Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex.

Alkaloids having acetylcholinesterase (AChE) inhibitory activity are commonly found in traditional Chinese medicine (TCM); for example, berberine from Coptis chinensis, galantamine from Lycoris radiata, and huperzine A from Huperzia serrata. In practice of TCM, Stephaniae Tetrandrae Radix (STR) is often combined with Coptidis Rhizoma (CR) or Phellodendri Chinensis Cortex (PCC) as paired herbs during clinical application. Fangchinoline from STR and coptisine and/or berberine from CR and/or PCC are active alkaloids in inhibiting AChE. The traditional usage of paired herbs suggests the synergistic effect of fangchinoline-coptisine or fangchinoline-berberine pairing in AChE inhibition. HPLC was applied to identify the main components in herbal extracts of STR, CR, and PCC, and the AChE inhibition of their main components was determined by Ellman assay. The synergism of herb combination and active component combination was calculated by median-effect principle. Molecular docking was applied to investigate the underlying binding mechanisms of the active components with the AChE protein. It was found that fangchinoline showed AChE inhibitory potency; furthermore, fangchinoline-coptisine/berberine pairs (at ratios of 1:5, 1:2, 1:1, and 2:1) synergistically inhibited AChE; the combination index (CI) at different ratios was less than one when Fa = 0.5, suggesting synergistic inhibition of AChE. Furthermore, the molecular docking simulation supported this enzymatic inhibition. Therefore, fangchinoline-coptisine/berberine pairs, or their parental herbal mixtures, may potentially be developed as a possible therapeutic strategy for Alzheimer's patients.

MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis.

BACKGROUND: MiR-125b functions as an oncogene in many cancers; however, its clinical significance and molecular mechanism in gastric cancers have never been sufficiently investigated. Here, we elucidated the functions and molecular regulated pathways of MiR-125b in gastric cancer. METHODS: We investigated MiR-125b expression in fresh tissues from 50 gastric cancer patients and 6 gastric cancer cell lines using RT-PCR, and explored its prognostic value by hybridizing MiR-125b in situ for 300 clinical gastric tumor tissues with pathological diagnosis and clinical parameters. The effects of MiR-125b on gastric cancer cells and downstream target genes and proteins were analyzed by MTT, transwell assay, RT-PCR, and western blot on the basis of silencing MiR-125b in vitro. Luciferase reporter plasmid was constructed to demonstrate MiR-125b's direct target. RESULTS: MiR-125b was upregulated in gastric cancer tissues and cell lines, and significantly promoted cellular proliferation, migration, and invasion by downregulating the expression of PPP1CA and upregulating Rb phosphorylation. MiR-125b expression was significantly correlated with tumor size and depth of invasion, lymph nodes, distant metastasis, and TNM stage. The high-MiR-125b-expression group had a significantly poorer prognosis than the low-expression group (P < 0.05) in stages I, II, and III, and the 5-year survival rate in of the high-expression group was significantly lower than that of the low-expression group. CONCLUSIONS: MiR-125b functions as an oncogene by targeting downregulated PPP1CA and upregulated Rb phosphorylation in gastric cancer. MiR-125b not only promotes cellular proliferation, migration, and invasion in vitro, but also acts as an independent prognostic factor in gastric cancer.

Sirtuin 1 Activator SRT1720 Protects Against Lung Injury via Reduction of Type II Alveolar Epithelial Cells Apoptosis in Emphysema.

In chronic obstructive pulmonary disease (COPD), two major pathological changes that occur are the loss of alveolar structure and airspace enlargement. Type II alveolar epithelial cells (AECII) play a vital role in maintaining alveolar homeostasis and lung tissue repair. Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase, regulates many pathophysiological processes including inflammation, apoptosis, cellular senescence and stress resistance. The main aim of this study was to investigate whether SRT1720, a pharmacological SIRT1 activator, could protect against AECII apoptosis in rats with emphysema caused by cigarette smoke exposure and intratracheal lipopolysaccharide instillation in vivo. During the induction of emphysema in rats, administration of SRT1720 improved lung function including airway resistance and pulmonary dynamic compliance. SRT1720 treatment up-regulated the levels of surfactant protein (SP)A, SPC, SIRT1 and forkhead box O 3, increased SIRT1 activity, down-regulated the level of p53 and inhibited AECII apoptosis. Lung injury caused by emphysema was alleviated after SRT1720 treatment. SRT1720 could protect against AECII apoptosis in rats with emphysema and thus could be used in COPD treatment.

Expression of galectin-1 in carcinoma-associated fibroblasts promotes gastric cancer cell invasion through upregulation of integrin ß1.

