Normal Liver Research Articles

Increase in cathepsin K gene expression in Duchenne muscular dystrophy skeletal muscle.

Dystrophinopathy is caused by alterations in the dystrophin gene. The severe phenotype, Duchenne muscular dystrophy (DMD), is caused by a lack of dystrophin in skeletal muscles, resulting in necrosis and regenerating fibers, inflammatory cells, and muscle fibrosis. Progressive muscle weakness is a characteristic finding of this condition. Here, we encountered a rare case of a 10-year-old patient with asymptomatic dystrophinopathy with no dystrophin expression and investigated the reason for the absence of muscle weakness to obtain therapeutic insights for DMD. Using RNA-seq analysis, gene expression in skeletal muscles was compared among patients with asymptomatic dystrophinopathy, three patients with typical DMD, and two patients without dystrophinopathy who were leading normal daily lives. Cathepsin K (CTSK), myosin heavy chain 3 (MYH3), and nodal modulator 3-like genes exhibited a >8-fold change, whereas crystallin mu gene (CRYM) showed a <1/8-fold change in patients with typical DMD compared with their expression in the patient with asymptomatic dystrophinopathy. Additionally, CTSK and MYH3 expression exhibited a >16-fold change (P < 0.01), whereas CRYM expression showed a <1/16-fold change (P < 0.01) in patients with typical DMD compared with their expression in those without dystrophinopathy. CTSK plays an essential role in skeletal muscle loss, fibrosis, and inflammation in response to muscles injected with cardiotoxin, one of the most common reagents that induce muscle injury. Increased CTSK expression is associated with muscle injury or necrosis in patients with DMD. The lack of muscle weakness in the patient with asymptomatic dystrophinopathy might be attributed to the low CTSK expression in the muscles. To the best of our knowledge, this is the first report to demonstrate that CTSK expression was significantly higher in the skeletal muscles of patients with DMD with a typical phenotype than in those without dystrophinopathy.

Suspected olfactory meningioma and synchronous pituitary microadenoma in a canine patient treated with radiation therapy

The authors report on the rare occurrence of dual synchronous primary brain tumors in a canine patient, successful treatment with radiation therapy, and medical therapy with patient stabilization for almost three years. A 12.5-year-old spayed mixed-breed female Labrador was referred to Purdue Veterinary Hospital to treat hyperadrenocorticism of suspected pituitary origin. During MRI imaging, the presence of two possible brain neoplasms was detected: a possible right olfactory bulb meningioma and a microadenoma of the pituitary gland. The patient was treated with a fractionated course of radiation in both tumors, 15 treatments of 3Gy, which limited the tumor growth. Mitotane therapy corrected the hormonal dysregulation. The dog had a normal life for nearly three years and recently passed. Cancer cells were not found at necropsy. No MEN1 germline mutations were identified in constitutional DNA (from blood) via high-coverage whole genome sequencing.

A Decalogue on Enhanced Recovery After Breast Augmentation Surgery (ERABAS).

Medical and technical advances have changed the state of postoperative surgical patient care, allowing for better and faster recovery. Since its publication, predictable 24-hour recovery in breast augmentation surgery has been controversial and has generated discussion. In this study, we present a novel, easy, and reproducible protocol for Enhanced Recovery After Breast Augmentation Surgery (ERABAS), along with a summary of the ten points to follow. We conducted a retrospective study of all primary breast augmentation surgeries performed between 2010 and 2020 by a private activity. All surgeries were performed by the same surgeon according to the same protocol, and all implants were obtained from the same company. Data were evaluated using two binary logistic regression models, taking as variables responses to recovery time and postoperative pain and as predictor or explanatory variables to the factors age, smoking, size, and location of the implant. In total, 2906 patients were included in this study. Of these, 2770 patients (95%) immediately returned to normal life within the first 24h, 129 achievednormal life in four days, and only seven needed a week to recover. In these seven patients, the main acute complications were hemorrhage and acute hematoma. The implants were always round; textured implants were used in 88.8% of patients, while smooth implants were used in 11.2%. A subfascial pocket was used in 934 patients, and a dual-plane pocket was performed for 1972 patients. The only factor that showed a significant effect on recovery time was the location of the implant (p < 0.05), with the dual-plane pocket being the intervention associated with a later recovery, specifically a probability of recovery after 24 hour, 2.86 times greater than subfascial. The ERABAS protocol allowed rapid return to daily activities with low complication rates. Further prospective comparative multicenter studies are required to confirm these results. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Quantitative and qualitative evaluation of high-quality hepatobiliary phase imaging with shortened timing and utility in patients with compromised liver function.

