of 0.858 (95%CI: 0.754-0.963, P<0.001), outperforming the donor risk index (AUC 0.571, 95%CI: 0.227-0.915, P=0.686). The study cohort was divided into low-FMN (<37.5ng/mL, n=40) and high-FMN groups (≥37.5ng/mL, n=22). The low-FMN group had superior one-year graft survival compared with the high-FMN group (100% vs. 77%, P=0.003). Levels of transaminases within 7 days post-transplant were significantly higher in the high-FMN group (P=0.003). The high-FMN group developed acute rejections (41% vs. 15%, P=0.023) and early allograft dysfunction (50% vs. 20%, P=0.014) more frequently. Median comprehensive complication index in the high-FMN group was significantly higher (54 [interquartile range, 40-78] vs. 42 [interquartile range, 28-52], P=0.017). The FMN level measured in donor livers' cold storage flush solution is a valid biomarker to predict post-transplant outcomes. Liver grafts with high FMN levels may benefit from machine perfusion to improve outcomes.

Анализ эффективности и безопасности применения CFTR-модулятора лумакафтор/ивакафтор у пациентов с муковисцидозом в разных возрастных группах

Russia’s first registered CFTR-modulator lumacaftor/ivacaftor was developed for patients with cystic fibrosis (CF) with the F508del/F508del genotype. The purpose of this research was to study the efficacy and safety of lumacaftor/ivacaftor therapy in different age groups. Materials and methods used: the data of homozygotes for F508del aged 2 to 18 y/o in the Russian CF Patient Registry who had been treated with lumacaftor/ivacaftor were analyzed. The effectiveness of therapy was evaluated in 3 age groups based on examination data, nutritional status, spirometry, sweat test at the start of therapy and after 12 months. In order to assess the safety, examination data, assessment of adverse events (AE), blood biochemical parameters, blood pressure and lens condition were taken into account in 334 pediatric patients in the first month of therapy and in 180 after 12 months. Results: decrease in sweat conductivity was noted in three age groups (p&lt;0.001), only in the 2 to 6 y/o age group were negative values obtained in 6.8%. An increase in BMI was observed in the 6 to 12 y/o and 12 to 18 y/o age groups (р&lt;0.001) whilst an improvement in FVC was observed only in the 12 to 18 y/o age group (p=0.015). Changes in biochemical parameters were statistically significant, both downward and upward, only in the age groups of 6 to 12 y/o and 12 to 18 y/o, changing not significantly. Withdrawal of the drug was required in only a single patient with a persistent increase in transaminase level. Fluctuations in blood pressure occurred within the normal age limits. Frequency of AE was comparable with the results of other studies, it was noted at the start in all groups and after 12 months more often in the age group of 12 to 18 y/o. The best tolerance was noted in the age group of 2 to 6 y/o. Conclusion: for the first time, the efficacy and tolerability of lumacaftor/ivacaftor in patients with CF in Russia was studied against the age aspect according to the 2022-2024 Registry. In the 2 to 6 y/o age group, the achievement of normal sweat test values and the lowest number of adverse reactions were noted, while in the 12 to 18 y/o age group, the positive dynamics were noted for a greater number of indicators, incl. an increase in FVC.

Diagnostic role of the fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score as a noninvasive tool for liver fibrosis scoring.

Nonalcoholic fatty liver disease (NAFLD) is characterized by liver fibrosis, which serves as a crucial indicator of its progression and prognosis. Owing to the limitations of biopsy, which is the gold standard for measuring liver fibrosis, a reliable and noninvasive marker is required. We evaluated the diagnostic role of the fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) in patients with NAFLD with varying severities of liver fibrosis. The FIB-4 index and NFS were calculated using laboratory data from 121 patients who underwent liver biopsies between January 2022 and December 2023. The results were compared with those of the Scheuer scoring system for liver biopsies (F0, F1 + F2, and F3 + F4) to determine the sensitivity and specificity of the FIB-4 index and the liver disease fibrosis score in detecting and staging liver fibrosis. Twenty-one patients had advanced fibrosis (F3-F4), and 100 had minimal or mild fibrosis (F0-F2). The degree of liver fibrosis increased with decreased albumin, alanine aminotransferase and platelet count levels, and increasing age. Receiver operating characteristic curve analysis for the FIB-4 index and NFS revealed that the areas under the curve for the FIB-4 index and NFS were 0.895 (95% confidence interval: 0.836-0.954) and 0.882 (95% confidence interval: 0.813-0.952), respectively. The FIB-4 indices showed 95.24% sensitivity at a cutoff point of 1.30, and 85% specificity at a cutoff point of 2.67, while the NFS indices showed 95.24% sensitivity at -1.455 cutoff point and 95% specificity at a cutoff point of 0.676. The FIB-4 index and NFS may replace biopsy for the detection of fibrosis in patients with NAFLD.