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Determination of beryllium and selenium in human urine and of selenium in human serum by graphite-furnace atomic absorption spectrophotometry.

For human urine beryllium (Be), each sample (500 microl) was diluted (1+1) with Nash reagent (containing 0.2% (v/v) acetylacetone and 2.0 M ammonium acetate buffer at pH 6.0) and then a 20-microl volume of Triton X-100 (0.4%, v/v) aqueous solution was added. An aliquot (10 microl) of the diluted urine mixture was introduced into a graphite cuvette and was atomized according to a temperature program. The method detection limit (MDL, 3sigma) for Be was 0.37 microg/l in the undiluted urine sample and the calibration graph was linear up to 65.0 microg/l. Calibration graphs were prepared by the standard addition method. Accuracies of 98.6-102% were obtained when testing standard reference material (SRM 2670) freeze dried human urine samples. Precision (relative standard deviation, RSD) for urine Be was < or = 2.3% (withinrun, n = 5) and was < or = 3.0% (between-run, n = 3). For human urine and serum selenium (Se), samples (100 microl) were diluted with HNO3 (0.2%, v/v) to make a (1+1) dilution for urine analysis or a (1+4) dilution for serum analysis. An additional aliquot (10 microl) of Triton X-100 (0.1%, v/v) was added to each 200 microl of (1+1) diluted urine (or 20 microl of the Triton X-100 was added to each 500 microl of (1+4) diluted serum) sample. After the diluted sample mixture (10 microl) was introduced into a graphite cuvette, the corresponding chemical modifier (10 microl, containing Ni2+ + Pd + NH4NO3 in HNO3 (0.2%, v/v)) was added to it and the mixture was atomized. The MDL (3sigma) for Se in urine and in serum was 4.4 and 21.4 microg/l in undiluted sample, respectively, and the calibration graphs were linear up to 150 and 400 microg/l. Accuracies of urine Se were 98.9 - 99.4% by testing SRM 2670 (NIST) urine standards with RSD (between-run, n = 3) within 2.9%; and that of serum Se was 97.2% when testing a certified second-generation human serum (No. 29, #664) with RSD (between-run, n = 3) of 1.4%. The proposed method can be applied easily, directly, and accurately to the measurement of Be and Se in real samples (including six urine Se and four serum Se from patients of Blackfoot Disease in Taiwan).

Beryllium↗

Modeling flow and nitrate fate at catchment scale in Brittany (France).

In the intensive pig-farming (Sus scrofa) area of Brittany (western France), many surface and subsurface water resources are contaminated by nitrate (NO3) with concentrations that chronically exceed the European Community 50 mg L(-1) drinking standard. To ensure sustainable water supply, the fate of NO3 must be considered in both surface water and ground water. The fate of N was investigated in a Britain catchment, the Coët-Dan watershed, with an integrated management tool: the hydrological SWAT model coupled with the ground water model MODFLOW, and its companion contaminant and solute transport model MT3DMS. The model was validated with respect to water quantity during a 6-yr period and for the NO3 concentration during a 44-mo period, at two gauging stations in the catchment. The coupled models reproduced accurately the measurements. At the basin outlet, the Nash-Sutcliffe coefficients were 0.88 for monthly flow for the entire period and 0.87 for monthly N load. Alternative scenarios were simulated and showed potential benefits of decreasing manure application from 210 to 170 kg N ha(-1) as required by the European Commission Nitrates Directive.

Animals↗

Field evaluation of a model for predicting nitrogen losses from drained lands.

