Molecular characterization of vascular endothelial growth factor b from spotted sea bass (Lateolabrax maculatus) and its potential roles in decreasing lipid deposition.

Vascular endothelial growth factor B (VEGFB), a member of the VEGF family, exhibits limited angiogenic activity in mammals but plays an unexpected role in targeting lipids to peripheral tissues. However, its role in lipid metabolism in fish is unknown. In this study, the vegfb gene was cloned and characterized from spotted sea bass (Lateolabrax maculatus). It encodes 254 amino acids and possesses the typical characteristics of the Vegfb family, demonstrating high homology with those from other vertebrate species. The vegfb gene exhibits the highest expression levels in the liver, followed by the gills, intestine, and adipose tissues in spotted sea bass. In vivo, high-lipid diets decreased vegfb expression and increased lipid deposition in liver of fish. In vitro, palmitic acid + oleic acid treatment or vegfb knockdown significantly increased TG and TC contents, promoting lipid droplet deposition in hepatocytes. Vegfb overexpression has the opposite effects, inhibiting lipid deposition and downregulating fatty acid transport and adipogenesis genes. In contrast, the vegfb knockdown significantly upregulated the expression levels of c/ebpα, plin2, and dgat1 (P < 0.05). These results demonstrate that Vegfb may play an important role in reducing lipid deposition by regulating fatty acid transport and adipogenesis in the hepatocytes of spotted sea bass.

Galectin-1 promotes gastric cancer peritoneal metastasis through peritoneal fibrosis.

BACKGROUND: Peritoneal metastasis is one of the main causes of death in patients with gastric cancer (GC). Galectin-1 regulates various undesirable biological behaviors in GC and may be key in GC peritoneal metastasis. METHODS: In this study, we elucidated the regulatory role of galectin-1 in GC cell peritoneal metastasis. GC and peritoneal tissues underwent hematoxylin-eosin (HE), immunohistochemical (IHC), and Masson trichrome staining to analyze the difference in galectin-1 expression and peritoneal collagen deposition in different GC clinical stages. The regulatory role of galectin-1 in GC cell adhesion to mesenchymal cells and in collagen expression was determined using HMrSV5 human peritoneal mesothelial cells (HPMCs). Collagen and corresponding mRNA expression were detected with western blotting and reverse transcription PCR, respectively. The promoting effect of galectin-1 on GC peritoneal metastasis was verified in vivo. Collagen deposition and collagen I, collagen III, and fibronectin 1 (FN1) expression in the peritoneum of the animal models were detected by Masson trichrome and IHC staining. RESULTS: Galectin-1 and collagen deposition in the peritoneal tissues was correlated with GC clinical staging and were positively correlated. Galectin-1 enhanced the ability of GC cells to adhere to the HMrSV5 cells by promoting collagen I, collagen III, and FN1 expression. The in vivo experiments confirmed that galectin-1 promoted GC peritoneal metastasis by promoting peritoneal collagen deposition. CONCLUSION: Galectin-1-induced peritoneal fibrosis may create a favorable environment for GC cell peritoneal metastasis.

Galectin-1-mediated high NCAPG expression correlates with poor prognosis in gastric cancer.

Galectin-1 (Gal1) and non-SMC condensin I complex, subunit G (NCAPG) are associated with metastasis in several malignant tumors. However, their precise roles in gastric cancer (GC) remain uncertain. This study explored the clinical significance and relationship of Gal1 and NCAPG in GC. Gal1 and NCAPG expressions were significantly up-regulated in GC compared to adjacent non-cancerous tissues by immunohistochemistry (IHC) and Western blotting. Besides, methods including stable transfection, quantitative real-time reverse transcription PCR, Western blotting, Matrigel invasion and wound-healing assays in vitro, were also conducted. IHC scores for Gal1 and NCAPG had a positive correlation in GC tissues. High Gal1 or NCAPG expression significantly correlated with poor prognosis in GC, and Gal1 combined with NCAPG had a synergetic effect on the prediction of GC prognosis. Gal1 overexpression in vitro enhanced NCAPG expression, cell migration, and invasion in SGC-7901 and HGC-27 cells. Simultaneous Gal1 overexpression and NCAPG knockdown in GC cells partly rescued the migrative and invasive abilities. Thus, Gal1 promoted GC invasion through increased NCAPG expression. The present study demonstrated the prognostic significance of the combination of Gal1 and NCAPG in GC for the first time.

Recent Research Progress into Zinc Ion Battery Solid-Electrolyte Interfaces.

