Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol-Liver-Intestine Axis Health.

Excessive alcohol intake will aggravate the health risk between the liver and intestine and affect the multi-directional information exchange of metabolites between host cells and microbial communities. Because of the side effects of clinical drugs, people tend to explore the intervention value of natural drugs on diseases. As a flavor substance, spices have been proven to have medicinal value, but they are still rare in treating hepatointestinal diseases caused by alcohol. This paper summarized the metabolic transformation of alcohol in the liver and intestine and summarized the potential value of various perfume active substances in improving liver and intestine diseases caused by alcohol. It is also found that bioactive substances in spices can exert antioxidant activity in the liver and intestine environment and reduce the oxidative stress caused by diseases. These substances can interfere with fatty acid synthesis, promote sugar and lipid metabolism, and reduce liver injury caused by steatosis. They can effectively regulate the balance of intestinal flora, promote the production of SCFAs, and restore the intestinal microenvironment.

AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway.

AKR1C3 is frequently overexpressed and it is a validated therapeutic target in various tumors including hepatocellular carcinoma (HCC). Our previous study showed that AKR1C3 facilitated HCC proliferation and metastasis by forming a positive feedback loop of AKR1C3-NF-κB-STAT3. Ferroptosis is a form of iron-dependent cell death driven by iron-dependent accumulation of lipid reactive oxygen species and plays an important role in tumor suppression. However, little is known about the role of AKR1C3 in ferroptosis susceptibility. In this study, we found that knockdown of AKR1C3 potently enhanced the sensitivity of HCC cells to ferroptosis inducers both in vitro and in vivo. Overexpression of AKR1C3 protected against ferroptosis in HCC cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC. AKR1C3 knockdown led to a decrease in YAP nuclear translocation, resulted in the inhibition of cystine transporter SLC7A11, and a subsequent increase in the intracellular levels of ferrous iron and ultimately ferroptosis. Moreover, we found that the combination of AKR1C3 and SLC7A11 was a strong predictor of poor prognosis in HCC. Collectively, these findings identify a novel role of AKR1C3 in ferroptosis, and highlighting a candidate therapeutic target to potentially improve the effect of ferroptosis-based antitumor therapy.

Novel lignans from Zanthoxylum nitidum and antiproliferation activity of sesaminone in osimertinib-resistant non-small cell lung cancer cells.

Seven previously undescribed tetrahydrofuran lignans with different configurations and unusual isopentenyl substitutions, nitidumlignans D-J (corresponding to compounds 1, 2, 4, 6, 7, 9 and 10), along with 14 known lignans, were isolated from Zanthoxylum nitidum. Notably, compound 4 is an uncommon naturally occurring furan-core lignan derived from tetrahydrofuran aromatization. The antiproliferation activity of the isolated compounds (1-21) was determined in various human cancer cell lines. The structure-activity study revealed that the steric positioning and chirality of the lignans exert important effects on their activity and selectivity. In particular, compound 3 (sesaminone) exhibited potent antiproliferative activity in cancer cells, including acquired osimertinib-resistant non-small-cell lung cancer (HCC827-osi) cells. Compound 3 also inhibited colony formation and induced the apoptotic death of HCC827-osi cells. The underlying molecular mechanisms revealed that 3 downregulated the activation of the c-Met/JAK1/STAT3 and PI3K/AKT/mTOR signaling pathways in the HCC827-osi cells. In addition, the combination of 3 and osimertinib exhibited synergistic effects on the antiproliferative activity against HCC827-osi cells. Overall, these findings inform the structure elucidation of novel lignans isolated from Z. nitidum, and sesaminone was identified as a potential compound for exerting antiproliferative effects on osimertinib-resistant lung cancer cells.

Molecular Oxygen Activation by Citric Acid Boosted Pyrite-Photo-Fenton Process for Degradation of PPCPs in Water.

