Circulating tumor DNA/circulating tumor cells and the applicability in different causes induced hepatocellular carcinoma

In 2015, liquid biopsy was rated one of the top 10 breakthrough technologies of the year by MIT Technology Review. Liquid biopsy is a type of in vitro diagnostic method involving a noninvasive blood test. It is also a breakthrough technology used to detect tumors and cancers and assist in therapeutic strategies. The most widely used markers are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Primary carcinoma of the liver is a malignancy of hepatocytes or intrahepatic biliary epithelial cells. The most common type of liver cancer is hepatocellular carcinoma (HCC), the causes of which mainly include infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), alcohol abuse, aflatoxicosis, and nonalcoholic fatty liver disease/ nonalcoholic steatohepatitis. As there are few typical clinical characteristics during the early stage of the disease, early diagnosis of HCC is very challenging. However, CTCs and ctDNA carry tumor-specific information. Therefore, the detection and analysis of CTCs and ctDNA can provide evidence for the early diagnosis of HCC and guide treatment. Furthermore, several studies have indicated that different inducers of HCC cause different DNA mutations, and accordingly, detection of specific mutations in ctDNA will facilitate the determination of the HCC type and help physicians provide distinctive therapies.     

Altered gut microbiota and mucosal immunity in patients with schizophrenia

Evidence shows that gut microbiota may play important roles in schizophrenia pathogenesis via the “gut-brain” axis, but the mechanisms remain unclear. Here, eighty-four patients with schizophrenia and 84 sex- and age-matched healthy controls were enrolled. Shotgun metagenomic sequencing and 16S rRNA sequencing were performed, and the gut microbiota-associated epitopes (MEs) were predicted, which, together with IgA content, were used to determine the gut microbiota composition associated with gut immune status. Patients with schizophrenia had significantly reduced gut microbiota richnesses compared with those of the healthy controls, and the gut microbiota compositions clearly distinguished the patients with schizophrenia from the healthy controls. Based on two-stage metagenomic-wide association studies, nineteen gut microbiota taxonomies were associated with schizophrenia, and the microbial dysbiosis (MD) index was calculated based on the abundance of differential taxonomies. We found that MD index was positively correlated with MEs diversity and gut IgA levels, and negatively correlated with gut microbiota richness. Glutamate synthase (GOGAT) was more active in the guts of patients with schizophrenia than in those of healthy controls, and high GOGAT activity was associated with altered gut microbiota taxonomies associated with gut IgA levels. Our results may imply a role of the microbiome in the etiology of schizophrenia and contribute to the development of microbiome targeted interventions for schizophrenia.     

Sciadopitysin suppresses RANKL-mediated osteoclastogenesis and prevents bone loss in LPS-treated mice

Previous studies reported that sciadopitysin (Sc), a type of biflavonoids, protects reactive oxygen species (ROS)-mediated osteoblast dysfunction, but its role in osteoclastogenesis remains unclear. In this study, we observed that Sc dose-dependently suppressed RANKL-induced osteoclastogenesis and bone resorption. Our results indicated that Sc treatment strongly reduced RANKL-induced osteoclast-specific genes expression, including cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP) and MMP-9. Furthermore, Sc apparently attenuated RANKL-increased expressions of c-Fos and NFATc1. Meanwhile, Sc also strikingly inhibited the activation of NF-κB without altering the phosphorylation of MAPKs (p38, JNK and ERK1/2). Finally, our study demonstrated that Sc administration could reverse the bone loss in LPS-induced mice model. This study suggests that Sc inhibits RANKL-induced osteoclastogenesis and bone loss by inhibiting NF-κB activation and reducing the expression of c-Fos and NFATc1. Therefore, Sc might be benefit for RANKL-mediated osteolytic bone diseases.     

The Prognostic Significance of Elevated Levels of Serum Ferritin Before Chemotherapy in Patients With Non-Hodgkin Lymphoma

BackgroundElevated levels of serum ferritin have been documented to be an adverse prognostic factor in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation. The purpose of this study was to estimate the correlation between elevated levels of serum ferritin and survival outcomes in patients with non-Hodgkin lymphoma (NHL).Patients and MethodsA total of 267 patients who were newly diagnosed with NHL and who received chemotherapy between September 1999 and April 2012 were retrospectively analyzed.ResultsIn multivariate analysis, other chemotherapy regimens excluding CHOP-like chemotherapy regimens (cyclophosphamide, adriamycin, vincristine, prednisolone) and RCHOP (rituximab plus CHOP), a high level of β2-microglobulin, a high-intermediate/high risk according to the international prognostic index (IPI), and elevated levels of serum ferritin were all significant independent prognostic factors for 5-year progression-free survival rates. RCHOP and other chemotherapy regimens, a high level of β2-microglobulin, a high-intermediate/high IPI risk, and high levels of serum ferritin were significant independent prognostic factors for 5-year overall survival rates.ConclusionElevated levels of serum ferritin of 500 ng/mL or more as well as the use of chemotherapy regimens besides CHOP-like or RCHOP, a high-intermediate/high risk IPI, and a high level of beta2-microglobulin in NHL may be an important marker for predicting poor survival outcomes.     

