Glutamine synthetase-negative hepatocellular carcinoma has better prognosis and response to sorafenib treatment after hepatectomy.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS: GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.

Microwave ablation combined with lipiodol-microsphere mixed or conventional transarterial chemoembolization for the treatment of colorectal liver metastases: A retrospective study.

PURPOSE: To investigate the clinical outcomes of microwave ablation (MWA) combined with lipiodol-microsphere mixed transarterial chemoembolization (mTACE) or conventional TACE (cTACE) for patients with colorectal liver metastases (CRLM). MATERIALS AND METHODS: This retrospective study evaluated the medical records of patients with CRLM who underwent MWA combined with mTACE or cTACE from January 2018 to September 2021. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated during the follow-up. In addition, prognostic factors affecting survival were analyzed by univariate and multivariate methods. RESULTS: A total of 79 patients with CRLM were enrolled in the study (MWA-mTACE group, n = 38; MWA-cTACE group, n = 41). The patients who underwent MWA-mTACE had higher DCR (86.8% vs. 65.9%, P = 0.029) and better PFS (median, 8.1 vs. 5.5 months, P = 0.018) than those who underwent MWA-cTACE, but no significant difference was found in ORR (34.2% vs. 22.0%, P = 0.225) and OS (median, 15.7 vs. 13.0 months, P = 0.231). Further univariate and multivariate analyses indicated that MWA-mTACE was an independent positive factor for PFS, and abnormal carcinoembryonic antigen level was a hazard factor for OS. The postoperative laboratory tests and complications in patients who underwent MWA-mTACE were similar to those who underwent MWA-cTACE. CONCLUSION: Lipiodol-microsphere mixed TACE might be an effective and safe treatment to combine with microwave ablation for patients with colorectal liver metastases.

An Optimal Combination of Chemically Pure Compounds from Salvia miltiorrhiza for Inhibiting Cell Proliferation.

OBJECTIVE: Salvia miltiorrhiza (SM) is a traditional Chinese medicine used clinically to treat cardiovascular diseases, including atherosclerosis and myocardial infarction. Its therapeutic effect has been confirmed by many clinical and pharmacological studies. However, the optimal formulation of active ingredients in SM for treating cardiovascular diseases remains unclear. In this study, we determined the ratio of the optimal compatibility of SM ingredients DSS, Sal-A, Sal-B, and PAL (SABP)with a uniform and orthogonal optimized experimental design. In addition, we determined the anti-oxidation effect of SABP using Adventitial Fibroblasts (AFs). METHODS: By using a combination of uniform and orthogonal designs, we determined the optimal formulation of aqueous extract from SM. MTT assay was used to determine the inhibitory effects of these 4 components of SM on the AFs, which were isolated and cultured from the aorta. The reactive oxygen species (ROS) production in AFs was compared before and after SABP treatment. RESULTS: The optimal formulation of these 4 aqueous extracts from SM were 150 : 7 : 300 : 500, and their concentrations were S(1.5×10-4 mol/L), A(7×10-6 mol/L), B(3×10-4 mol/L), and P(5×10-4 mol/L). There were some synergies between these 4 components. Moreover, SABP decreased ROS production in AFs. CONCLUSION: These findings suggest that SABP inhibits the proliferation and oxidation stress in AFs. The present study provides new evidence that the efficacy and function generated from the optimal formulation of active ingredients in SM are better than lyophilized powder of SM.

Study on the Relationship between Emulsion Properties and Interfacial Rheology of Sugar Beet Pectin Modified by Different Enzymes.

The contribution of rheological properties and viscoelasticity of the interfacial adsorbed layer to the emulsification mechanism of enzymatic modified sugar beet pectin (SBP) was studied. The component content of each enzymatic modified pectin was lower than that of untreated SBP. Protein and ferulic acid decreased from 5.52% and 1.08% to 0.54% and 0.13%, respectively, resulting in a decrease in thermal stability, apparent viscosity, and molecular weight (Mw). The dynamic interfacial rheological properties showed that the interfacial pressure and modulus (E) decreased significantly with the decrease of functional groups (especially proteins), which also led to the bimodal distribution of particle size. These results indicated that the superior emulsification property of SBP is mainly determined by proteins, followed by ferulic acid, and the existence of other functional groups also promotes the emulsification property of SBP.

Effect of glycosylation with sugar beet pectin on the interfacial behaviour and emulsifying ability of coconut protein.

The aim of the present study was to investigate the effect of glycosylation with sugar beet pectin (SBP) on the interfacial behaviour and emulsifying ability of coconut protein (CP). The physical stabilities of the emulsions were predicted by transmission variation, droplet distribution and zeta potentials. The results showed that SBP-CP-stabilized emulsions showed better stability during centrifugation than those stabilized by CP because SBP-CP reduced the degree of variation in the CP transmission profile. The adsorption kinetics of all emulsifiers at the oil-water interface were determined to investigate the relationship between the interfacial behaviour and emulsion stability. The presence of SBP considerably reduced the adsorption rate of CP (0.698 mN/m/s1/2) and hampered the development of a highly viscoelastic network at the oil-water interface. The values of the dilatational elastic modulus (Ed = 19.477 mN/m) and dilatational viscous modulus (E = 19.719 mN/m) were approximately equal, indicating that the adsorption process was mainly dominated by elastic behaviour. Additionally, the SBP-CP interaction enhanced the dilatational property of the CP-absorbed layer.

Transcriptomic analysis of tea plant (Camellia sinensis) revealed the co-expression network of 4111 paralogous genes and biosynthesis of quality-related key metabolites under multiple stresses.