Pyrite has been used in photo-Fenton reactions for the degradation of pollutants, but the application of photo-Fenton processes with extra H2O2 in real water/wastewater treatment has still been limited by the economic cost of H2O2 and artificial light sources. Herein, citric acid (CA) and simulated/natural sunlight are used to develop a pyrite-based photo-Fenton system (pyrite-CA-light) in situ generating H2O2 through the enhanced activation of molecular oxygen. The degradation of pharmaceuticals and personal care products (PPCPs), especially acetaminophen (APAP) as the main target pollutant, in the pyrite-CA-light system was investigated. The effects of influencing factors such as various organic acids, APAP concentration, pH, pyrite dosage, CA concentration and co-existing anions (HCO3-, Cl-, NO3-, SO42- and H2PO4-) were examined. At a pyrite dosage of 0.1 g L-1, CA concentration of 0.6 mM and an initial pH of 6.0, the degradation efficiency of APAP (30 µM) was 99.1% within 30 min under the irradiation of xenon lamp (70 W, λ ≥ 350 nm). Almost the same high efficiency of APAP degradation (93.9%) in the system was achieved under natural sunlight irradiation (ca. 650 W m-2). The scavenging experiments revealed that the dominant active species for degrading APAP was hydroxyl radical (HO•). Moreover, a quantitative structural-activity relationship (QSAR) model for pseudo-first-order rate constants (kobs) was established with a high significance (R2 = 0.932, p = 0.001) by using three descriptors: octanol-water partition coefficient (logKow), dissociation constant (pKa) and highest occupied molecular orbital (HOMO). This work provides an innovative strategy of the photo-Fenton process for the degradation of PPCPs using natural minerals and ordinary carboxylic acid under sunlight.

Four New Sesquiterpenoids from Zanthoxylum nitidum.

Zanthoxylum nitidum (Roxb.) DC., is one of Guangxi's characteristic national medicines, and is the classic Laoban medicine of Yao people "Ru Shan Hu" and Zhuang medicine "Liang Bei Zhen". It has been used as an anti-inflammatory, analgesic and haemostatic medicine for thousands of years. In this study, four new sesquiterpenoids (1-4), along with six previously described coumarins (5-10), were isolated from 95 % EtOH extract of Zanthoxylum nitidum. Comprehensive spectroscopic analyses (NMR and HR-ESI-MS) were used to elucidate the structures of these isolates. The absolute configurations of nitidumine A-D (1-4) were established by electronic circular dichroism (ECD). Their cytotoxicity of all the isolates against five cancer cell lines (T24, HeLa, MGC-803, A549, and HepG2) was evaluated by MTT experiment and found not to be cytotoxicity.

Film-Thickness Identification Method and Lubrication Characteristic Experiment of Full-Size Water-Lubricated Stern Bearing under Offset Load.

Water-lubricated stern bearing (WSB) is a vital part of the ship propulsion-shaft system, and it is of great significance to monitor and analyze its lubrication status through film thickness data to improve the equipment operational reliability. In this paper, a full-size, large length-to-diameter ratio WSB experiment is carried out, and multi-sectional journal displacement data are collected under offset load. Accordingly, a bearing film-thickness identification model is established, which can identify the dynamic film thickness data in the circumferential direction of bearing section by limited measurement points. On this basis, the film thickness distribution of the full bearing is obtained by combining finite element (FE) simulation and particle swarm optimization (PSO) algorithm. The effect of different speeds on the distributed lubrication characteristics of WSB under offset load was systematically analyzed based on film thickness data. Results show that the maximum identification error of the bearing film-thickness identification model is less than 7%. The bearing lubrication state changes dynamically as the speed increases, and the hydrodynamic lubrication effect in the middle of the bearing is enhanced. The area of each lubrication sub-region varies nonlinearly. Research results are instructive for further determine the service life of the shaft system.

Morusin Protected Ruminal Epithelial Cells against Lipopolysaccharide-Induced Inflammation through Inhibiting EGFR-AKT/NF-κB Signaling and Improving Barrier Functions.

Using phytogenic extracts for preventing or treating rumen epithelial inflammatory injury is a potential alternative to antibiotic use due to their residue-free characteristics. In this study, the efficacy of Morus root bark extract Morusin on ruminal epithelial cells (RECs) against pathogenic stimulus was investigated for the first time. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and quantitative real-time polymerase chain reaction (qPCR) results showed that the Morusin did not affect the cell viability of RECs and exerted anti-inflammatory effects in a concentration-dependent manner. Transcriptome analysis further revealed that the Morusin significantly downregulated the inflammatory-response-related cell signaling, while it upregulated the cell-proliferation-inhibition- and barrier-function-related processes in RECs upon lipopolysaccharide (LPS) stimulation. The epidermal growth factor receptor (EGFR) blocking and immunoblotting analysis further confirmed that the Morusin suppressed LPS-induced inflammation in RECs by downregulating the phosphorylation of protein kinase B (AKT) and nuclear factor-kappaB (NF-κB) p65 protein via inhibiting the EGFR signaling. These findings demonstrate the protective roles of Morusin in LPS-induced inflammation in RECs.