To compare high flip angle (FA) hepatobiliary-phase (hHBP) imaging with variable time intervals to conventional HBP (cHBP) to assess the impact of increased FA on image quality in shortened HBP imaging. Data from 218 patients, divided into normal liver group (n = 184) and decompensated liver group (n = 34), who underwent liver magnetic resonance imaging (MRI) including 10-min, 15-min, 20-min hHBP, and cHBP were analyzed. Signal-to-noise ratio (SNR), contrast-ratio (CR), contrast-to-noise ratio (CNR), signal intensity ratios (SIRs), and relative enhancement (RE) of the liver were calculated for quantitative analysis. Sharpness, noise, and artifacts of the image, contrast media visibility, overall image quality, and lesion conspicuity were evaluated by two abdominal radiologists. Quantitative analysis showed that SNR, RE, SIR for liver/muscle, liver/spleen, and CR of all hHBP images demonstrated a significantly higher value compared to cHBP images in the normal liver group (p < 0.001). These values were also superior in the normal liver group compared to the decompensated liver group (p < 0.01). In qualitative analysis, both normal and decompensated liver groups exhibited significantly superior image sharpness in all hHBP images compared to cHBP images and the overall image quality of the 15-min and 20-min hHBP did not show significant difference compared to cHBP. All values tended to be better in the normal liver group than the decompensated liver group with statistical significance except for lesion conspicuity (p < 0.01). High-FA HBP has proven to be a valuable image acquisition method, potentially shortening liver MR imaging time while maintaining acceptable image quality.

ALT in Preeclampsia

Background: Preeclampsia is the most frequent cause of abnormal liver function test in pregnancy. Women with preeclampsia and raised serum alanine aminotransferase (ALT) have chance of greater proteinuria and more maternal complications than those with normal liver function. Objective: The present study was designed to assess the association of serum ALT with preeclampsia. Materials and method: A case control study was conducted in the Department of Biochemistry, Dhaka Medical College,Dhaka, Bangladesh, from July 2010 to June 2011. From the pregnant women in third trimester of pregnancy attending in Obstetrics and Gynecology Department of Dhaka Medical College Hospital, 50 diagnosed cases of preeclampsia were selected purposively as cases and 50 normal healthy pregnant women as controls. Serum ALT concentration was measured in all the study subjects. Results: The mean serum ALT concentration in cases and controls were 57.92±20.99 U/L and 15.46±2.66 U/L respectively. The level was significantly higher in cases than that of controls (p=0.001). Conclusion: The study revealed that increased serum ALT concentration is associated with preeclampsia. Delta Med Col J. Jan 2021;9(2): 65-68

Pharmacy students' process of learning of real patients in a simple first-person perspective patient simulation exercise — A qualitative analysis

IntroductionPharmacists need more insight into patients' perspectives on medicine to target their counseling and improve patient outcomes. Patient simulation exercises, where pharmacy students are asked to consume medicine-like products, have been shown to foster such understandings, although the specifics of how this occurs, in particularly, how students turn their first-person perspectives toward generalizations about real patients' lives with medicines, are not well documented.The aim was to identify central aspects of the learning process by introducing reflection questions about real patients and follow students' development during a study period. MethodsThe study was conducted with students in their 4th semester in the second year of Pharmacy Education at the University of Copenhagen who were asked to respond to free text questions in a survey instrument about their daily experiences of taking a licorice product for one week as well as answering patient reflection questions. Qualitative deductive analysis was performed by coding students' experiences according to concepts of ‘experiential learning’. Pattern identification within each concept was then inferred, as were their interrelationships. ResultsPatient reflection questions enabled students to turn their first-person perspectives toward relevant generalizations about real patients' lives with medicines, including involved psychological mechanisms and how real patient groups differ in their ability to take medicine regularly. Students who during the week faced challenges with following the required dosing scheme came to more nuanced realizations that medicine adherence requires special efforts and restricts one's daily life; hence, negative emotions were involved in the learning process. ConclusionsThe design of the simple patient simulation exercise gave rise to new types of insights into real patients' lives with medicines. Negative emotions due to interference between the requirements of the exercise and students' normal social lives, as well as commitment to the exercise, were important aspects of this process.

