Analysis of Immune and Inflammatory Microenvironment Characteristics of Noncancer End-Stage Liver Disease.

Chronic liver injury eventually progresses to cirrhosis and end-stage liver disease (ESLD), which are the leading causes of death in patients with liver disease worldwide. ESLD has a variety of etiologies and a complex pathogenesis. This study analyzed the characteristics of ESLD by studying the immune microenvironment and inflammatory microenvironment of ESLD caused by 4 noncancer diseases, including HBV-ALF, ALF, AILD, and AH. We collected transcriptome data from noncancer ESLD patients, collected liver tissue samples and blood samples from ESLD liver transplant patients, and analyzed the immune and inflammatory microenvironments in the liver and blood. The results showed that with the exception of HBV-induced ESLD, there were no significant differences in immune microenvironment scores among patients with ESLD caused by other noncancer diseases. Moreover, there were no significant differences in the inflammatory microenvironment in the liver and blood of patients with ESLD caused by the 4 noncancer diseases. Furthermore, we found that the cytokine, IL-15, could predict the prognosis of ESLD patients.

Diabetic Bone Marrow Cell Injection Accelerated Acute Pancreatitis Progression.

Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 µg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients (1 × 107cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively (p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection (p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups (p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately (p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC (p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis.

Progress and prospects of biomarkers in primary liver cancer (Review).

Tumor biomarkers are important in the early screening, diagnosis, therapeutic evaluation, recurrence and prognosis prediction of tumors. Primary liver cancer is one of the most common malignant tumors; it has high incidence and mortality rates and seriously endangers human health. The main pathological types of primary liver cancer include hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined HCC­cholangiocarcinoma (cHCC­CC). In the present review, a systematic outline of the current biomarkers of primary liver cancer is presented, from conventional blood biomarkers, histochemical biomarkers and potential biomarkers to resistance­associated biomarkers. The important relationships are deeply elucidated between biomarkers and diagnosis, prognosis, clinicopathological features and resistance, as well as their clinical significance, in patients with the three main types of primary liver cancer. Moreover, a summary of several important biomarker signaling pathways is provided, which is helpful for studying the biological mechanism of liver cancer. The purpose of this review is to provide help for clinical or medical researchers in the early diagnosis, differential diagnosis, prognosis and treatment of HCC.

Copper chelation by trientine dihydrochloride inhibits liver RFA-induced inflammatory responses in vivo.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. Radiofrequency ablation (RFA) is currently performed widely for managing HCC. RFA treatment causes damage around the ablation. Trientine dihydrochloride has been used to reduce the copper in liver. METHODS: The rats were treated with trientine dihydrochloride for 5 days before liver RFA. Liver function, copper concentration, inflammation biomarkers and MDA, SOD were analyzed after RFA treatment for 2 h, 2 and 5 days. RESULTS: The results indicated that trientine dihydrochloride reduced the copper in plasma and liver tissue significantly. And trientine dihydrochloride significantly inhibited RFA-induced inflammatory gene expression in liver. Similar inhibitory effects of trientine dihydrochloride were observed on ROS-induced malondialdehyde production in liver tissues. CONCLUSION: These results suggest that pre-treatment with the selective copper chelator trientine dihydrochloride can inhibit inflammatory response effectively during and after liver RFA in vivo. Chelation of copper to a lower level before liver RFA may be a novel strategy to prevent or ameliorate inflammatory responses in liver induced by RFA and to protect the parenchyma tissues in liver during and after RFA in HCC patients.

Qing Re Liang Xue Decoction Alleviates Hypercoagulability in Kawasaki Disease.

Objective. Kawasaki disease (KD) is a multisystemic autoimmune vasculitis. Intravenous immunoglobulin (IVIG) is the first-line treatment for KD. It is unclear whether traditional Chinese medicine (TCM) has an effect on KD. We aimed to observe the clinical efficacy of TCM on acute KD via serum interleukin-33 (IL-33) and tumor necrosis factor alpha (TNF-α) measurements. Methods. Thirty-one KD patients were treated with Qing Re Liang Xue decoction and Western medicine (integrative medicine treatment group), while 28 KD patients were treated with Western medicine only (Western medicine treatment group). Thirty patients were included in a febrile group and 28 healthy children were included in the control group. Clinical characteristics and laboratory findings were gathered and compared. Serum IL-33 and TNF-α levels were measured by multiplex Luminex assay. Results. The platelet count in the integrative medicine treatment group was significantly lower than that in the Western medicine treatment group. The integrative medicine group had a shorter fever duration and lower IL-33 and TNF-α levels than those in the Western medicine group, but there were no significant differences between the two KD groups after treatment. Conclusion. Qing Re Liang Xue decoction improved the hypercoagulable state of KD patients. Potential myocardial protective effects require further research.

[Association between genetic polymorphism of tumor necrosis factor and chronic severe hepatitis B in patients].

OBJECTIVE: To investigate the association between the single nucleotide polymorphisms (SNPs) of tumor necrosis factor (TNF-alpha) and chronic severe hepatitis B. METHODS: Single nucleotide polymorphisms (SNPs) at TNF-alpha promoter -238 G/A, -308 G/A, -857 C/T, -863 C/A were analyzed in 98 patients with chronic severe hepatitis B and 211 patients with chronic hepatitis B in Beijing You'an hospital; using polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR). RESULTS: The rate of TNF-alpha -308 A and -857 T were 34.1% vs 9.5%, 34.7% vs 21.8% in the two grapes; the frequencies distributions of alleles at TNF-alpha -308 G/A, -857 C/T were significantly higher in patients with chronic severe hepatitis B than those of patients with chronic hepatitis B (chi(2) = 59.01, P = 0.000; chi(2) = 11.59, P = 0.001); genotypes of -308 GA, -857 TT were significantly higher in patients with chronic severe hepatitis B than those of patients with chronic hepatitis respectively (chi(2) = 28.06, P = 0.000; chi(2) = 19.69, P = 0.000). The frequencies of the alleles and the genotypes of TNF-alpha-238G/A,-863C/A did not differ significantly between the chronic severe hepatitis B groups and chronic hepatitis B groups respectively (chi(2) = 0.61, P = 0.436; chi(2) = 0.001, P = 0.976), (chi(2) = 1.16, P = 0.552; chi(2) = 0.63, P = 0.486). the -308 GA, -857 TT genotypes were associated with chronic severe hepatitis B respectively, OR reaches 4.176 (95% CI 2.416 - 7.216) and 6.09 (95% CI 2.652 - 14.001). The serum level of TNF-alpha were higher in patients with chronic severe hepatitis B than the patients with chronic hepatitis B (44 pg/ml +/- 47 pg/ml vs 10 pg/ml +/- 4 pg/ml; t = 3.951, P = 0.000). CONCLUSION: The genetic polymorphisms at TNF-alpha sites are associated with the chronic severe hepatitis B and may play an important role on the progress of HBV infection as one of the host factors.