Oral health knowledge, attitudes, and practices and oral health-related quality of life among stroke inpatients: a cross-sectional study.

BACKGROUND: Stroke patients have poor oral hygiene, experience oral dysfunction due to disease factors, and have impaired oral health-related quality of life (OHRQoL). This study aimed to determine the oral health knowledge, attitudes, and practices of stroke inpatients, assess the OHRQoL of these patients, and identify their correlates. METHODS: In this cross-sectional study, 281 stroke inpatients aged between 22 and 88 years (57.94 ± 10.94) were conveniently selected from three hospitals in Guangzhou, China. OHRQoL was measured among these stroke patients using a Chinese version of the Oral Health Impact Profile-14 (OHIP-14). SPSS 26.0 was used for statistical analysis. Mean scores, standard deviations, and frequency distributions were obtained. The Mann-Whitney U test, Kruskal‒Wallis H test, Spearman's correlation, and multiple linear regression were used in the analysis. RESULTS: The mean score of the patients' OHRQoL was 8.37 ± 6.67, with the highest score in the pain or discomfort of the mouth dimension (3.11 ± 2.13) and pain being the most common negative effect (13.5%). In multiple linear regression analysis, significant differences were found between patients only in age (P = 0.008), toothache (P < 0.001), self-rated oral health (P < 0.001), time since last dentist visit (P = 0.037) and reason for not having visited a dentist in the past year (P < 0.001). CONCLUSION: The OHRQoL of patients hospitalised with stroke was moderate, and oral conditions still need to be improved. Increasing age, toothache, a longer time since the last dental visit and the reason for not visiting a dentist in the past year had a negative effect on OHRQoL, and better self-rated oral health had a positive effect. Therefore, in clinical work, greater attention should be given to elderly stroke patients, patients with poor oral status and poor oral health behaviours, timely assessment of patients' swallowing function, nutritional function, and self-care ability, and early and targeted oral health interventions and guidance.

Diagnosis and surgical treatment of primary isolated aggressive lumbar myeloid sarcoma: a rare case report and review of the literatures.

BACKGROUND: Myeloid sarcoma is a rare, extramedullary, solid tumor derived from immature myeloid cell precursors. It is most frequently accompanied by acute myelogenous leukemia, though infrequently found in non-acute myelogenous leukemia patients. The tumor may involve any part of the body, but the lumbar spine is seldom involved. The present case study aims to understand the diagnosis and surgical treatment of a rare primary isolated myeloid sarcoma of the lumbar spine causing aggressive spinal cord compression in a non-acute myelogenous leukemia patient. CASE PRESENTATION: A 29-year-old man complained of an aggressive radiating pain to the lower extremities and moderate dysuria with a Visual Analogue Scale score that gradually increased from 3 to 8. Lumbar enhanced magnetic resonance imaging and computed tomography revealed a lumbar canal lesion at lumbar spine L2 to L4 with spinal cord compression. A whole body bone scan with fused single photon emission computed tomography/computed tomography demonstrated abnormal 99mTc-methylene diphosphonate accumulation in the L3 lamina and spinous process. No evidence of infection or hematology disease was observed in laboratory tests. Due to rapid progression of the symptoms and lack of a clear diagnosis, decompression surgery was performed immediately. During the operation, an approximately 6.0 × 2.5 × 1.2 cm monolithic, fusiform, soft mass in the epidural space and associated lesion tissues were completely resected. The radiating pain was relieved immediately and the dysuria disappeared within 1 week. Intraoperative pathological frozen section analysis revealed a hematopoietic malignant tumor and postoperative immunohistochemistry examination confirmed the diagnosis of myeloid sarcoma. CONCLUSIONS: The primary isolated aggressive lumbar myeloid sarcoma is rarely seen, the specific symptoms and related medical history are unclear. Surgery and hematological treatment are effective for understanding and recognizing this rare tumor.

Calcium Sulfite Solids Activated by Iron for Enhancing As(III) Oxidation in Water.

