• Cell proliferation
• Diffuse large B-cell lymphoma
• LDHA
• Signaling pathway
• Tumor metabolism

• Lymphoma, Large B-Cell, Diffuse/pathology
• Lymphoma, Large B-Cell, Diffuse/metabolism
• Lymphoma, Large B-Cell, Diffuse/enzymology
• Lymphoma, Large B-Cell, Diffuse/genetics
• Humans
• L-Lactate Dehydrogenase/metabolism
• L-Lactate Dehydrogenase/genetics
• Cell Proliferation
• Cell Line, Tumor
• Isoenzymes/genetics
• Isoenzymes/metabolism
• STAT5 Transcription Factor/metabolism
• Apoptosis
• Cell Movement
• Male
• Gene Expression Regulation, Neoplastic
• Leukocytes, Mononuclear/enzymology
• Leukocytes, Mononuclear/metabolism
• Biomarkers, Tumor/metabolism
• Neoplasm Proteins/metabolism

• Grant #ZR2023MH157 the natural science foundation of Shandong Province of China

• Bullous pemphigoid
• Diacron-reactive oxygen metabolites
• Dibromotyrosine
• Oxidative stress
• ROS

• HCC recurrence
• mechanism
• postoperative recurrence
• surgical stress
• tumor microenvironment

• Humans
• Carcinoma, Hepatocellular/drug therapy
• Liver Neoplasms/drug therapy
• Tumor Microenvironment
• Neoplasm Recurrence, Local

• FIB-4 index
• NAFLD fibrosis score
• hepatocellular carcinoma
• non-viral hepatitis
• risk factor

• Emprint
• ablation volume
• blood perfusion
• hyperthermia
• microwave ablation

• biological antioxidant potential test
• derivatives of reactive oxygen metabolites test
• diffuse large B-cell lymphoma
• non-Hodgkin's lymphoma
• oxidative stress

• glucose
• hepatocellular carcinoma
• lymphocyte
• prognosis
• sorafenib
• survival

• epigallocatechin gallate
• green tea
• multiple parallel hits
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis
• oxidative stress
• reactive oxygen species
• redox homeostasis

• 200006276 Wong's Donation
• 17152116 Research Grant Council, HKSAR
• 15162961 Food and Health Bureau, HKSAR
• 16172751 Food and Health Bureau, HKSAR

With the increasing prevalence of obesity and diabetes in most countries, the increase in hepatocellular carcinoma (HCC) associated with these factors has recently become a serious healthcare problem. HCC can often emerge in the non-cirrhotic liver among obese patients, and it might suggest that the conventional surveillance strategies for HCC, which is mainly targeted at cirrhotic patients with hepatitis B or C virus, might be insufficient in the overnutrition era. We tried to extract factors that affect recurrence-free survival in patients with non-viral HCC, among obesity and diabetes factors, together with the established recurrence risk factors, using a decision-tree analysis.

We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted risk factors was evaluated using the Kaplan–Meier method and the Cox proportional hazards model. The decision-tree analysis extracted three factors—visceral adipose tissue (VAT) index (VATI; <71 and ≥71 cm²/m²), which was the cross-sectional areas of VAT on the computed tomographic image at the umbilical level, normalized by the square of the height, fasting immunoreactive insulin (FIRI; <5.5 and ≥5.5 µU/mL), and alpha-fetoprotein (AFP; <11 and ≥11 ng/mL). The Cox proportional hazards model showed that VATI (hazard ratio (HR): 2.556, 95% confidence interval (CI): 1.191–5.486, p = 0.016), FIRI (HR: 3.149, 95% CI: 1.156–8.575, p = 0.025), and AFP (HR: 3.362, 95% CI: 1.550–7.288, p = 0.002) were all independent risk factors for HCC recurrence. Non-B non-C HCC patients with a higher VATI (≥71 cm²/m²) or higher FIRI (≥5.5 µU/mL) and AFP (≥11 ng/mL) if VATI was <71 cm²/m² are prone to recurrence after curative treatment.

• fasting immunoreactive insulin
• non-viral hepatocellular carcinoma
• recurrence risk factor
• visceral adipose tissue

• HCC
• cHCC-CCA
• iCCA
• inflammation
• oxidative stress

• body composition
• hepatocellular carcinoma
• prognostic factor
• skeletal muscle
• sorafenib
• subcutaneous fat mass

There are several studies on oxidative stress of Autism Spectrum Disorder (ASD), but in these cases there is no study to measure oxidative stress and antioxidant capacity at the same time or studies considering childhood development. Therefore, this study comprehensively assessed the level of oxidative stress in ASD children by simultaneously measuring reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). The subjects were Japanese, 77 typical development (TD) children, 98 ASD children, samples were plasma. The subjects were divided into age groups: toddlers/preschool age (2–6 years) and school age (7–15 years), to compare the relationships among the d-ROMs levels and BAP/d-ROMs ratios. Furthermore, the correlations between the Parent-interview ASD Rating Scales (PARS) scores and the measured values were analyzed. The levels of d-ROMs were significantly higher in the ASD (7–15 years) than in TD (7–15 years). The PARS scores were significantly higher in the ASD and were significantly correlated with d-ROMs levels. These results suggested that d-ROMs and BAP/d-ROMs ratios could be objective, measured indicators that could be used in clinical practice to assess stress in ASD children.