The N simulation model, DRAINMOD-N II, was field-tested using a 6-yr data set from an artificially drained agricultural site located in eastern North Carolina. The test site is on a nearly flat sandy loam soil which is very poorly drained under natural conditions. Four experimental plots, planted to a corn (Zea mays)-wheat (Triticum aestivum L.)-soybean (Glycine max.) rotation and managed using conventional and controlled drainage, were used in model testing. Water table depth, subsurface drainage, and N concentration in drain flow were measured and meteorological data were recorded continuously. DRAINMOD-N II was calibrated using the data from one plot; data sets from the other three plots were used for model validation. Simulation results showed an excellent agreement between observed and predicted nitrate-nitrogen (NO(3)-N) losses in drainage water over the 6-yr period and a reasonable agreement on an annual basis. The agreement on a monthly basis was not as good. The Nash-Sutcliffe modeling efficiency (EF) for monthly predictions was 0.48 for the calibration plot and 0.19, 0.01, and -0.02 for the validation plots. The value of the EF for yearly predictions was 0.92 for the calibration plot and 0.73, 0.62, and -0.10 for the validation plots. Errors in predicting cumulative NO(3)-N losses over the 6-yr period were remarkably small; -1.3% for the calibration plot, -8.1%, -2.8%, and 4.0% for the validation plots. Results of this study showed the potential of DRAINMOD-N II for predicting N losses from drained agricultural lands. Further research is needed to test the model for different management practices and soil and climatological conditions.

Agriculture↗

Application of WetSpa model for assessing land use impacts on floods in the Margecany-Hornad watershed, Slovakia.

The spatially distributed hydrologic model WetSpa combines elevation, soil and land use data within GIS, to predict flood hydrographs and spatial distribution of hydrologic characteristics in a watershed. The model is applied to the Margecany-Hornad river basin (1131 km2) in Slovakia. Daily hydrometeorological data from 1991-2000, including precipitation data from nine stations, temperature data from four stations and evaporation data measured at one station are used as input to the model. Three base maps, i.e. DEM, land use and soil type are prepared in GIS form, using 100 x 100 m cell size. Results of the simulations show good agreement between calculated and measured hydrographs. The model predicts the daily/hourly hydrographs with 75-80% accuracy according to the Nash-Sutcliff criteria. For assessing the impact of land use changes on floods, the calibrated model is applied for a reforestation scenario, which considers a 50% increase of forest areas. The model results show that the reforestation scenario decreases the peak discharge by 12%. Investigation of peak discharges from the whole simulation period, shows that the scenario results are reduced by 18% on average, while for small discharges the reduction is even about 34%. The time to peak of the simulated hydrograph of the reforestation scenario is 20 hours longer than for the present land use.

Disasters↗

Brachial-ankle pulse wave velocity in Japanese university students.

OBJECTIVE: Pulse wave velocity (PWV) correlates well with arterial distensibility and stiffness and is a useful non-invasive index to assess arteriosclerosis. The present study was conducted to evaluate the validity of noninvasive brachial-ankle PWV (baPWV) measurements in overweight young adults. METHODS: Three hundred and fifty-three students were voluntarily enrolled (mean age: 20+/-2, 93 women and 260 men). The subjects were divided into three groups: normal (18.5 < or = body mass index (BMI) <25 n = 120), overweight (25 < or = BMI <30 n = 164) and obese (BMI > or = 30, n = 69). The baPWV was measured using volume-plethymographic apparatus. RESULTS: Hypertension and hyperlipidemia were diagnosed in one-third of the subjects of the obese group and nonalcoholic fatty liver disease (NAFLD) was diagnosed in 64% of the obese group. The baPWV in male subjects was significantly higher in the obese group than in the overweight group and in the males with NAFLD than in those without NAFLD. The stepwise linear regression analysis showed that PWV was significantly associated with mean blood pressure (p < 0.001) and gamma-GTP (p = 0.03). CONCLUSION: Mean blood pressure was a powerful determination for baPWV in the university students. BaPWV may be useful to predict the initial stage of arteriosclerosis and conceivably NAFLD including nonalcoholic steatohepatitis (NASH) in obese young adults.

Adult↗

Current pharmacological treatment of nonalcoholic fatty liver.