Desulfurized gypsum (DG) as a soil modifier imparts it with bulk solid sulfite. The Fe(III)-sulfite process in the liquid phase has shown great potential for the rapid removal of As(III), but the performance and mechanism of this process using DG as a sulfite source in aqueous solution remains unclear. In this work, employing solid CaSO3 as a source of SO32-, we have studied the effects of different conditions (e.g., pH, Fe dosage, sulfite dosage) on As(III) oxidation in the Fe(III)-CaSO3 system. The results show that 72.1% of As(III) was removed from solution by centrifugal treatment for 60 min at near-neutral pH. Quenching experiments have indicated that oxidation efficiencies of As(III) are due at 67.5% to HO•, 17.5% to SO5•- and 15% to SO4•-. This finding may have promising implications in developing a new cost-effective technology for the treatment of arsenic-containing water using DG.

Electroreductive Olefin-Ketone Coupling.

A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI2 (which cannot accomplish the same reaction).

Metal-Free Electro-Activated Sulfite Process for As(III) Oxidation in Water Using Graphite Electrodes.

Transition-metal-activated sulfite [S(IV)] processes for water decontamination have recently received intense attention in the field of decontamination by advanced oxidation processes (AOPs). However, the drawback with respect to the secondary metal sludge contamination involved in various AOPs has been argued often. In this work, we developed a novel electro-sulfite (ES) process using stable and low-cost graphite electrodes to address that concern. Arsenite [As(III)] was used as the target compound for removal by the ES process because of its wide presence and high toxicity. Parameters, including cell voltage, S(IV) concentration, solution pH, and water matrix, and the mechanisms for reactions on anode and cathode were investigated in electrolytic cells containing one or two compartments, respectively. The results show that the ES process using 1 mM S(IV) and 2 V cell voltage oxidizes 5 µM As(III) at a rate of 0.127 min-1, which is 15-fold higher than mere electrolysis without S(IV) addition (0.008 min-1) at pH 7. Further studies using radical scavengers and electron spin resonance assays demonstrated that oxysulfur radicals (i.e., SO5•- and SO4•-) and HO• are responsible for As(III) oxidation in the ES process. However, HO2• produced via the oxygen reduction reaction in the EO process plays a major role in As(III) oxidation, which explains the lower reaction rate in the absence of S(IV). The effectiveness of the ES process was moreover evidenced by 60-82% As(III) oxidation in field water within 40 min. Overall, this work realizes the metal-free activation of S(IV) and significantly leverages the S(IV)-based water treatment technologies.

Clinical and radiological subsequent fractures after vertebral augmentation for treating osteoporotic vertebral compression fractures: a meta-analysis.

PURPOSE: This study aimed to identify all relevant randomized controlled trials (RCT) and prospective non-RCTs to further investigate whether percutaneous vertebral augmentation (PVA) was associated with clinical and radiological subsequent fractures on unoperated levels. METHODS: We systematically searched PubMed, EMBASE, Cochrane library, Google Scholar, web of science, and ClinicalTrial.gov from the establishment of the database to January 2020. All eligible studies comparing subsequent fractures after PVA with those after conservative treatment (CT) were incorporated. The pooled risk ratio (RR) with its 95% confidence intervals (95% CIs) was used. Heterogeneity, sensitivity, and publication bias analyses were performed. RESULTS: In all, 32 studies were included in the study: 82/512 patients (16.02%) and 58/433 patients (13.39%) had clinical subsequent fractures in the PVA group and CT group, respectively. No significant differences were observed between the two groups [RR = 1.22, 95% CI 0.70-2.12, P = 0.49]. Further, 175/837 patients (20.91%) in the PVA group and 160/828 patients (19.32%) in the CT group had radiological subsequent fractures. No significant difference was observed between groups [RR = 0.91, 95% CI 0.71-2.12, P = 1.16]. Further, no statistical difference was observed on subgroup analysis between RCTs and non-RCTs or PVP and PKP. CONCLUSION: Our systematic review revealed that subsequent fractures on unoperated levels were not associated with PVA, regardless of whether they were clinical or radiological subsequent fractures.

Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3 signaling pathway.

Long noncoding RNAs can serve as oncogenes or tumor suppressors in human cancer; however, their biological functions and underlying mechanism in hepatocarcinogenesis are largely unknown. Here, we report a novel tumor suppressor long noncoding RNA on chromosome 8p12 (termed TSLNC8) that is frequently deleted and down-regulated in hepatocellular carcinoma (HCC) tissues. The loss of TSLNC8 is highly associated with the malignant features of HCC and serves as a prognostic indicator for HCC patients. TSLNC8 significantly suppresses the proliferation and metastasis of HCC cells in vitro and in vivo. TSLNC8 exerts its tumor suppressive activity by competitively interacting with transketolase and signal transducer and activator of transcription 3 (STAT3) and modulating the STAT3-Tyr705 and STAT3-Ser727 phosphorylation levels and STAT3 transcriptional activity, thus resulting in inactivation of the interleukin-6-STAT3 signaling pathway in HCC cells. CONCLUSION: TSLNC8 is a promising prognostic predictor for patients with HCC, and the TSLNC8-transketolase-STAT3 axis is a potential therapeutic target for HCC treatment. (Hepatology 2018;67:171-187).