In vivoHyperpolarized Metabolic Imaging to Monitor the Progression of Hepatitis B Virus (HBV)-Related Hepatitis to Liver Fibrosis.

This study aimed to assess metabolic changes to monitor the progression from normal liver to hepatitis B virus (HBV)-related hepatitis and liver fibrosis using hyperpolarized 13C magnetic resonance imaging (MRI). Hepatitis was induced in mice (n = 16) via hydrodynamic injection of HBV 1.2 plasmid (25μg). Among them, liver fibrosis was induced in the mice (n = 8) through weight-adapted administration of thioacetamide with ethanol. Normal control mice (n = 8) were injected with a phosphate buffer solution. Subsequently, a hyperpolarized 13C MRI was performed on the mouse liver in vivo. The level of hepatitis B surface antigen (HBsAg) in blood serum was measured. Statistical analysis involved comparing the differential metabolite ratios, blood biochemistry values, and body weight among the three groups using the Kruskal-Wallis one-way analysis of variance. HBsAg was absent in the normal and fibrosis groups, while it was detected in the hepatitis group. The ratios of [1-13C] lactate/pyruvate, [1-13C] alanine/pyruvate, [1-13C] lactate/total carbon, and [1-13C] alanine/total carbon were significantly lower in the normal control group than in the hepatitis and fibrosis groups (p < 0.05). Moreover, these ratios were significantly higher in the fibrosis group than in the hepatitis group (p < 0.05). However, no significant differences were observed in either [1-13C] pyruvate-hydrate/pyruvate or [1-13C] pyruvate-hydrate/total carbon among the three groups. The levels of [1-13C] lactate and [1-13C] alanine in vivo may serve as valuable indicators for differentiating between HBV-related hepatitis, liver fibrosis, and normal liver.

Pharmacokinetics and safety of GST-HG171, a novel 3CL protease inhibitor, in Chinese subjects with impaired and normal liver function.

GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C-like (3CL) protease inhibitor that was recently approved for treating mild to moderate coronavirus disease 2019 patients in China. Since cytochrome P450 (CYP) enzymes, primarily CYP3A, are the main metabolic enzymes of GST-HG171, hepatic impairment may affect its pharmacokinetic (PK) profile. Aiming to guide clinical dosing for patients with hepatic impairment, this study, using a non-randomized, open-label, single-dose design, assessed the impact of hepatic impairment on the PK, safety, and tolerability of GST-HG171. Patients with mild and moderate hepatic impairment along with healthy subjects were enrolled (n = 8 each), receiving a single oral dose of 150 mg GST-HG171, with concurrent administration of 100 mg ritonavir to sustain CYP3A inhibition before and after GST-HG171 administration (-12, 0, 12, and 24 hours). Compared to subjects with normal hepatic function, the geometric least-squares mean ratios (90% confidence intervals) for GST-HG171's maximum plasma concentration (Cmax), area under the concentration-time curve up to the last quantifiable time (AUC0-t), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) in subjects with mild hepatic impairment were 1.14 (0.99, 1.31), 1.07 (0.88, 1.30), and 1.07 (0.88, 1.29), respectively. For moderate hepatic impairment, the ratios were 0.87 (0.70, 1.07), 0.82 (0.61, 1.10), and 0.82 (0.61, 1.10), respectively. Hepatic impairment did not significantly alter GST-HG171's peak time (Tmax) and elimination half-life (T1/2). GST-HG171 exhibited good safety and tolerability in the study. Taken together, mild to moderate hepatic impairment minimally impacted GST-HG171 exposure, suggesting no need to adjust GST-HG171 dosage for patients with mild to moderate hepatic impairment in the clinic.Clinical TrialsRegistered at ClinicalTrials.gov (NCT06106113).