• Adolescent
• Autism Spectrum Disorder/metabolism
• Child
• Child, Preschool
• Female
• Humans
• Japan
• Male
• Oxidation-Reduction
• Oxidative Stress
• Reactive Oxygen Species/metabolism

• cancer cachexia
• hepatocellular carcinoma
• sarcopenia
• skeletal muscle
• sorafenib
• subcutaneous fat

Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan–Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM (p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 μU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM (p = 0.009), and there was no significant difference between those groups with DM (p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment.

• Hepatocellular carcinoma
• diabetes mellitus
• homeostasis model assessment-insulin resistance (HOMA-IR)
• insulin resistance
• recurrence risk

• Animals
• Carbohydrate Metabolism
• Humans
• Lipid Metabolism
• Liver/metabolism
• Liver/pathology
• Liver Diseases/metabolism
• Liver Diseases/pathology

The outcome prediction of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) was classically established using various macromorphological factors and serum alpha-fetoprotein levels prior to LT. However, other biomarkers have recently been reported to be associated with the prognosis of HCC patients undergoing to LT. This review summarizes clinical data on these new biomarkers. High blood levels of malondialdehyde, total antioxidant capacity, caspase-cleaved cytokeratin-18, soluble CD40 ligand, substance P, C-reactive protein, and vascular endothelial growth factor, increased neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in blood, high peripheral blood expression of human telomerase reverse transcriptase messenger ribonucleic acid, and high HCC expression of dickkopf-1 have recently been associated with decreased survival rates. In addition, high blood levels of des-gamma-carboxy prothrombin, and high HCC expression of glypican-3, E-cadherin and beta-catenin have been associated with increased HCC recurrence. Additional research is necessary to establish the prognostic role of these biomarkers in HCC prior to LT. Furthermore, some of these biomarkers are also interesting because their potential modulation could help to create new research lines for improving the outcomes of those patients.

• Liver transplantation
• Hepatocellular carcinoma
• Biomarkers
• Outcome
• Survival
• Recurrence
• Genomic

• Antigens, CD/metabolism
• Antioxidants/chemistry
• Biomarkers, Tumor/analysis
• C-Reactive Protein/metabolism
• CD40 Ligand/metabolism
• Cadherins/metabolism
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/surgery
• Caspases/metabolism
• Glypicans/metabolism
• Humans
• Intercellular Signaling Peptides and Proteins/metabolism
• Keratin-18/chemistry
• Liver Neoplasms/diagnosis
• Liver Neoplasms/mortality
• Liver Neoplasms/surgery
• Liver Transplantation
• Malondialdehyde/chemistry
• Prognosis
• Substance P/chemistry
• Telomerase/metabolism
• Vascular Endothelial Growth Factor A/metabolism
• beta Catenin/metabolism

• Chronic lymphocytic leukemia
• oxidative stress
• prognostication

• DNA adduct
• Oxidative stress
• hepatocarcinogenesis
• hepatocellular carcinoma
• prevention

To determine whether there was an association between serum total antioxidant capacity (TAC) levels prior to in liver transplantation (LT) for hepatocellular carcinoma (HCC) and 1-year LT mortality.

This observational retrospective single-centre study of patients with LT for HCC measured serum levels of TAC and malondialdehyde (as a biomarker of lipid peroxidation) before LT. The study endpoint was 1-year LT mortality.

This study included 142 patients who underwent LT for HCC. Patients who survived the first year (n = 127) had significantly lower aged liver donors, significantly higher serum TAC levels, and significantly lower serum malondialdehyde levels compared with the non-survivors (n = 15). Logistic regression analysis found that serum TAC levels (odds ratio [OR] 0.275; 95% confidence interval [CI] 0.135, 0.562) and the age of the LT donor (OR 1.050; 95% CI 1.009, 1.094) were associated with 1-year LT mortality. There was an inverse association between serum levels of TAC and malondialdehyde levels (rho = –0.22).

There was an association between low serum TAC levels prior to LT for HCC and mortality during the first year after LT. There was an inverse association between serum TAC levels and lipid peroxidation as measured by malondialdehyde levels.