Nonalcoholic fatty liver disease (NAFLD) is a frequent and potentially progressive chronic liver disease that occurs in subjects who do not abuse alcohol. NAFLD is often associated with obesity, metabolic syndrome and insulin resistance and its more aggressive form, nonalcoholic steatohepatitis (NASH) is a major cause of cryptogenic cirrhosis. NAFLD/NASH are commonly detected because of elevated serum aminotransferase levels, ultrasonographic fatty liver and, at liver histology, steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Current management of NAFLD/NASH is largely conservative and includes diet regimen, aerobic exercise, and interventions towards the associated metabolic abnormalities. The main concern is therefore to decrease liver steatosis and its progression toward steatohepatitis and fibrosis, and the risk of "cryptogenic" cirrhosis. Among the most promising medications, weight reducing drugs, insulin sensitizers and lipid-lowering agents, antioxidants, bile salts, co-factors increasing the mitochondrial transport of fatty acids are being considered. Among them, thiazolidinediones are the most promising drug family that act by activating PPARgamma nuclear receptors and by regulating both microsomal and peroxisomal lipid oxidative pathways. Pharmacological treatment of obesity and probiotics should be considered as potential therapeutic options. In this review, after summarizing the general background on fatty liver, the most current and attractive pharmacological approaches to the problem of NAFLD/NASH are discussed.

Anti-Obesity Agents↗

Mechanisms of liver injury: an overview.

Liver cirrhosis, an end-result of a wide variety of the liver diseases, is a world wide health problem. Because of its unique organ system, i.e., portal blood supply, bile formation and enterohepatic circulation, drug metabolism system, and sinusoidal lining cells such as Kupffer, endothelial and stellate cells, the liver is a target of a variety of hepatotoxic insults. Current data suggest that hepatocyte apoptosis is an essential feature contributing to liver injury in a wide range of acute and chronic liver diseases. With an improved understanding of the pathophysiological role of apoptosis in liver diseases, we are now entering an era where regulation of liver cell apoptosis is becoming a therapeutic possibility. Inhibition of hepatocyte apoptosis using a variety of different strategies may be therapeutically beneficial in liver injuries, such as alcoholic hepatitis, non-alcoholic steatohepatitis (NASH), viral hepatitis, and cholestatic liver diseases. Considering the link between hepatocyte apoptosis and liver fibrosis, inhibition of hepatocyte apoptosis may also be an anti-fibrotic therapeutic strategy. Moreover, selective induction of apoptosis of activated stellate cells would be a unique approach to induce the resolution the phase of liver fibrosis. These concepts merit further clinical and basic investigation.

Animals↗

[Elevated aminotransferse levels--diagnostic approach].

INTRODUCTION: Aminotransferase levels are a sensitive indicator of liver cell injury and is frequently used to identify patients with liver diseases such as hepatitis. Both aminotransferases are normally present in serum at low levels, usually less than 30 U per liter. Although these enzymes are present in tissues throughout the body, they are most often elevated in patients with liver diseases and may reflect liver injury. Raised aminotransferase levels of unknown origin are common problem in clinical practice. Serum alanine aminotransferase (ALT) activity, the variable most commonly measured to assess hepatic disease, fails to identify many patients with hepatic injury. On the other hand, elevated ALT level doesn't always confirm liver disease. The aim of this study was to show the most common reasons for elevated aminotransferase levels. MATERIAL AND METHODS: The study included 27 patients with elevated ALT. All of them were followed-up for six months before liver biopsy was performed. All patients underwent routine laboratory tests and ultrasound of the abdomen. RESULTS: We found that four patients had a nonalcoholic steatohepatitis (NASH), four patients had chronic hepatitis of unknown etiology, two of them had autoimmune hepatitis, four had mild lobular hepatitis (three of them unresolved acute hepatitis, one of them had nodular regenerative hyperplasia), six patients had normal results, and three had no specific changes. CONCLUSION: Elevated ALT level doesn't always mean that there is a liver disease. If aminotransferase levels are persistently more than twice the normal value, a biopsy is recommended. Although results of biopsy are unlikely to lead to a diagnosis or to changes in management, they often provide reassurance to the patient and the physician to exclude serious pathology.

Adult↗

Supplementation of growing cattle grazing warm-season grass with proteins of various ruminal degradabilities.