Aqueous zinc ion batteries (ZIBs) are prospective next-generation energy storage device candidates owing to resource abundance, affordability, eco-friendliness, and safety. The solid-electrolyte interface (SEI) produced in a ZIB by electrolyte/electrode interactions significantly impacts battery performance. The SEI is known to promote dendrite growth, determine the electrochemical stability window, passivate zinc-metal-anodic corrosion, and mutate the electrolyte. Accordingly, the SEI is closely related to the overall property of a ZIB device. This review provides an overview of the impact of SEIs on ZIB performance recently and provides an SEI design strategy based on the formation mechanism, type, and characteristics of the SEI. Finally, future investigational directions for SEIs in ZIBs are expected to lead to a deep understanding of the SEI, enhance ZIB performance, and facilitate their extensive implementation.

Improved strategies for ammonium vanadate-based zinc ion batteries.

Aqueous zinc ion batteries (ZIBs) are becoming increasingly popular as a new form of resource for electrochemical energy storage due to their high safety, affordability, availability of natural zinc resources, and high gravimetric energy density. However, the development of high-performance ZIB cathode materials remains a great challenge because current ZIB cathode materials tend to have low conductivity and relatively complex energy storage mechanisms. Compared with other cathode materials, ammonium vanadate-based materials have been extensively investigated as cathode materials for ZIBs due to their plentiful availability and high potential capacity. In this review, we highlight the mechanisms and challenges of ammonium vanadate-based materials and summarize the progress in improved strategies including the design of different morphologies, doping with different impurities, the introduction of different intercalators, and combination with other materials for high-performance ZIBs. Finally, the paper also provides an outlook on the future challenges and development prospects of ammonium vanadate-based cathode materials in ZIBs.

Improved Strategies for Separators in Zinc-Ion Batteries.

The demand for energy storage is growing, and the disadvantages of lithium-ion batteries are being explored to overcome them. Accordingly, aqueous zinc-ion batteries (ZIBs) are developing very rapidly, owing to their high safety, environmental friendliness, high abundance of resources, and high cost performance. Over the last decade, ZIBs have made remarkable progress through extensive efforts in the field of electrode materials and through fundamental understanding of non-electrode components, such as solid-electrolyte interphase, electrolytes, separators, binders, and current collectors. In particular, the breakthrough in using separators on non-electrode elements should not be overlooked as such separators have proven key to conferring ZIBs with high energy and power density. In this Review, recent progress in the development of separators in ZIBs is comprehensively summarized based on their functions and roles in ZIBs, including the modification of conventional separators and the development of novel separators. Finally, the prospects and future challenges of separators are also discussed to facilitate ZIBs development.

Efficacy of DC-CIK Immunotherapy Combined with Chemotherapy on Locally Advanced Gastric Cancer.

The aim of the study is to explore the efficacy and safety of dendritic cell-cytokine-induced killer cell (DC-CIK) immunotherapy combined with chemotherapy in the treatment of locally advanced gastric cancer (LAGC). Among 106 patients with LAGC, 53 received the treatment of oxaliplatin-5-fluorouracil chemotherapy (control group), while the remaining 53 received DC-CIK immunotherapy combined with chemotherapy (DC-CIK group). The short-term efficacy and the changes in immune function indexes (cluster of differentiation (CD)3+, CD4+, CD8+, CD4+/CD8+, and natural killer (NK) cells) were analyzed. The overall response rate (ORR) was 47.2% (25/53) and 41.5% (22/53), and the disease control rate (DCR) was 69.8% (37/53) and 50.9% (27/53), respectively, in the DC-CIK group and the control group. It could be seen that the ORR had no statistically significant difference between the two groups, while the DCR in the DC-CIK group was significantly better than that in the control group. After treatment, the proportions of CD3+ T lymphocytes, CD4+ T lymphocytes, CD4+/CD8+ cells, and NK cells obviously rose, while the proportion of CD8+ T lymphocytes obviously declined in the DC-CIK group compared with those in the control group. After treatment, the scores in the function module of the QLQ-C30 scale were greatly higher in the DC-CIK group than those in the control group, while the scores of loss of appetite, constipation, dyspnea, fatigue, pain, and sleep disorders in the symptom module were significantly lower in the DC-CIK group than those in the control group. The median survival time was 23.4 months and 18.6 months, respectively, in the DC-CIK group and the control group. The results of the log-rank test showed that the OS in the DC-CIK group was remarkably superior to that in the control group. DC-CIK immunotherapy combined with chemotherapy can improve the immune cell function, ameliorate the quality of life, and prolong the survival time of LAGC patients, with fewer adverse reactions.