Inhibition of endocan attenuates monocrotaline-induced connective tissue disease related pulmonary arterial hypertension

Connective tissue disease related pulmonary arterial hypertension (CTD-PAH) is characterized by vascular remodeling, endothelial dysfunction and inflammation. Endocan is a novel endothelial dysfunction marker. The aim of the present study was to investigate the role of endocan in CTD-PAH. Monocrotaline (MCT)-induced PAH rats were used as the CTD-PAH model. Short hairpin RNA packed in a lentiviral vector used to inhibit endocan expression was intratracheally instilled in rats prior to the MCT injection. Endocan was found to be increased in the serum and lung of MCT-induced PAH rats. Short hairpin RNA mediated knockdown of endocan significantly decreased right ventricular systolic pressure, attenuated pulmonary remodeling and inflammatory responses in the lung. In the in vitro study, tumor necrosis factor-α (TNF-α) exposure caused increased endocan expression in the primary cultured rat pulmonary microvascular endothelial cells (RPMECs). Endocan knockdown inhibited the permeability increase and adhesion molecules secretion in RPMECs induced by TNF-α. In addition, TNF-α induced MAPK activation was blocked when endocan gene was knocked down. These data demonstrate that endocan may play an important role in the development of CTD-PAH. This study provides novel evidence to better understand the pathogenesis of CTD-PAH, which may be beneficial for the treatment of this disease.     

Low dose naltrexone (LDN) enhances maturation of bone marrow dendritic cells (BMDCs)

It has been demonstrated previously that immune cell activation and proliferation were sensitive to the effects of naltrexone, a non-peptidic δ-opioid receptor selective antagonist and opioid receptors on BMDCs have been detected [1]. However, there is little prior data published on naltrexone and DCs. Therefore, we hypothesized that LDN could exert modulating effect on BMDCs. In present study, we studied influence of LDN on both phenotypic and functional maturation of BMDCs. Changes of BMDC post-treatment with LDN were evaluated using conventional light microscope and transmission electron microscopy (TEM); flow cytometry(FCM); cytochemistry; acid phosphatase activity(ACP) test; FITC-dextran bio-assay; mixed lymphocytes and enzyme-linked immunosorbent assay (ELISA). We have found that LDN enhances maturation of BMDCs as evidenced by 1) up-regulating the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down-regulating the rates of pinocytosis and phagocytosis accompanied by the results of decreased ACP, and FITC-dextran bio-assay; 3) mounting potential of BMDCs to drive T cell; and 4) inducing secretion of higher levels of IL-12 and TNF-α. It is therefore concluded that LDN can efficiently promote the maturation of BMDCs via precise modulation inside and outside BMDCs. Our study has provided meaningful mode of action on the role of LDN in immunoregulation, and rationale on future application of LDN for enhancing host immunity in cancer therapy and potent use in the design of DC-based vaccines for a number of diseases.     

Anesthetic gases and occupationally exposed workers

The aim of this study is to estimate whether the occupational exposure to low dose anesthetic gases could cause alterations of blood parameters in health care workers. 119 exposed subjects and 184 not exposed controls were included in the study. Each worker underwent the complete blood count test (CBC), proteinaemia, leukocyte count, serum lipids, liver and kidney blood markers.The liver blood markers show statistically significant differences in health care workers compared with controls (p < 0.05), a statistically significant decrease in neutrophils and an increase of lymphocytes in health care workers compared with controls (p < 0.05). The prevalence of values outside the range for GPT, GGT, total bilirubin, lymphocytes and neutrophils was statistically significant in health care workers compared with controls (p < 0.05). The results suggest that occupational exposure to low dose anesthetic gases could influence some haematochemical hepatic and hematopoietic parameters in exposed health care workers.     

Nutrition as Therapy in Liver Disease

PurposeThe importance of nutrition is often underrecognized in the routine clinical care of patients with chronic liver disease. Nutrition therapy plays a significant role in the management of alcohol-related liver disease and nonalcoholic fatty liver disease. In patients with cirrhosis from any etiology, malnutrition and sarcopenia are directly related to mortality, and nutritional interventions play an important role in the management of these patients. This review explores the role of nutritional intervention as adjuvant therapy across all chronic liver disease.MethodsA narrative, qualitative systematic review was performed via searches of PubMed for nutritional aspects in the care of chronic liver disease.FindingsNutritional therapy plays a critical role in the management of chronic liver disease. In nonalcoholic fatty liver disease, specific macronutrient management can lead to weight loss and improved outcomes in these patients. In patients with alcohol-related liver disease, chronic cholestatic liver disease, and decompensated cirrhosis, caloric and protein intake plays a vital role improving outcomes in these patients. Micronutrient deficencies are also common in these patients and require supplementation to prevent other complications of malnutrition. Assessment and management of nutrition should accompany the typical care plan of patients with chronic liver disease.ImplicationsThis review of nutritional therapy in chronic liver disease highlights the current evidence-based and societal recommendations of macronutrient and micronutrient management across the spectrum of all chronic liver disease.