This study was conducted to determine in situ ruminal protein degradation and animal responses to ruminally degraded and escape protein supplementation of warm-season grass. Cattle grazed a mixed stand of primarily big bluestem (Andropogon gerardii Vitman) and switchgrass (Panicum virgatum L.) with some indiangrass (Sorghastrum nutans [L.] Nash) from the 1st wk of June to the 3rd wk of August. In 1987, 72 yearling steers (286 kg) were allotted randomly to three treatments: energy control (cornstarch-molasses mixture) or energy control plus .1 or .2 kg.animal-1.d-1 of escape protein. The total amount of a supplement fed per day was 1 kg. In 1988, 90 yearling heifers (240 kg) were allotted to five treatments: negative control (no supplement), energy control, energy control plus .14 kg.animal-1.d-1 of escape protein, energy control plus .18 kg.animal-1.d-1 of ruminally degraded protein, or .36 kg.animal-1.d-1 of protein supplied by a combination of the two protein sources. The total amount of a supplement fed per day was 1.7 kg. During 1987, the .2-kg level of escape protein produced the greatest gains (P < .10). In 1988, gains did not differ between the control and escape protein treatments. Ruminally degraded protein tended (P = .12) to increase gains (.09 kg/d) compared with the energy control. The combination treatment supported .13 kg/d more ADG (P < .10) than the negative and energy controls and the escape protein treatment. Ruminal ammonia concentrations in unsupplemented steers were low, with few values > 5 mg/dL. Based on in situ measurements, 42 to 54% of the forage protein escaped ruminal degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.

INTRODUCTION: R-loops, RNA-DNA hybrid structures with a displaced single-stranded DNA loop, are key regulators of transcriptional control, chromatin architecture, and genome stability and have emerging roles in inflammatory signaling. However, the relationship between R-loop abundance and strongly modulated inflammatory effector genes in metabolic inflammation and influenza virus infection remains underexplored. METHODS: We performed a locus-centric integrative analysis combining robust differentially expressed genes (DEGs) from multiple inflammatory and infection-related murine and human transcriptomic disease models with experimentally validated multi-cell R-loop annotations from the reference atlas RLoopBase. Our correlation framework evaluated the directional relationship between R-loop abundance and inflammatory gene expression rather than assuming disease-sample-matched R-loop measurements. We further analyzed R-loop regulatory proteins, NRF2-associated R-loop regulators, and overlaps between R-loop regulators and CRISPRi-identified mitochondrial and cellular reactive oxygen species (ROS) regulators. RESULTS: In angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice, a model of abdominal aortic aneurysm (AAA), genomic regions encoding the top significantly upregulated genes exhibited significantly fewer R-loops than those encoding downregulated genes at days 14 and 28. Similarly, in atherosclerotic ApoE-/- mice fed a high-fat diet for 32 and 78 weeks, upregulated genes were associated with fewer R-loops than downregulated genes. Reduced R-loop abundance was also observed in genomic regions encoding the top significantly upregulated genes in liver tissues from patients with non-alcoholic steatohepatitis (NASH), as well as in monosodium urate (MSU)-stimulated lymphatic endothelial cells (LECs) and influenza virus-infected human umbilical vein endothelial cells (HUVECs). R-loop regulatory proteins upregulated during metabolic inflammation were enriched in immune and inflammatory pathways. NRF2 was identified as a regulator of 27 R-loop regulatory proteins, including 10 positively and 17 negatively regulated proteins. Furthermore, 54 R-loop regulatory proteins overlapped with CRISPRi-identified mitochondrial and cellular ROS regulators, suggesting potential reciprocal regulation between R-loop homeostasis and ROS signaling. Disease-associated changes in pro-ROS and anti-ROS R-loop regulatory proteins further linked R-loop regulation to inflammatory and oxidative stress pathways. DISCUSSION: These findings identify reduced R-loop abundance at genomic regions encoding strongly upregulated inflammatory genes as a shared feature across multiple models of metabolic inflammation and influenza virus infection. The results further suggest that immune-associated R-loop regulatory proteins and the NRF2-ROS axis may contribute to R-loop remodeling during inflammatory disease. This integrative framework provides new insight into the potential role of R-loops and ROS-sensitive R-loop regulators in inflammatory and metabolic diseases and identifies candidate pathways for future mechanistic investigation and therapeutic targeting.