Circ_0000069 promotes the development of hepatocellular carcinoma by regulating CCL25

BackgroundHepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, influenced by aberrant circRNA expression. Investigating circRNA-miRNA-mRNA interactions can unveil underlying mechanisms of HCC and identify potential therapeutic targets.MethodsIn this study, we conducted differential analyses of mRNAs, miRNAs, and circRNAs, and established their relationships using various databases such as miRanda, miRDB, and miTarBase. Additionally, functional enrichment and immune infiltration analyses were performed to evaluate the roles of key genes. We also conducted qPCR assays and western blotting (WB) to examine the expression levels of circRNA, CCL25, and MAP2K1 in both HCC cells and clinical samples. Furthermore, we utilized overexpression and knockdown techniques for circ_0000069 and conducted wound healing, transwell invasion assays, and a tumorigenesis experiment to assess the migratory and invasive abilities of HCC cells.ResultsOur findings revealed significant differential expression of 612 upregulated genes and 1173 downregulated genes in HCC samples compared to normal liver tissue. Additionally, 429 upregulated circRNAs and 453 downregulated circRNAs were identified. Significantly, circ_0000069 exhibited upregulation in HCC tissues and cell lines. The overexpression of circ_0000069 notably increased the invasion and migration capacity of Huh7 cells, whereas the downregulation of circ_0000069 reduced this capability in HepG2 cells. Furthermore, this effect was counteracted by CCL25 silencing or overexpression, separately. Animal studies further confirmed that the overexpression of hsa_circ_0000069 facilitated tumor growth in xenografted nude mice, while the inhibition of CCL25 attenuated this effect.ConclusionCirc_0000069 appears to promote HCC progression by regulating CCL25, suggesting that both circ_0000069 and CCL25 can serve as potential therapeutic targets.

Reprogramming of Glutamine Amino Acid Transporters Expression and Prognostic Significance in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy and is a major cause of cancer-related mortality in the world. This study aimed to characterize glutamine amino acid transporter expression profiles in HCC compared to those of normal liver cells. In vitro and in vivo models of HCC were studied using qPCR, whereas the prognostic significance of glutamine transporter expression levels within patient tumors was analyzed through RNAseq. Solute carrier (SLC) 1A5 and SLC38A2 were targeted through siRNA or gamma-p-nitroanilide (GPNA). HCC cells depended on exogenous glutamine for optimal survival and growth. Murine HCC cells showed superior glutamine uptake rate than normal hepatocytes (p &lt; 0.0001). HCC manifested a global reprogramming of glutamine transporters compared to normal liver: SLC38A3 levels decreased, whereas SLC38A1, SLC7A6, and SLC1A5 levels increased. Also, decreased SLC6A14 and SLC38A3 levels or increased SLC38A1, SLC7A6, and SLC1A5 levels predicted worse survival outcomes (all p &lt; 0.05). Knockdown of SLC1A5 and/or SLC38A2 expression in human Huh7 and Hep3B HCC cells, as well as GPNA-mediated inhibition, significantly decreased the uptake of glutamine; combined SLC1A5 and SLC38A2 targeting had the most considerable impact (all p &lt; 0.05). This study revealed glutamine transporter reprogramming as a novel hallmark of HCC and that such expression profiles are clinically significant.

Prospective longitudinal cohort study of quantitative muscle magnetic resonance imaging in a healthy control population.