Increased expression of galectin-1 (Gal-1) in carcinoma-associated fibroblasts (CAFs) has been reported to correlate with progression and prognosis in many cancers. However, rarely have reports sought to determine whether high Gal-1 expression in CAFs in gastric cancer is involved in the tumor process, and the specific mechanism by which it promotes the evolution of gastric cancer is still unknown. In this study, we cultured gastric cancer CAFs, which showed strong expression of Gal-1, and established a co-culture system of CAFs with gastric cancer cells. Specific siRNA and in vitro migration and invasion assays were used to explore the effects of the interaction between Gal-1 expression of CAFs and gastric cancer cells on cell migration and invasion. We found that the overexpression of Gal-1 in CAFs enhanced gastric cancer cell migration and invasion, and these stimulatory effects could be blocked by specific siRNA which reduced the Gal-1 expression level. A set of cancer invasion-associated genes were then chosen to identify the possible mechanism of Gal-1-induced cell invasion. Among these genes, integrin ß1 expression in cancer cells was considered to be associated with Gal-1 expression. Pre-blocking of the integrin ß1 expression in gastric cancer cells with siRNA could interrupt the invasion-promoting effect of CAFs with high Gal-1 expression. Furthermore, immunohistochemical assay confirmed a positive correlation between Gal-1 and integrin ß1 expression. Our results showed that high expression of Gal-1 in CAFs might facilitate gastric cancer cell migration and invasion by upregulating integrin ß1 expression in gastric cancer.

Comparison of corneal flap morphology using AS-OCT in LASIK with the WaveLight FS200 femtosecond laser versus a mechanical microkeratome.

PURPOSE: To evaluate and compare the thickness and the morphology of femtosecond and mechanical microkeratome LASIK flaps using anterior segment optical coherence tomography (AS-OCT). METHODS: Bilateral LASIK was performed in 132 eyes from 61 myopic patients. Flaps were created in 72 eyes using the WaveLight FS200 femtosecond laser (Wave-Light GmbH, Erlangen, Germany) and in 50 eyes using the Moria microkeratome (Moria SA, Antony, France). AS-OCT was used 1 week postoperatively to evaluate the thickness of 17 points across each flap, which were 0, 2, and 3.5 mm to the corneal vertex on the horizontal, vertical, 45°, and 135° meridians. RESULTS: The mean central flap thickness was 105.53 ± 5.86 µm in the WaveLight group and 132.96 ± 13.91 µm in the Moria group (P < .001). The difference between the achieved and the intended flap thickness (accuracy) was 6.17 ± 3.98 and 23.60 ± 12.64 µm, respectively (P < .001). The standard deviation within individual flap (uniformity) was smaller in the WaveLight group. The symmetry and regularity were also better in the WaveLight group. Flap morphology showed a more regular planar shape in the WaveLight group and a meniscus shape in the Moria group. CONCLUSIONS: AS-OCT showed that the flaps created by the WaveLight femtosecond laser were more accurate, reproducible, and uniform than those created by the Moria microkeratome.

[Risk factors and management for inadvertent stromal dissection of Epi-LASIK].

OBJECTIVE: To investigate the risk factors of inadvertent cornea stromal dissection during mechanical epikeratome separation of the corneal epithelium using a Moria Epi-keratome and to explore the best procedure for the treatment of this complication. METHODS: We retrospectively reviewed inadvertent stromal dissections in central or peri-central areas of the cornea during mechanical epi-keratome separation of the corneal epithelium from a series of 708 eyes (355 patients) who received myopic Epi-laser-assisted in situ keratomileusis (Epi-LASIK) procedures during the past five years. The best spectacle corrected visual acuities (BCVA) and topographies at the final follow-up after the last procedures were compared. RESULTS: From the total of treated eyes, 4 eyes of 4 patients (0.56%) suffered inadvertent stromal dissection. In two of them, an excimer laser ablation under the flaps was performed immediately. One patient was treated with LASIK 6 month after the first procedure and another one received an excimer laser photo-therapeutic keratectomy (PTK) removing the corneal epithelium and photorefractive keratectomy (PRK) for refractive correction 1 month after Epi-LASIK. Postoperatively, BCVA lost one line in one eye which received immediate excimer laser ablation under complicated flap. Topography demonstrated irregularity corresponding to the site of stromal dissection. Two eyes (one received immediate excimer laser ablation and another received LASIK 6 month after stromal dissection) recovered to the pre-Epi-LASIK BCVA. One eye that received PTK and PRK 1 month after Epi-LASIK obtained an increase of one line in BCVA. Topography in all three eyes showed regular patterns in the middle of the cornea. CONCLUSIONS: Stromal dissection during mechanical separation of the corneal epithelium with Moria Epi-K epikeratome is a potential complication of Epi-LASIK. One month postoperative PTK and PRK turned out to be the option of proper management for good recovery without severe visual impairment.

Novel phenylpropanoids and isoflavone glycoside are isolated and identified from the carob pods (Ceratonia siliqua L.).

Two new phenylpropanoids (1 and 2) and one new isoflavone glycoside (3), along with nine known compounds (4 - 12), were isolated from the pod of Ceratonia siliqua L. Their chemical structures were elucidated based on extensive spectroscopic analyses (1 D and 2 D NMR, UV, IR, and HRESIMS) and compared with the literature data. In addition, all isolated compounds were evaluated in vitro for inhibitory activity against acetylcholinesterase (AChE). Compounds 4, 5, and 12 showed inhibitory activity against acetylcholinesterase (AChE) with IC50 values ranging from 15.0 to 50.2 µM.