R-loop regulatory proteins↗

AI-driven diagnostic and prognostic models for metabolic dysfunction-associated steatotic liver disease: insights from clinical, imaging, and multi-omics studies-a scoping review.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease around the world, affecting 33.6% of the adult population (95% CI: 28.1%-39.5%; I 2&#x2009;=&#x2009;99.9%), or roughly one in three. The extent of the liver damage is variable, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), cirrhosis and hepatocellular carcinoma (HCC). Early diagnosis is essential to prevent serious liver damage. Traditional diagnostic techniques such as liver biopsy, imaging, and biomarker testing are all invasive, costly, reduced sensitive to early-stage disease, and they also have variability among observers. Modern diagnostic and prognostic approaches based on the principles of Artificial Intelligence (AI) and specifically on machine learning (ML) and deep learning (DL) have enabled multimodal approaches integrating clinical, imaging and molecular data. This scoping review conducted per PRISMA-ScR guidelines, synthesizes findings from 73 studies (search window 2020-2026) across three dimensions: clinical data driven models, imaging-based classifiers (ultrasound, CT and MRI), and multi-omics (genomics, transcriptomics and proteomics) techniques. Moreover, emergence of models such as U-Net and LiverNet 2.x, classification models like DeepLiverNet and BiLSTM models, as well as transformer frameworks and the identification of biomarkers models are also described. This study also investigates challenges such as data heterogeneity, data interpretability, fairness and real-world clinical application. Finally, important areas of research opportunities and future directions are highlighted to present a developing clinically applicable, explainable and ethical AI solutions to manage MASLD.

MASLD↗

Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases.

AIM: To determine whether parenchymal cells or hepatic cytochrome P450 protein was changed in chronic liver diseases, and to compare the difference of CYP3A4 enzyme and its gene expression between patients with hepatic cirrhosis and obstructive jaundice, and to investigate the pharmacologic significance behind this difference. METHODS: Liver samples were obtained from patients undergoing hepatic surgery with hepatic cirrhosis (n=6) and obstructive jaundice (n=6) and hepatic angeioma (controls, n=6). CYP3A4 activity and protein were determined by Nash and western blotting using specific polychonal antibody, respectively. Total hepatic RNA was extracted and CYP3A4cDNA probe was prepared according the method of random primer marking, and difference of cyp3a4 expression was compared among those patients by Northern blotting. RESULTS: Compared to control group, the CYP3A4 activity and protein in liver tissue among patients with cirrhosis were evidently reduced. (P<0.01) Northern blot showed the same change in its mRNA levels. In contrast, the isoenzyme and its gene expression were not changed among patients with obstructive jaundice. CONCLUSION: Hepatic levels of P450s and its CYP3A4 isoform activity were selectively changed in different chronic liver diseases. CYP3A4 isoenzyme and its activity declined among patients with hepatic cirrhosis as expression of cyp3a4 gene was significantly reduced. Liver's ability to eliminate many clinical therapeutic drug substrates would decline consequently. These findings may have practical implications for the use of drugs in patients with cirrhosis and emphasize the need to understand the metabolic fate of therapeutic compounds. Elucidation of the reasons for these different changes in hepatic CYP3A4 may provide insight into more fundamental aspects and mechanisms of imparied liver function.

Adult↗

Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes.

AIM: Hepatic cytochrome P450 isoenzymes constitute a superfamily of hemoproteins that play a major role in the metabolism of endogenous compounds and in the detoxification of xenobiotic molecules. P450 3A4 is one of the most important forms in human being, and mediates the metabolism of around 70 % of therapeutic drugs and endogenous compounds. Propofol, a widely used intravenous anesthetic drug, is known to inhibit cytochrome P450 activities in isolated rat hepatocytes. The goal of this study was to evaluate the potential efficacy of propofol on P450 3A4 in a dose-dependent manner to understand its drug-drug interaction. METHODS: Hepatocytes were isolated from liver specimens from hepatic angioma patients undergone hepatic surgery. Primary incubated hepatocytes were treated with 0, 0.01, 0.05, 0.1, 0.5, and 1.0 mM propofol for 24 hours. P450 3A4 activity was measured with Nash's colorimetry. The protein expression was assessed by Western blot analysis. RESULTS: A dose-dependent inhibitory effect of propofol was observed in cytochrome P450 3A4 activity. A minimal dosage of propofol (0.01 mM) induced a significant inhibition of P450 3A4 activity, although its regular dosages (0.01-0.1 mM) showed no inhibitory effect on the cellular protein expression of P450 3A4. CONCLUSION: Propofol may be a potential CYP3A4 inhibitor as this anesthetic can inhibit isoenzyme activity significantly and reduce the metabolic rate of CYP3A4 substrates. This inhibition occurs at post-expression level, and concentration of propofol used clinically does not affect CYP3A4 protein expression. propofol may thus induce drug interaction of cytochrome P450 3A4 activity at the dosage used clinically.