Quantitative muscle magnetic resonance imaging (qMRI) is a valuable methodology for assessing muscular injuries and neuromuscular disorders. Notably, muscle diffusion tensor imaging (DTI) gives insights into muscle microstructural and macrostructural characteristics. However, the long-term reproducibility and robustness of these measurements remain relatively unexplored. The purpose of this prospective longitudinal cohort study was to assess the long-term robustness and range of variation of qMRI parameters, especially DTI metrics, in the lower extremity muscles of healthy controls under real-life conditions. Twelve volunteers (seven females, age 44.1 ± 12.1 years, body mass index 23.3 ± 2.0 kg/m2) underwent five leg muscle MRI sessions every 20 ± 4 weeks over a total period of 1.5 years. A multiecho gradient-echo Dixon-based sequence, a multiecho spin-echo T2-mapping sequence, and a spin-echo echo planar imaging diffusion-weighted sequence were acquired bilaterally with a Philips 3-T Achieva MR System using a 16-channel torso coil. Fifteen leg muscles were segmented in both lower extremities. qMRI parameters, including fat fraction (FF), water T2 relaxation time, and the diffusion metrics fractional anisotropy (FA) and mean diffusivity (MD), were evaluated. Coefficients of variance (wsCV) and intraclass correlation coefficients (ICCs) were calculated to assess the reproducibility of qMRI parameters. The standard error of measurement (SEM) and the minimal detectable change (MDC) were calculated to determine the range of variation. All tests were applied to all muscles and, subsequently, to each muscle separately. wsCV showed good reproducibility (≤ 10%) for all qMRI parameters in all muscles. The ICCs revealed excellent agreement between time points (FF = 0.980, water T2 = 0.941, FA = 0.952, MD = 0.948). Random measurement errors assessed by SEM and the MDC were low (< 12%). In conclusion, in this study, we showed that qMRI parameters in healthy volunteers living normal lives are stable over 18 months, thereby defining a benchmark for the expected range of variation over time.

Ankrd1 inhibits the FAK/Rho-GTPase/F-actin pathway by downregulating ITGA6 transcriptional to regulate myoblast functions.

Skeletal muscle constitutes the largest percentage of tissue in the animal body and plays a pivotal role in the development of normal life activities in the organism. However, the regulation mechanism of skeletal muscle growth and development remains largely unclear. This study investigated the effects of Ankrd1 on the proliferation and differentiation of C2C12 myoblasts. Here, we identified Ankrd1 as a potential regulator of muscle cell development, and found that Ankrd1 knockdown resulted in the proliferation ability decrease but the differentiation level increase of C2C12 cells. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyzes as well as RNA-seq results showed that Ankrd1 knockdown activated focal adhesion kinase (FAK)/F-actin signal pathway with most genes significantly enriched in this pathway upregulated. The integrin subunit Itga6 promoter activity is increased when Ankrd1 knockdown, as demonstrated by a dual-luciferase reporter assay. This study revealed the molecular mechanism by which Ankrd1 knockdown enhanced FAK phosphorylation activity through the alteration of integrin subunit levels, thus activating FAK/Rho-GTPase/F-actin signal pathway, eventually promoting myoblast differentiation. Our data suggested that Ankrd1 might serve as a potential regulator of muscle cell development. Our findings provide new insights into skeletal muscle growth and development and valuable references for further study of human muscle-related diseases.

A novel iheyamine A derivative L42 suppresses acute myeloid leukemia via dual regulation of the PI3K/AKT/FOXO3a axis and TNF signaling pathway