• Serum total antioxidant capacity
• hepatocellular carcinoma
• liver transplantation
• mortality
• outcome

Obesity is a risk factor for the development of hepatocellular carcinoma (HCC). This study aimed to assess the influence of visceral fat on the recurrence of HCC after curative treatment. In 207 curative cases of HCC, the cross-sectional areas of visceral and subcutaneous fat mass on the computed tomographic image at the fourth lumbar vertebra were normalized by the square of the height to obtain the visceral fat mass index (VFMI) and the subcutaneous fat mass index (SFMI), respectively. Whether VFMI and SFMI contributed to recurrence of HCC and overall survival was analyzed using a Cox proportional hazards model. Increased VFMI was significantly associated with recurrence of HCC (P = 0.006), whereas SFMI was not (P = 0.502). When the patients were divided based on the optimal cut off value for VFMI (47.2 cm²/m²), obtained from maximally selected rank statistics to best predict the risk for recurrence, the higher VFMI group (n = 79) had more probability of recurrence than the lower VFMI group (n = 128) (log rank test, P = 0.002). There were significant differences in body mass index (P < .0001), SFMI (P < .0001), L3 skeletal muscle index (P < .0001), platelet count (P = 0.003), hemoglobin A1c (P < .0001), triglycerides (P = 0.004), serum leptin (P = 0.043), and underlying liver disease (P < .0001) between the groups. Neither VFMI (P = 0.689) nor SFMI (P = 0.117) significantly contributed to overall survival. VFMI, which is involved in obesity and its related metabolic disorders such as diabetes, hyperlipidemia, and adipokine imbalance, is an extremely promising indicator that can predict the risk of recurrence of HCC after curative treatment.

• hepatocellular carcinoma
• metabolic disorder
• obesity
• recurrence risk
• visceral fat volume

• hepatocellular carcinoma
• dna lesion
• biomarker
• antioxidant
• cancer prevention

• BAP test
• chronic lymphocytic leukaemia
• d-ROMs
• oxidative stress
• prognosis

We elucidate major pathways of hepatocarcinogenesis and accurate diagnostic metabolomic biomarkers of hepatocellular carcinoma (HCC) identified by contemporary HCC metabolomics studies, and delineate a model HCC metabolomics study design. A literature search was carried out on Pubmed for HCC metabolomics articles published in English. All relevant articles were accessed in full text. Major search terms included “HCC”, “metabolomics”, “metabolomics”, “metabonomic” and “biomarkers”. We extracted clinical and demographic data on all patients and consolidated the lead candidate biomarkers, pathways, and diagnostic performance of metabolomic expression patterns reported by all studies in tables. Where reported, we also extracted and summarized the metabolites and pathways most highly associated with the development of cirrhosis in table format. Pathways of lysophospholipid, sphingolipid, bile acid, amino acid, and reactive oxygen species metabolism were most consistently associated with HCC in the cited works. Several studies also elucidate metabolic alterations strongly associated with cirrhosis, with γ-glutamyl peptides, bile acids, and dicarboxylic acids exhibiting the highest capacity for stratifying cirrhosis patients from appropriately matched controls. Collectively, global metabolomic profiles of the referenced works exhibit a promising diagnostic capacity for HCC at a capacity greater than that of conventional diagnostic biomarker alpha-fetoprotein. Metabolomics is a powerful strategy for identifying global metabolic signatures that exhibit potential to be leveraged toward the screening, diagnosis, and management of HCC. A streamlined study design and patient matching methodology may improve concordance among metabolomic datasets in future works.

• Metabolomics
• Hepatocellular carcinoma
• Biomarkers
• Metabolic profiling
• Chromatography/mass spectrometry
• Noninvasive biomarkers
• Cirrhosis

Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA.

We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8.

We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV₁ (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025).

Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA.

• Adult
• Anti-Asthmatic Agents/therapeutic use
• Asthma/blood
• Asthma/immunology
• Asthma/physiopathology
• Biomarkers/blood
• Breath Tests
• Female
• Humans
• Interleukin-6/blood
• Interleukin-8/blood
• Leukocyte Count
• Male
• Middle Aged
• ROC Curve
• Reactive Oxygen Species/blood
• Respiratory Function Tests

• MDA
• hepatocellular carcinoma
• liver transplantation
• mortality
• outcome

• adiponectin
• astaxanthin
• liver tumorigenesis
• obesity
• oxidative stress

• JNK signaling
• cell-cycle
• extracellular ATP
• hepatocellular carcinoma
• purinergic receptors