Steroid Receptor Coactivator-1 (SRC-1) Promoted Cell Metastasis of Gastric Cancer via VEGFC Activator by NF-κB.

The regulatory mechanism and function of steroid receptor coactivator-1 (SRC-1) was determined in vitro and the role played in gastric cancer was investigated. The study collected 64 patients with gastric cancer tissue and paracancerous tissue to investigate the clinical patterns of SRC-1 expression in gastric cancer. Quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, and immunofluorescence staining were used in this study. In patients with gastric cancer, SRC-1 serum expression levels were up-regulated. Over-expression of SRC-1 promoted cell growth and cell metastasis in vitro model of gastric cancer. However, down-regulation of SRC-1 reduced cell growth and cell metastasis in vitro model of gastric cancer. SRC-1 over-expression induced vascular endothelial growth factor C (VEGFC) protein expressions in vitro model by activation of nuclear factor-kappa B (NF-kB) expression. The inhibition of NF-κB reduced the pro-cancer effects of SRC-1 on cell growth and cell metastasis in vitro model of gastric cancer through inhibition of VEGFC expression. These results suggest that SRC-1 promoted cell metastasis of gastric cancer via VEGFC activator by NF-κB. These novel findings may shed further light on the pathogenesis of gastric cancer and on potential precursor markers.

Duodenal-Distal Ileal Fistula After Laparoscopic Radical Right Hemicolectomy: A Case Report.

Right hemicolectomy for colon cancer may be complicated by leaks, stenoses, or fistulas. These complications usually occur at the ileocolic anastomosis and can be managed endoscopically. However, fistulas that are large cannot be managed by endoscopy and require surgical intervention. After laparoscopic radical right hemicolectomy, duodenal fistulae is relatively rare. Among duodenal fistulae, internal duodenocolic fistulae is relatively common, but duodeno-ileum fistulae is extremely rare. Here, we report a case of duodeno-distal ileum fistula after right hemicolectomy with short bowel syndrome, that was surgically treated. After surgical treatment, the symptoms of short bowel syndrome disappeared, weight gain was obvious, and the clinical effect was satisfactory.

KLF5 activates lncRNA DANCR and inhibits cancer cell autophagy accelerating gastric cancer progression.

Cancer cell autophagy has been associated with the progression of gastric cancer (GC), but involvement of long noncoding RNAs (lncRNAs) remains unclear. Initial bioinformatics analysis has identified abnormally highly expressed KLF5 in GC, as well as the predicted regulatory mechanism associating with lncRNA DANCR, miR-194, and AKT2. The expression of KLF5, DANCR, and AKT2 in GC tissue was upregulated, and the expression of miR-194 was downregulated. We knocked KLF5 down and manipulated the expression of DANCR, miR-194, and AKT2 to characterize their roles in GC cell viability, autophagy, and apoptosis. The mechanistic investigations revealed that KLF5 activated the transcription of DANCR in the promoter region and elevated its expression. DANCR acted as a miR-194 sponge to repress its expression in GC. MiR-194 targeted and inhibited AKT2 expression. Silencing KLF5 augmented GC cell autophagy, apoptosis and impeded its viability through the DANCR/miR-194/AKT2 axis. The tumor-inhibiting properties of KLF5 knockdown were substantiated in vivo. Together, our study uncovered the oncogenic role of KLF5-dependent lncRNA DANCR transcription in GC in vivo and in vitro, which implicates the miR-194/AKT2 axis in tumor growth regulation, and it may be a potential therapeutic target for human GC.

Upregulation of circRNA_100395 sponges miR-142-3p to inhibit gastric cancer progression by targeting the PI3K/AKT axis.