Aryl Hydrocarbon Hydroxylases↗

[Effects of kaempferol and quercetin on cytochrome 450 activities in primarily cultured rat hepatocytes].

OBJECTIVE: To observe the effects of kaempferol and quercetin on the activity of cytochrome P450 in rat hepatocytes. METHODS: Primarily cultured rat hepatocytes were exposed to kaempferol or quercetin in concentrations of 0.1, 1, 10 micromol/L for 12 h, 24 h and 48 h. Hepatocytes CYP isoemzymes-erythromycin N-demethylase (ERND) and aminopyrine N-demethylase (ADM) activities were determined by Nash methods. Erythromycin (10 micromol/L) was used as positive control and DMSO(0.1%) as solvent control. RESULTS: Kaempferol and quercetin inhibited ENRD activity in a dose-and time-dependent manner. In dose-response study, the ENRD activities in kaempferol (0.1,1 and 10 micromol/L) treated groups were (0.088+/-0.008), (0.074+/-0.006) and (0.041+/-0.003)micromol/(mg.min(-1)), respectively. ENRD activity in quercetin treated groups at the same concentrations were (0.082+/-0.007), (0.063+/-0.007) and (0.034+/-0.005) micromol/(mg.min(-1)), respectively. In time-courses study, the ENRD activity exposed to 10 micromol/L kaempferol or quercetin for 12 h and 48 h were (0.053+/-0.006) and (0.037+/-0.007) micromol/(mg.min(-1)), or (0.067+/-0.005) and (0.032+/-0.004) micromol/(mg.min(-1)). ADM activity was inhibited only by kaempferol in 10 mol/L at 24 h, but was not significantly altered by quercetin at any concentration tested. CONCLUSION: In the present condition, kaempferol and quercetin act as potential CYP3A4 inhibitors as they can significantly inhibit ENRD in primarily cultured rat hepatocytes.

Aminopyrine N-Demethylase↗

Selective efficacy of culture media recommended for isolation and enumeration of Fusarium spp.

Selective culture media, such as Nash and Snyder medium (NS), dichloran-chloramphenicol peptone agar (DCPA), modified Czapek-Dox agar (MCz), Czapek Dox iprodione dichloran agar (CZID), potato dextrose iprodione dichloran agar (PDID), or malachite green agar (MGA 2.5), have been developed for isolating and enumerating Fusarium spp. from natural samples. However, some of these culture media are not very selective because they allow the growth of many other fungal species. In this study, a comparison of the selective efficacy of these culture media, using different strains of Fusarium spp. (F. anthophilum, F. culmorum, F. dlamini, F. graminearum, F. napiforme, F. nygamai, F. oxysporum, F. proliferatum, F. semitectum, F. solani, F. subglutinans, and F. verticillioides) and natural samples has been carried out. Among the six recommended selective culture media assayed, no statistical differences were detected in colony counts of the Fusarium spp. strains tested, although the colony diameters in MGA 2.5 were significantly lower than in NS, MCz, DCPA, CZID, and PDID media. With natural samples, MGA 2.5 performs as a potent selective medium for Fusarium spp., whereas the other recommended selective media allow the growth of many other different fungal species including Zygomycetes and yeasts.

Colony Count, Microbial↗

The Triad of NF-&#x3ba;B, HIF-1&#x3b1;, and Oxidative Stress in Hepatocellular Carcinoma: Pathogenesis, Clinical Challenges, and Therapeutic Potential of CIGB-552 in Liver Transplantation.