• Adenosine Triphosphate/pharmacology
• Adolescent
• Adult
• Aged
• Blotting, Western
• Carcinoma, Hepatocellular/complications
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Cell Cycle/drug effects
• Cell Cycle/genetics
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cell Proliferation/genetics
• Cells, Cultured
• Cohort Studies
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Hepatitis C/complications
• Hepatitis C/genetics
• Hepatitis C/metabolism
• Humans
• Immunohistochemistry
• Liver Neoplasms/complications
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Receptors, Purinergic P2X3/genetics
• Receptors, Purinergic P2X3/metabolism
• Reverse Transcriptase Polymerase Chain Reaction
• Young Adult

• P30 DK056338 NIDDK NIH HHS
• R01 DK069558 NIDDK NIH HHS
• DK56338 NIDDK NIH HHS

Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves in hepatocellular carcinoma (HCC) patients and on the recurrence and prognosis of HCC. This study included 44 patients with any stage of HCC who underwent curative treatment at Gifu Municipal Hospital (Gifu, Japan) between 2006 and 2007. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Serum albumin levels (Pearson’s correlation coefficient; r = 0.3110, p = 0.0399), platelet counts (r = 0.4159, p = 0.0050), and prothrombin times (r = 0.3775, p = 0.0115) were significantly correlated with serum chemerin levels in patients with HCC, and they were inversely correlated with Child-Pugh scores (r = −0.3732, p = 0.0126), serum alanine aminotransferase levels (r = −0.3864, p = 0.0105), and total bilirubin levels (r = −0.4023, p = 0.0068). Among these variables, a multiple comparison test identified that platelet counts and total bilirubin levels were associated with serum chemerin levels (p < 0.0083). No significant correlation was found between serum chemerin levels and recurrence-free survival (p = 0.3691) or overall survival (p = 0.7916). In HCC patients, serum chemerin concentrations were correlated with liver functional reserves and platelet counts, but not with recurrence or prognosis.

• Aged
• Aged, 80 and over
• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/metabolism
• Chemokines/blood
• Female
• Humans
• Intercellular Signaling Peptides and Proteins
• Liver/metabolism
• Liver Neoplasms/blood
• Liver Neoplasms/diagnosis
• Liver Neoplasms/metabolism
• Male
• Middle Aged
• Platelet Count
• Prognosis

Metabolic syndrome (Mets), including diabetes and hypertension, increases the risk of colorectal cancer via the induction of chronic inflammation, acceleration of oxidative stress, and activation of the renin-angiotensin system. The present study examined the possible inhibitory effects of captopril, an angiotensin-converting enzyme (ACE) inhibitor and antihypertensive drug, on the development of azoxymethane (AOM)-induced colonic premalignant lesions, aberrant crypt foci (ACF), in SHRSP.Z-Lepr^fa/IzmDmcr (SHRSP-ZF) diabetic and hypertensive rats. Male 6-week-old SHRSP-ZF rats were administered two, weekly intraperitoneal injections of AOM (20 mg/kg body weight). Following the second injection, the rats received drinking water containing captopril (8 mg/kg/day) for two weeks. At sacrifice, captopril administration significantly lowered the blood pressure and reduced the total number and size of ACF compared with those observed in the untreated group. The serum levels of angiotensin-II and the expression levels of ACE and angiotensin-II type 1 receptor mRNA on the colonic mucosa decreased following captopril treatment. Captopril also reduced the urinary 8-hydroxy-2′-deoxyguanosine levels and the serum derivatives of reactive oxygen metabolites levels, both of which are oxidative stress markers, but increased the mRNA levels of catalase, an antioxidant enzyme, in the colonic epithelium. Moreover, the expression levels of tumor necrosis factor-α, interleukin-18, monocyte chemoattractant protein-1, inducible nitric oxide synthase, vascular endothelial growth factor and proliferating cell nuclear antigen mRNA in the colonic epithelium were decreased significantly following captopril administration. These observations suggested that captopril prevents the development of ACF by inhibiting renin-angiotensin system activation and attenuating inflammation and oxidative stress in SHRSP-ZF rats. Therefore, targeting Mets-related pathophysiological conditions, including renin-angiotensin system activation, may be an effective strategy to prevent colorectal carcinogenesis in patients with Mets, particularly those with hypertension.

• angiotensin-converting enzyme inhibitor
• colon carcinogenesis
• hypertension
• metabolic syndrome
• renin-angiotensin system

• Aging
• Autoimmune Diseases/metabolism
• Autoimmune Diseases/pathology
• Humans
• Mitochondria/metabolism
• Mitochondria/ultrastructure
• Mitochondrial Diseases/metabolism
• Mitochondrial Diseases/pathology
• Neoplasms/metabolism
• Neoplasms/pathology
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/pathology
• Oxidative Stress

• EGCG
• Inflammation
• Liver tumorigenesis
• Non-alcoholic steatohepatitis
• Oxidative stress

Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Lepr^fa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system.