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies and the development of new drugs is crucial for the treatment of this lethal disease. Iheyamine A is a nonmonoterpenoid azepinoindole alkaloid from the ascidian Polycitorella sp., and its anticancer mechanism has not been investigated in leukemias. Herein, we showed the significant antileukemic activity of L42 in AML cell lines HEL, HL-60 and THP-1. The IC50 values were 0.466±0.099 µM, 0.356±0.023 µM, 0.475±0.084 µM in the HEL, HL-60 and THP-1 cell lines, respectively, which were lower than the IC50 (2.594±0.271 µM) in the normal liver cell line HL-7702. Furthermore, L42 significantly inhibited the growth of peripheral blood mononuclear cells (PBMCs) from an AML patient. In vivo, L42 effectively suppressed leukemia progression in a mouse model induced by Friend murine leukemia virus (F-MuLV). Mechanistically, we showed that L42 induced cell cycle arrest and apoptosis in leukemia cell lines. RNA sequencing analysis of L42-treated THP-1 cells revealed that the differentially expressed genes (DEGs) were enriched in the cell cycle and apoptosis and predominantly enriched in the PI3K/AKT pathway. Accordingly, L42 decreased the expression of the phospho-PI3K (p85), phospho-AKT and phospho-FOXO3a. Docking and CETSA analysis indicated that L42 bound to the PI3K isoform p110α (PIK3CA), which was implicated in the suppression of the PI3K/AKT pathway. L42 was also shown to initiate the TNF signaling-mediated apoptosis. Moreover, L42 exhibited stronger anti-leukemia activity and sensitivity in IDH2-mutant HEL cells than in IDH2-wild-type control. In conclusion, L42 effectively suppresses cell proliferation and triggers apoptosis in AML cell lines in part through inhibition of the PI3K/AKT signaling pathway to restore FOXO3a expression and activation of the TNF signaling pathway. Thus, the iheyamine A derivative L42 represents a novel candidate for AML therapy.

Effects of dissolved organic matter on distribution characteristics of heavy metals and their interactions with microorganisms in soil under long-term exogenous effects

Long-term waste accumulation (LTWA) in soil not only alters its physical and chemical properties but also affects heavy metals and microorganisms in polluted soil through the dissolved organic matter (DOM) it produces. However, research on the impact of DOM from LTWA on heavy metals and microorganisms in polluted soil is limited, which has resulted in an incomplete understanding of the mechanisms involved in LTWA soils remediation. This study focuses on the DOM generated by waste accumulation and analyses the physicochemical properties, microbial community structure, and vertical distribution of heavy metals in four types of LTWA soils at different depths (0–100 cm). A causal analysis is conducted using structural equation modelling. The results indicate that due to the retention effect of the soil and microorganisms, heavy metal pollution is concentrated on the soil surface layer (>30 cm). With increasing depth, there is a decrease in heavy metal concentration and an increase in microbial diversity and abundance. DOM plays a significant role in regulating the concentration of soil heavy metals and the diversity and abundance of microorganisms. The DOM from different soils gradually transforms into substances dominated by tyrosine, tryptophan, and fulvic acid, which sustain the normal life activities and gene expression of microorganisms. Bacteria such as Pseudarthrobacter, Desulfurivibrio, Thiobacillus, and Sulfurimonas, which are involved in energy transformation, along with genes such as water channel protein and YDIF, which enhance heavy metal metabolism, ensure that microbial communities can maintain basic life processes in polluted environments and gradually select for dominant species that are adapted to heavy metal pollution. These novel discoveries illuminate the potential for modulating the composition of DOM to amplify microbial activity, while concurrently offering insights into the migration patterns of various long-term exogenous pollutants. This foundational knowledge provides a foundation for the development of efficacious remediation strategies.

Peridroplet mitochondria are associated with the severity of MASLD and the prevention of MASLD by diethyldithiocarbamate

Mitochondria can contact lipid droplets (LDs) to form peridroplet mitochondria (PDM) which trap fatty acids in LDs by providing ATP for triglyceride synthesis, and prevent lipotoxicity. However, the role of PDM in metabolic dysfunction associated steatotic liver disease (MASLD) is not clear. Here, the features of PDM in dietary MASLD models with different severity in mice were explored. Electron microscope photographs show that LDs and mitochondria rarely come into contact with each other in normal liver. In mice fed with high-fat diet, PDM can be observed in the liver as early as the beginning of steatosis in hepatocytes. For the first time, we show that PDM in mouse liver varies with the severity of MASLD. PDM and cytosolic mitochondria (CM) were isolated from the liver tissue of MASLD and analyzed by quantitative proteomics. Compared with CM, PDM have enhanced mitochondrial respiration and ATP synthesis. Diethyldithiocarbamate (DDC) alleviates choline-deficient, L-amino acid-defined diet-induced MASLD, while increases PDM in the liver. Similarly, DDC promotes the contact of mitochondria-LDs in steatotic C3A cells in vitro. Meanwhile, DDC promotes triglyceride synthesis and improves mitochondrial dysfunction in MASLD. In addition, DDC upregulates perilipin 5 both in vivo and in vitro, which is considered as a key regulator in PDM formation. Knockout of Plin5 inhibits the contact of mitochondria-LDs induced by DDC in C3A cells. These results demonstrate that PDM might be associated with the progression of MASLD and the prevention of MASLD by DDC. The regulation of PDM might be a new pharmacological strategy for MASLD.