Gastric cancer (GC) has a high morbidity and mortality, hence it is very important to elucidate the molecular pathogenesis mechanism of GC progression in order to find new treatment strategies. The present study aimed to explore the biological function of circular RNA_100395 (circRNA_100395) in GC. The expression level of circRNA_100395 in GC tissues, as well as normal epithelial cells and various gastric cancer cell lines, was detected using reverse transcription-quantitative PCR. Cell Counting Kit-8, EdU assay, flow cytometry and Transwell assays were performed to investigate cell proliferation, apoptosis, migration and invasion, respectively. A dual-luciferase reporter assay was performed to detect the correlation between circRNA_100395 and micro (mi)RNA-142-3p. Western blotting was performed to elucidate the potential regulatory mechanism. circRNA_100395 expression was found to be increased in GC tissues and cell lines. However, miR-142-3p expression was significantly reduced. Besides, low expression levels of circRNA_100395 were associated with poor tumor differentiation, advanced Tumor-Node-Metastasis stage, lymph node metastasis and shorter overall survival time. Moreover, overexpression of circRNA_100395 suppressed cell proliferation, increased the apoptosis rate and suppressed cell invasion and migration by inhibiting the PI3K/AKT signaling pathway. These findings also showed that miRNA-142-3p rescued the antitumor effects induced by circRNA_100395-overexpression. cirRNA_100395-overexpression had antitumor effects via regulating the miR-142-3p signaling pathway, which might be a promising treatment target for GC.

Galectin-1 promotes vasculogenic mimicry in gastric adenocarcinoma via the Hedgehog/GLI signaling pathway.

BACKGROUND: Galectin-1 (GAL-1), which is encoded by LGALS1, promotes vasculogenic mimicry (VM) in gastric cancer (GC) tissue. However, the underlying mechanism remains unclear. METHODS: Immunohistochemical (IHC) and CD34-periodic acid-Schiff (PAS) double staining were used to investigate Glioma-associated oncogene-1(GLI1) expression and VM in paraffin-embedded sections from 127 patients with GC of all tumor stages. LGALS1 or GLI1 were stably transduced into MGC-803 cells and AGS cells, and western blotting, IHC, CD34-PAS double staining and three-dimensional culture in vitro, and tumorigenicity in vivo were used to explore the mechanisms of GAL-1/ GLI1 promotion of VM formation in GC tissues. RESULTS: A significant association between GAL-1 and GLI1 expression was identified by IHC staining, as well as a significant association between GLI1 expression and VM formation. Furthermore, overexpression of LGALS1 enhanced expression of GLI1 in MGC-803 and AGS cells. GLI1 promoted VM formation both in vitro and in vivo. The effects of GLI1 on VM formation were independent of LGALS1. Importantly, the expression of VM-related molecules, such as MMP2, MMP14 and laminin5γ2, was also affected upon GLI1 overexpression or silencing in GC cell lines. CONCLUSION: GAL-1 promotes VM in GC through the Hh/GLI pathway, which has potential as a novel therapeutic target for treatment of VM in GC.

[Application of double-pouch anastomosis in laparoscopic radical resection of rectal cancer assisted by small incision].

OBJECTIVE: To explore the feasibility, safety and the economical efficiency of double-pouch anastomosis in laparoscopic radical rectal cancer assisted by small incisions. METHODS: Clinical data of 224 patients undergoing gastrointestinal surgery at Taizhou People's Hospital of Jiangsu Province from January 2011 to December 2017 were retrospectively analyzed. Indusion criteria: patients were diagnosed as primary rectal adenocarcinoma by preoperative enteroscopy pathology, the distance of the tumor to anal margin was from 4 to 15 cm, and patients were treated with laparoscopic total mesorectal excision(TME) through small incision. Patients were divided into two groups according to different anastomosis method, double-pouch group(108 cases) and single-pouch group (116 cases). The surgical indexes, tumor safety indexes, short-term efficacy and economic indexes were compared between the two groups. RESULTS: There was no significant difference between two groups in baseline data, operative time, blood loss, number of lymph nodes dissection, average length of proximal and distal bowel, or incidence of urination and sexual dysfunction (all P>0.05). Compared with the single-pouch group, the double-pouch group presented lower anastomotic secondary bleeding rate [0.9%(1/108) vs. 6.0% (7/116), χ²=4.238, P=0.040], lower incidence of anastomotic leakage[1.9%(2/108) vs. 7.8%(9/116), χ²=4.179, P=0.041], lower incidence of anastomotic stricture [1.9% (2/108) vs. 8.6% (10/116), χ²=5.054, P=0.025], shorter hospital stay [(13.4±3.9) days vs. (15.9±9.8) days, t=2.524, P=0.013] and less average hospitalization costs [(34 000±7 000) yuan vs. (46 000±23 000) yuan, t=5.047,P<0.001]. There was no significant difference in local recurrence, distant metastasis or overall survival between the two groups during mean follow-up of 33 months (all P>0.05). CONCLUSION: Laparoscopic TME assisted by small incision with double-pouch anastomosis is a safe, feasible and economical method.

[Clinical significance of No.12 lymph node dissection for advanced gastric cancer].