Comparison of clinical outcomes of expansive open-door laminoplasty with unilateral or bilateral fixation and fusion for treating cervical spondylotic myelopathy: a multi-center prospective study.

BACKGROUND: The present study evaluated the clinical outcomes and safety of expansive open-door laminoplasty, when securing with C4 - C6 lateral mass screw and fusion. METHODS: A total of 110 patients with cervical spondylotic myelopathy (CSM) were enrolled. There were 88 male and 22 female, with mean age at 60.55 ± 10.95 years. All of the patients underwent expansive open-door laminoplasty with unilateral or bilateral C4-6 lateral mass screws fixation and fusion. Clinical data, including age, gender, operation-related information, pre- and post-operation Japanese Orthopedic Association (JOA) scores, and cervical curvatures were collected. RESULTS: The mean follow-up time of the cohort was 13.61 ± 9.53 months. Among the 110 patients, 33 of them were allocated to Unilateral group, and 77 of them were in Bilateral group. The mean JOA score of the 110 patients before surgery was 10.07 ± 2.39, and the score was improved significantly to 12.85 ± 2.45 after surgery. There were no reported cases of neurological deterioration or symptom worsening. Patients in both the Unilateral group and Bilateral groups had significant improvement of JOA scores. Among all patients, the most frequently observed complications were axial symptoms (n = 7). The average preoperative cervical curvature among all patients was 15.17 ± 5.26, and the post-surgery curvature was 14.41 ± 4.29. Similar observations were found between Unilateral and Bilateral groups. CONCLUSION: The modified surgical approach provided satisfactory clinical outcome in patients with CSM. The unilateral and bilateral fixation appeared to provide similar outcomes, in terms of cervical curvature maintenance and improvement of clinical symptoms. However, the examination of the exact differences between the two fixation methods await further biomechanical studies.

The Evolution of the Minimally Invasive Approach and Conventional Median Sternotomy for Coronary Artery Fistula Correction.

BACKGROUND: Minimally invasive cardiac surgery has become a safe and cosmetic alternative to standard median sternotomy. This retrospective study reviews our results and experience with the minimally invasive approach for congenital coronary artery fistula correction, compared with conventional approach. METHODS: From February 2001 to June 2016, 110 patients with isolated coronary artery fistula (CAF) in our centre underwent correction through minimally invasive approach (MIA) (n=65) or standard median sternotomy (SMS) (n=45). Cardiopulmonary bypass (CPB) was used in 16 patients in the SMS group, and all the other patients underwent the procedure without CPB through a standard median sternotomy or minimally invasive approach. RESULTS: There was no in-hospital mortality and no patients reverted to a median sternotomy in the MIA group. Subxiphoid incision (32 cases) and parasternal incision (28 cases) were the most common approaches used for the procedure. The operative time was 67.82±14.4minutes in MIA group and 107.04±27.91minutes (p=0.0001) in the SMS group. The intubation time was 3.58±2.33hours in the MIA group and 6.1±3.26hours in the SMS group (p=0.0001); the intensive care unit (ICU) stay was 10.04±7.95hours in the MIA group and 19.74±7.81hours in the SMS group (p=0.0001). Three patients (two in MIA Group vs one in SMS Group, p=0.787) were identified with a trivial residual shunt during the procedure, which had disappeared by discharge. CONCLUSIONS: Minimally invasive approach can provide an excellent surgical exposure for CAF ligation in selective patients compared with SMS. It is a safe and cosmetic alternative to conventional treatment and minimised the length of stay.