The tea plant is an essential economic plant in many countries. However, its growing season renders them vulnerable to stresses. To understand the transcriptomic influences of these stresses on tea plants, we sequenced and analyzed the transcriptomes under drought, high-temperature, and pest. Paralogs were identified by comparing 14 evolutionarily close genomes. The differentially expressed paralog (DEPs) genes were analyzed regarding single or multiple stresses, and 1075 of the 4111 DEPs were commonly found in all the stresses. The co-expression network of the DEPs and TFs indicated that genes of catechin biosynthesis were associated with most transcription factors specific to each stress. The genes playing a significant role in the late response to drought and pest stress mainly functioned in the early response to high-temperature. This study revealed the relationship between stress and regulation of QRM synthesis and the role of QRMs in response to these (a)biotic stresses.

Integrated transcriptomics and metabolomics analysis of catechins, caffeine and theanine biosynthesis in tea plant (Camellia sinensis) over the course of seasons.

BACKGROUND: Catechins, caffeine, and theanine as three important metabolites in the tea leaves play essential roles in the formation of specific taste and shows potential health benefits to humans. However, the knowledge on the dynamic changes of these metabolites content over seasons, as well as the candidate regulatory factors, remains largely undetermined. RESULTS: An integrated transcriptomic and metabolomic approach was used to analyze the dynamic changes of three mainly metabolites including catechins, caffeine, and theanine, and to explore the potential influencing factors associated with these dynamic changes over the course of seasons. We found that the catechins abundance was higher in Summer than that in Spring and Autumn, and the theanine abundance was significantly higher in Spring than that in Summer and Autumn, whereas caffeine exhibited no significant changes over three seasons. Transcriptomics analysis suggested that genes in photosynthesis pathway were significantly down-regulated which might in linkage to the formation of different phenotypes and metabolites content in the tea leaves of varied seasons. Fifty-six copies of nine genes in catechins biosynthesis, 30 copies of 10 genes in caffeine biosynthesis, and 12 copies of six genes in theanine biosynthesis were detected. The correlative analysis further presented that eight genes can be regulated by transcription factors, and highly correlated with the changes of metabolites abundance in tea-leaves. CONCLUSION: Sunshine intensity as a key factor can affect photosynthesis of tea plants, further affect the expression of major Transcription factors (TFs) and structural genes in, and finally resulted in the various amounts of catechins, caffeine and theaine in tea-leaves over three seasons. These findings provide new insights into abundance and influencing factors of metabolites of tea in different seasons, and further our understanding in the formation of flavor, nutrition and medicinal function.

Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer's disease.

Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disorder characterized by amyloid plaque accumulations, intracellular tangles and neuronal loss in certain brain regions. It has been shown that a disturbance of normal iron metabolism contributes to the pathophysiology of AD. However, the mechanism underlying abnormal iron load in the brain of AD patients is unclear. The frontal cortex, an important brain structure for executive function, is one of the regions affected by AD. We investigated the beneficial effects of active compounds of Epimedium, Astragaoside and Puerarin on iron metabolism in the frontal cortex of six-month-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mouse, a model of AD. Treatment with the active compounds reduced cognitive and memory deficits and damaged cell ultrastructure in APP/PS1 mice. These beneficial effects were associated with changes in expression levels of iron metabolism proteins in the frontal cortex, including divalent metal transporter with iron response element (DMT1-with IRE), divalent metal transporter without iron response element (DMT1-without IRE), transferrin (TF) and transferring receptor 1 (TfR1); three release proteins including the exporter ferroportin 1 (Fpn1), ceruloplasmin (CP) and hephaestin (HEPH), one increased storage iron protein ferritin and one iron regulating hormone hepcidin. These findings suggest that the active compounds improve cognition and memory in brain neurodegenerative disorders and these beneficial effects are associated with reduced impairment of iron metabolism. This study may provide a new strategy for developing novel drugs to treat AD.

[Clinical study on effect of Jianwei Yuyang Granule in treating patients with gastric ulcer].

OBJECTIVE: To observe the clinical effects of Jianwei Yuyang Granule (JYG) in treating patients with gastric ulcer and its influence on interleukin-1beta (IL-1beta) and basic fibroblast growth factor (bFGF) mRNA expression in gastric mucosa for exploring the therapeutic mechanism. METHODS: Fifty-six patients with confirmed gastric ulcer unader gastroscope and differentiated as Gan-stagnant Pi-deficient syndrome were randomly assigned to two groups, the treated group (26 cases) treated with JYG and the control group (30 cases) treated with famotidine and sucralfate, 4 weeks as one therapeutic course. The changes before and after treatment in clinical compliance, symptom integral, ulcer-healing rate, clinical effective rate, and HP-clearance rate were observed. And the gastric mucosa biopsy was fetched for morphological examination and IL-1beta and bFGF mRNA expression detection by RT-PCR as well. RESULTS: The clinical compliance rate in the treated group was 100 %, which was obviously better than that in the control group (86.7 %, P< 0.01); the improvement on symptom integral in the former was also better (P < 0.01); no statistical significance was shown in ulcer-healing rate, clinical effective rate and HP-clearance rate between the two groups. Morphological observation showed markedly decreased inflammatory cell infiltration, epithelial cell regeneration and rather regular glandular arrangement in both groups. The IL-1beta mRNA expression level decreased and that of bFGF increased in both groups after treatment significantly ( P < 0.01), but showed insignificant difference between the two groups. CONCLUSION: JYG, with its good clinical compliance, has favorable effects in relieving clinical symptoms, promoting endoscopic ulcer healing and HP clearance, decreasing the expression of IL-1beta mRNA and increasing the expression of bFGF, therefore, it could promote the recovering of gastric ulcer.