OBJECTIVE: To evaluate the clinical significance of No.12 lymph node dissection for advanced gastric cancer with D2 lymphadenectomy. METHODS: Clinicopathologic data and No.12 lymph node dissection of 256 advanced gastric cancer patients undergoing radical operation in our department between January 2005 and December 2010 were retrospectively summarized and the influence factors of metastasis in No.12 lymph nodes were analyzed. RESULTS: Of 256 patients, 179 were male and 77 were female with the average age of 59.2 years. Tumor located in the upper of stomach in 24 cases, middle of stomach in 41 cases, lower of stomach in 174 cases, multi-focus or diffuse distribution of stomach in 17 cases. Tumor diameter was <3 cm in 39 cases, 3 to 5 cm in 100 cases, >5 cm in 117 cases. Serum carcinoembryonic antigen (CEA) level increased in 61 cases, serum carbohydrate antigens (CA)72-4 increased in 56 cases and CA19-9 increased in 61 cases. The number of No.12 lymph nodes resected from all the patients was 1 152, and the average number was 4.5±1.9. The metastasis rate of No.12 lymph nodes was 9.4%(24/256) after hematoxylin eosin staining (positive group). All the patients received effective follow-up to December 2015, and the average follow-up time was 101.2 months. The median survival time of positive No.12 group (24 cases) was 29.8 months and of negative No.12 group (232 cases) was 78.2 months, whose difference was statistically significant (χ2=21.715, P=0.000). Univariate analysis found that No.12 lymph node metastasis was not associated with age, gender, tumor differentiation (all P>0.05), but was associated with tumor location, tumor diameter, invasive depth (all P<0.05), and was closely associated with Borrmann type, outside metastatic lymph nodes of No.12 and high levels of serum CEA, CA72-4 and CA19-9 (all P=0.000). Multivariate regression analysis found that tumor location (RR=2.452, 95%CI:1.537 to 3.267, P=0.000), Borrmann type (RR=1.864, 95%CI:1.121 to 3.099, P=0.016) and number of outside metastatic lymph nodes of No.12 (RR=2.979, 95%CI: 2.463 to 3.603, P=0.000) were the independent risk factors of the No.12 metastasis (P<0.05). CONCLUSIONS: Metastasis in No.12 lymph nodes indicates poorer prognosis. The No.12 lymph nodes of advanced gastric cancer patients with curative resection, especially those with the tumor located in the lower part, Borrmann type IIII(, outside metastatic lymph nodes of No.12, should be regularly cleaned.

Fluorimetric urease inhibition assay on a multilayer microfluidic chip with immunoaffinity immobilized enzyme reactors.

We fabricated a three-layer polydimethylsiloxane (PDMS)-based microfluidic chip for realizing urease inhibition assay with sensitive fluorescence detection. Procedures such as sample prehandling, enzyme reaction, reagent mixing, fluorescence derivatization, and detection can be readily carried out. Urease reactors were prepared by adsorption of rabbit immunoglobulin G (IgG) and immunoreaction with urease-conjugated goat anti-rabbit IgG. Acetohydroxamic acid (AHA) as a competitive inhibitor of urease was tested on the chip. Microfluidically generated gradient concentrations of AHA with substrate (urea) were loaded into urease reactors. After incubation, the produced ammonia was transported out of reactors and then reacted with o-phthalaldehyde (OPA) to generate fluorescent products. Urease inhibition was indicated by a decrease in fluorescence signal detected by microplate reader. The IC50 value of AHA was determined and showed good agreement with that obtained in microplate. The presented device combines several steps of the analytical process with advantages of low reagent consumption, reduced analysis time, and ease of manipulation. This microfluidic approach can be extended to the screening of inhibitory compounds in drug discovery.

ZNRF3 acts as a tumour suppressor by the Wnt signalling pathway in human gastric adenocarcinoma.