NK3 homeobox 1 (NKX3.1) up-regulates forkhead box O1 expression in hepatocellular carcinoma and thereby suppresses tumor proliferation and invasion.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality in China, and the molecular mechanism of uncontrolled HCC progression remains to be explored. NK3 homeobox 1 (NKX3.1), an androgen-regulated prostate-specific transcription factor, suppresses tumors in prostate cancer, but its role in HCC is unknown, especially in hepatocellular carcinoma. In the present study, the differential expression analyses in HCC tissues and matched adjacent noncancerous liver tissues revealed that NKX3.1 is frequently down-regulated in human primary HCC tissues compared with matched adjacent noncancerous liver tissues. We also noted that NKX3.1 significantly inhibits proliferation and mobility of HCC cells both in vitro and in vivo Furthermore, NKX3.1 overexpression resulted in cell cycle arrest at the G1/S phase via direct binding to the promoter of forkhead box O1 (FOXO1) and up-regulation of expression. Of note, FOXO1 silencing in NKX3.1-overexpressing cells reversed the inhibitory effects of NKX3.1 on HCC cell proliferation and invasion. Consistently, both FOXO1 and NKX3.1 were down-regulated in human HCC tissues, and their expression was significantly and positively correlated with each other. These results suggest that NKX3.1 functions as a tumor suppressor in HCC cells through directly up-regulating FOXO1 expression.

Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.

Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated. In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC). Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects. Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells. TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase. Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT). TM inhibited migration and invasion of HCC cells by decreasing CD44 expression and altering its glycosylation. In addition, CD44s is involved in promoting EMT and is associated with a poor prognosis in HCC patients. Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration. The ability of TM to inhibit cell migration and invasion was enhanced or reversed in CD44s knockdown cells and cells overexpressing CD44s, respectively. The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells. Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-ß)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-ß-mediated loss of E-cadherin. In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.

Preoperative Alfa-Fetoprotein and Fibrinogen Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation Regardless of the Milan Criteria: Model Development with External Validation.

BACKGROUND/AIMS: Patient selection is critically important in improving the outcomes of liver transplantation for hepatocellular carcinoma. The aim of the current study was to identify biochemical measures that could affect patient prognosis after liver transplantation. METHODS: A total of 119 patients receiving liver transplantation for hepatocellular carcinoma were used to construct a model for predicting recurrence. The results were validated using an independent sample of 109 patients from independent hospitals. All subjects in both cohorts met the Hangzhou criteria. RESULTS: Analysis of the discovery cohort revealed an association of recurrence with preoperative fibrinogen and AFP levels. A mathematical model was developed for predicting probability of recurrence within 5 years: Y = logit(P) = -4.595 + 0.824 ×fibrinogen concentration (g/L) + 0.641 × AFP score (1 for AFP<=20ng/ml, 2 for 20 400ng/ml). At a cutoff score of -0.85, the area under the curve (AUC) was 0.819 in predicting recurrence (vs. 0.655 when using the Milan criteria). In the validation cohort, this model had reasonable performance in predicting 5-year overall survival (68.8% vs. 28.1% in using the -0.85 cutoff, p< 0.001) and disease-free survival (65.7% vs. 25.9%, p< 0.001). The sensitivity and specificity were 77.0% and 62.5%, respectively. The AUC of this newly developed model was similar to that with the Milan criteria (0.698 vs. 0.678). Surprisingly, the DFS in patients with score <= -0.85 under this model but not meeting the Milan criteria was similar to that in patients meeting the Milan criteria (53.8% vs. 60.0%, p=0.380). CONCLUSIONS: Preoperative AFP and fibrinogen are useful in predicting recurrence of hepatocellular carcinoma after liver transplantation.

Enzymatic synthesis of cefazolin using immobilized recombinant cephalosporin-acid synthetase as the biocatalyst.

A method for the synthesis of ß-lactam antibiotic cefazolin (CEZ) by enzymatic acylation of 7-amino-3-(5-methyl-l,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (TDA) using immobilized cephalosporin-acid synthetase (IECASA) from recombinant E. coli strain VKPM B-12316 has been developed. A stepwise pH gradient designed on the basis of investigations on the solubility of components was applied for synthesis. This helped in avoiding the precipitation of TDA in the reaction when its initial concentration was high (150-200 mM). Thus, under optimal conditions a high yield of CEZ (relative to TDA) of 92-95% was obtained. Where the final reaction mixture contained 65-85 mg/mL of CEZ, 4-5 mg/mL of unreacted TDA, and 40-60 mg/mL of the by-product, 1(H)-tetrazolylacetic acid (TzAA). Testing of optimized CEZ synthesis using IECASA in a batch reactor has proved sufficiently high operational stability of the biocatalyst, with its residual activity after the 25th cycle accounting for about 83 ± 2% of its starting value. The half-inactivation period of IECASA was estimated as 85 cycles of CEZ synthesis.