Liver injury in paraquat poisoning: A retrospective cohort study.

Liver injury is one of the common complications of paraquat (PQ) poisoning, but whether the degree of liver injury is related to patient prognosis is still controversial. This study aimed to investigate whether liver injury was a risk factor for death in PQ-poisoned patients. We conducted a retrospective cohort study of PQ-poisoned patients from the past 10 years (2011-2020) from a large tertiary academic medical centre in China. PQ-poisoned patients were divided into a normal liver function group (n = 580) and a liver injury group (n = 60). Propensity score matching (PSM) analysis was then performed. A total of 640 patients with PQ poisoning were included in this study. To reduce the impact of bias, dose of PQ, urinary PQ concentration and time from poisoning to hospital admission were matched between the two groups. A 3:1 PSM analysis was performed, ultimately including 240 patients. Compared with the normal liver function group, patients in the liver injury group were older, had a higher R value ([ALT/ULN]/[ALP/ULN]) (p < .001) and had a higher mortality rate. Cox regression analysis showed that there was no significant association between alanine aminotransferase, alkaline phosphatase, total bilirubin levels and hazard of death, but age, PQ dose, creatine kinase isoenzyme, creatine kinase, white blood cell count, neutrophil percentage and lymphocyte percentage were associated with mortality in patients with PQ poisoning. The occurrence of liver injury within 48 h after PQ poisoning was a risk factor for mortality, and such liver injury was likely of a hepatocellular nature. Age, PQ dose, creatine kinase isoenzyme and white blood cell count were positively correlated with mortality, while creatine kinase, percentage of neutrophils and lymphocytes were inversely correlated.

An International Study of Factors Affecting Variability of Dosimetry Calculations, Part 3: Contribution from Calculating Absorbed Dose from Time-Integrated Activity.

Image-based dosimetry-guided radiopharmaceutical therapy has the potential to personalize treatment by limiting toxicity to organs at risk and maximizing the therapeutic effect. The 177Lu dosimetry challenge of the Society of Nuclear Medicine and Molecular Imaging consisted of 5 tasks assessing the variability in the dosimetry workflow. The fifth task investigated the variability associated with the last step, dose conversion, of the dosimetry workflow on which this study is based. Methods: Reference variability was assessed by 2 medical physicists using different software, methods, and all possible combinations of input segmentation formats and time points as provided in the challenge. General descriptive statistics for absorbed dose values from the global submissions from participants were calculated, and variability was measured using the quartile coefficient of dispersion. Results: For the liver, which included lesions with high uptake, variabilities of up to 36% were found. The baseline analysis showed a variability of 29% in absorbed dose results for the liver from datasets where lesions included and excluded were grouped, indicating that variation in how lesions in normal liver were treated was a significant source of variability. For other organs and lesions, variability was within 7%, independently of software used except for the local deposition method. Conclusion: The choice of dosimetry method or software had a small contribution to the overall variability of dose estimates.