Hepatocellular carcinoma (HCC) represents a formidable oncological challenge characterized by complex molecular pathogenesis and limited therapeutic outcomes, particularly in the context of liver transplantation. As the sixth most commonly diagnosed cancer and the third leading cause of cancer-related mortality worldwide, HCC poses significant clinical challenges that demand innovative therapeutic approaches. Central to HCC development and progression is a pathogenic triad comprising nuclear factor-kappa B (NF-&#x3ba;B), hypoxia-inducible factor-1&#x3b1; (HIF-1&#x3b1;), and oxidative stress-three interconnected pathways that drive inflammation, angiogenesis, metabolic reprogramming, and cell survival. This comprehensive review examines the molecular mechanisms underlying this triad in HCC pathogenesis across different etiological contexts, including viral hepatitis and non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). We critically analyse the unique clinical challenges posed by HCC in liver transplantation recipients, particularly the paradoxical requirement for immunosuppression alongside antitumor immunity, and constraints surrounding immunotherapy application. Furthermore, we present CIGB-552, a novel peptide therapeutic targeting COMMD1 (Copper Metabolism MURR1 Domain-containing protein 1), as a promising dual-function agent capable of simultaneously disrupting the pathogenic triad through NF-&#x3ba;B inhibition, HIF-1&#x3b1; suppression, and strategic modulation of oxidative stress via SOD1 regulation. The multimodal mechanism of CIGB-552 offers a theoretically rational therapeutic approach for HCC management in both pre-transplant and post-transplant settings. Clinical validation in the transplantation setting is required.

Humans↗

Transfer factor for the lung, airway obstruction and hyperinflation in chronic bronchitis and emphysema.

The interrelationships of breath holding lung transfer factor (TCO) and transfer coefficient (KCO) with ventilatory obstruction (FEV1.0) and FEV1.0/VC) and hyperinflation (RV and RV/TLC) were studied in 37 patients with chronic nonspecific lung disease with a FEV1.0 of 1.5 litre or less classified as "bronchitic", "emphysematous" or "intermediate" according to Nash, Briscoe and Cournand (1965). No relationships could be found between TCO and airway obstruction or hyperinflation. KCO tended to decrease as RV increased (r=-0.26) and was weakly related to the FEV1.0/VC ratio in "intermediate" (r=0.34) and "emphysema" (r=0.29) patients but these relationships were nonsignificant.

Adult↗

Demethylation capacity of human fetal adrenal mitochondrial cytochrome P-450 in vitro.

AIM: To explore the capacity and characteristics of adrenal mitochondria to metabolize xenobiotics in vitro in human fetus. METHODS: Subcellular fractions of fetal adrenal were prepared by differential centrifugation. Mitochondrial P-450 system was proved by spectral analyses and SDS-PAGE. The formaldehyde formation contents were measured with Nash reagent. RESULTS: The erythromycin N-demethylation linearly increased in the protein concentration (1-4 mg)- and incubation time (10-30 min)-dependent manners. A typical concentration-effect relationship appeared with erythromycin 0.067-1 mmol.L-1 and a positive correlation (r = 0.641, P < 0.05) existed between erythromycin N-demethylation and gestation months. The N-demethylation values (nmol.s-1/g protein) of erythromycin (2.7 +/- 0.8), benzfetamine (1.1 +/- 0.5), and aminophenazone (0.9 +/- 0.4) in mitochondria were 89% (P > 0.05), 162% (P < 0.01), and 62% (P < 0.01), respectively, of those in microsomes. There was correlation between mitochondria and microsomes in the N-demethylation of erythromycin (r = 0.708, P < 0.05) and benzfetamine (r = 0.707, P < 0.05). Troleandomycin stimulated erythromycin N-demethylation in adrenal mitochondria as well as in adrenal and liver microsomes in vitro. CONCLUSION: Fetal adrenal mitochondria, with multiple P-450 isoforms and greater capacity of demethylation, play a role in drug-metabolism during fetal development.

Adrenal Glands↗