E3 ubiquitin ligases regulate a variety of biological processes through the ubiquitin-proteasome system, together with ubiquitin activating enzyme E1 and ubiquitin-conjugating enzyme E2. Previous studies have demonstrated that zinc and ring finger 3 (ZNRF3), which belongs to the E3 ubiquitin ligases family is involved in the Wnt signalling pathway, which plays an important role in causing cancer. However, the expression and function of ZNRF3 in human gastric adenocarcinoma still remains unclear. Immunohistochemical and western blot analysis showed a significant down-regulation of ZNRF3 protein in gastric adenocarcinoma tissues compared with adjacent normal gastric tissues. In addition, there was a correlation between the down-regulation of ZNRF3 and poor tissue differentiation in gastric adenocarcinoma. To investigate the potential function of ZNRF3 in cell proliferation and apoptosis, a gastric cell line SGC7901 was employed. The over-expression of wild-type ZNRF3, which was accomplished by the transient transfection of recombinant pEGFP-ZNRF3 (or empty plasmids as control) into the cell line SGC7901, was confirmed by western blot analysis. Flow-cytometry-based and Cell Counting Kit-8 assays showed that over-expression of wt ZNRF3 induced apoptosis and suppressed proliferation. ZNRF3-overexpressing gastric cells displayed partly attenuated protein levels of beta-catenin and TCF-4 compared with those transfected with the empty plasmid. Our study demonstrates a novel gastric adenocarcinoma suppressor and reveals that ZNRF3 inhibits gastric cancer cell growth and promotes the cell apoptosis by affecting the Wnt/beta-catenin/TCF signalling pathway.

Design, synthesis and pharmacological evaluation of novel tacrine-caffeic acid hybrids as multi-targeted compounds against Alzheimer's disease.

A novel series of tacrine-caffeic acid hybrids (5a-f) were designed and synthesized by combining caffeic acid (CA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to CA. Among these compounds, 5e showed the highest selectivity in inhibiting acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Enzyme kinetic study had suggested that 5e binds to both catalytic (CAS) and peripheral anionic sites (PAS) of AChE. Moreover, compound 5e also inhibited self- or AChE-induced ß-amyloid(1-40) aggregation, as well as had potent neuroprotective effects against H(2)O(2)- and glutamate- induced cell death with low toxicity in HT22 cells.

Development of a microplate reader compatible microfluidic chip for ELISA.

We report a novel microfluidic device use for sandwich enzyme-linked immunoassay assay (ELISA). The related procedures including the introduction of reagents, dilution and distribution of samples, as well as immobilization of enzyme can be readily carried out on a poly (dimethylsiloxane) (PDMS) chip. Particularly, this microfluidic chip comprising of two distinct parallel units, and has an identical dimension as a conventional microtiter plate, which offers access to the directly quantitative detection by the microplate reader. Gradient-concentration reacting solutions at six different concentrations level generated by the microfluidic channel network are simultaneously transported to 24 reaction chambers to form enzymatic products. Alkaline phosphatase (ALP), 4-methylumbelliferyl phosphate (4-MUP) and KH(2)PO(4) are used as enzyme-substrate-inhibitor model, to demonstrate the utility of the developed microchip-based enzyme inhibitor assay. Various conditions such as the surface treatment of chip channels, fluids velocities, substrate concentration, and buffer pH are investigated. The present microfluidic device for ELISA holds several advantages, for instance frugal usage of samples and reagents, less of operating time, favorably integrated configuration, ease of manipulation, and could be explored to a variety of high throughput drug screening.

Tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-ß-mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo.

We have previously synthesized a series of hybrid compounds by linking ferulic acid to tacrine as multifunctional agents based on the hypotheses that Alzheimer's disease (AD) generates cholinergic deficiency and oxidative stress. Interestingly, we found that they may have potential pharmacological activities for treating AD. Here we report for the first time that tacrine-6-ferulic acid (T6FA), one of these compounds, can prevent amyloid-ß peptide (Aß)-induced AD-associated pathological changes in vitro and in vivo. Our results showed that T6FA significantly inhibited auto- and acetylcholinesterase (AChE)-induced aggregation of Aß(1-40)in vitro and blocked the cell death induced by Aß(1-40) in PC12 cells. In an AD mouse model by the intracerebroventricular injection of Aß(1-40), T6FA significantly improved the cognitive ability along with increasing choline acetyltransferase and superoxide dismutase activity, decreasing AChE activity and malondialdehyde level. Based on our findings, we conclude that T6FA may be a promising multifunctional drug candidate for AD.

[Advances on enzymes and enzyme inhibitors research based on microfluidic devices].

With the continuous development in microfluidic fabrication technology, microfluidic analysis has evolved from a concept to one of research frontiers in last twenty years. The research of enzymes and enzyme inhibitors based on microfluidic devices has also made great progress. Microfluidic technology improved greatly the analytical performance of the research of enzymes and enzyme inhibitors by reducing the consumption of reagents, decreasing the analysis time, and developing automation. This review focuses on the development and classification of enzymes and enzyme inhibitors research based on microfluidic devices.