Diagnostic Role of Non-Invasive Risk Scores in Prediction of Simple Steatosis versus Non-Alcoholic Steatohepatitis

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is currently considered one of the most common liver diseases in the Western world. NAFLD includes a spectrum of diseases from simple fatty liver disease, to non-alcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma (HCC). NASH, the critical stage in NAFLD progression, is the only bridge between NAFLD and liver cirrhosis, and its persistent existence has become one of the leading causes of liver cirrhosis and even HCC. Aim of the Work To assess the value of non-invasive risk scores in differentiation between simple steatosis and NASH Patients and Methods This was prospective cohort study, conducted Internal Medicine and Gastroenterology outpatient clinics and ward in Ain Shams University Hospitals, on 60 patients with NAFLD divided into 2 groups: (Group I): Patients with normal liver enzymes, (Group II): Patients with persistant elevation of liver enzymes, during a period of 6 months. Results There was statistically insignificant difference between the two studied groups and sex and age. There were 12 (40%) of the group I were males and 18 (60.0%) were females. There were 16(53.3%) of the group II were males and 14(46.7%) were females. The mean age of group I was 40.63 ± 10.53 SD with range (25.0 – 59.0). The mean age of group II was 40.83 ± 9.06SD with range (27.0 – 54.0). There was statistically significant difference between the two studied groups and weight, BMI and waist circumference. There was statistically insignificant difference between the two studied groups and height, DM and HTN. There was statistically significant difference between the two studied groups and ALT, AST, GGT, ALP, ALB and Platelets. There was statistically significant difference between the two studied groups and TC, HDL, LDL, TG and AST/ALT ratio. There was statistically insignificant difference between the two studied groups and FBG. There was statistically significant difference between the two studied groups and FLI, NFS, BARD, APRI, FIB-4 and Fibrosis score. There was statistically significant difference between the two studied groups and Ultrasound (Size, Findings and Fibrosis score). The mean size in group I was 10.03 ± 1.56 SD with range (8.0 – 12.0). The mean size in group II was 13.63 ± 1.22SD with range (12.0 – 16.0). Conclusion A combination of Fibroscan, Fib-4, NFS, BARD and APRI provides a valuable non- invasive method in diagnosis of NASH patients, and this can eliminate the need for liver biopsy in patients without clear indication, BMI, platelet count, HDL cholesterol level, ALT level, and the AST/ALT ratio were independent predictors of NAFLD.

In-vitro hepatotoxic activity of mitragynine and paynantheine isolated from the leaves of Mitragyna speciosa Korth. (Kratom)

Mitragynine, a primary alkaloid found in kratom leaves has been reported to have a broad range of pharmacological and toxicological properties while its congener, paynatheine has comparatively less information available on these aspects. Mitragynine and its congener, paynantheine, were isolated from the ethanol kratom leaves extract using gravity column chromatography techniques. Our study evaluated the cytotoxicity potential of mitragynine and paynantheine on normal human liver cell line, HL-7702, and human hepatoma cell line, HepG2. Mitragynine exhibited a moderate inhibitory effect on the HepG2 cell line with IC50 value of 42.11 ± 1.31 μM in comparison with vinblastine (IC50: 15.45 ± 0.72 μM) while it showed non-cytotoxic properties towards the HL-7702 cell line with concentrations ranging below 200 μM. In contrast, paynantheine exhibited weak cytotoxic properties towards HepG2 and HL-7702 cell lines. Further comprehensive evaluations of both compounds are needed to establish more details on the cytotoxicity potential of kratom alkaloids.

In-vitro hepatotoxic activity of mitragynine and paynantheine isolated from the leaves of Mitragyna speciosa Korth. (Kratom)

Mitragynine, a primary alkaloid found in kratom leaves has been reported to have a broad range of pharmacological and toxicological properties while its congener, paynatheine has comparatively less information available on these aspects. Mitragynine and its congener, paynantheine, were isolated from the ethanol kratom leaves extract using gravity column chromatography techniques. Our study evaluated the cytotoxicity potential of mitragynine and paynantheine on normal human liver cell line, HL-7702, and human hepatoma cell line, HepG2. Mitragynine exhibited a moderate inhibitory effect on the HepG2 cell line with IC50 value of 42.11 ± 1.31 μM in comparison with vinblastine (IC50: 15.45 ± 0.72 μM) while it showed non-cytotoxic properties towards the HL-7702 cell line with concentrations ranging below 200 μM. In contrast, paynantheine exhibited weak cytotoxic properties towards HepG2 and HL-7702 cell lines. Further comprehensive evaluations of both compounds are needed to establish more details on the cytotoxicity potential of kratom alkaloids.