REG4 contributes to the invasiveness of pancreatic cancer by upregulating MMP-7 and MMP-9.

Recent studies have shown that overexpression of regenerating gene family member 4 (REG4) is associated with the initiation and progression of pancreatic cancer. In our study, we explored the role of REG4 in the invasion of pancreatic cancer. Real-time PCR and Western blot analysis were used to determine REG4 expression in pancreatic cancer cell lines. An MTT assay was carried out to test the effect of REG4 on the growth of pancreatic cancer cells. The involvement of REG4 in cancer cell invasion was examined by Transwell invasion assay. Two MMPs, MMP-7 and MMP-9, were identified from a pool of candidate genes as being related to REG4-induced cell invasion by PCR and Western blotting. Immunohistochemistry was used to confirm the correlation between REG4 and the two MMPs. High expression of REG4 was found in BXPC-3 cells and its culture media. But in PANC-1 and ASPC-1 cell lines, REG4 expression levels were very low, and no detectable protein was found in the culture medium. The MTT and Transwell invasion assays showed that recombinant REG4 protein and BXPC-3 conditioned media significantly promoted the proliferation and invasiveness of pancreatic cancer cells. It was also shown that MMP-7 and MMP-9 are upregulated by REG4 induction using real-time PCR and Western blotting analysis. Immunohistochemical study further verified this result. In conclusion, REG4 promotes not only growth but also in vitro invasiveness of pancreatic cancer cells by upregulating MMP-7 and MMP-9.

Comparison of Tear cytokines and clinical outcomes between off-flap and on-flap epi-LASIK with mitomycin C.

PURPOSE: To compare tear cytokines and clinical outcomes between off-flap and on-flap epi-LASIK eyes and explore the possible mechanism for the clinical differences. METHODS: This double-masked, randomized study enrolled 18 myopic patients who underwent off-flap epi-LASIK with mitomycin C (MMC) in 1 eye and on-flap epi-LASIK with MMC in the contralateral eye. Tears were collected from each eye preoperatively and 2 hours, 1 day, and 5 days postoperatively. Concentrations of multiple tear cytokines were measured by a multiplex immunobead assay. Uncorrected distance visual acuity (UDVA), refraction, haze scores, pain scores, and percentage of corneal epithelial healing were evaluated. RESULTS: Compared with the on-flap group, the off-flap group had outcomes of better UDVA and higher percentages of epithelial healing at 5 days after surgery (P<.001) and lower levels of haze at 1 month after surgery (P=.049). Preoperatively, no significant differences were noted in the release rate of all tear cytokines between groups. At 2 hours postoperatively, the release rate of tear basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF-BB), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in the off-flap group were significantly lower than those in the on-flap group (P=.011, .017, .048, and .041, respectively). CONCLUSIONS: Off-flap epi-LASIK with MMC offers faster corneal epithelial healing and visual recovery, and temporary less haze than on-flap epi-LASIK with MMC. The lower tear levels of bFGF, PDGF-BB, IL-8, and TNF-α in the offflap group 2 hours after surgery may suggest a possible mechanism for the clinical differences.

Interaction of coagulation factors and tumor-associated macrophages mediates migration and invasion of gastric cancer.

Abundant macrophage infiltration and increased expression of coagulation factors have been observed in cancer patients. The aim of the present study was to determine how the interaction between activated coagulation factors and monocytes/macrophages contributes to gastric cancer (GC) cell migration and invasion. We assessed cytokine/chemokine production of coagulation-factor-treated macrophages by ELISA. The effects of the interaction between coagulation factors and tumor-associated macrophages (TAM) on GC cell migration and invasion were determined by in vitro migration and invasion assay. In addition, we used an in vitro co-culture system of GC cells/TAM treated by coagulation factors to evaluate the effect of coagulation factor/TAM interaction on the human umbilical vein endothelial cell line (HUVEC). We found that the M2-like phenotype of interleukin (IL)-4(high), IL-10(high), transforming growth factor (TGF)-ß(high), tumor necrosis factor (TNF)-α(high) was exhibited when the human monocytic cell line THP-1 was stimulated by coagulation factors III (TF), VIIa (FVIIa) and XIIa (FXIIa). For the migration assay, the GC cells (BGC-823 or SGC-7901) that were co-cultured with activated coagulation factor/TAM both showed increased migration. For the invasion assay, both BGC-823 and SGC-7901 cells co-cultured with TF/TAM showed increased invasion. We also found that TAM activated by coagulation factors could induce vascular endothelial growth factor/MMP-9 expression, which could promote invasion of GC cells. The HUVEC co-cultured with TAM (PMA-treated THP-1 macrophages co-cultured with GC cells) expressed high levels of FXIIa. In conclusion, coagulation factors might facilitate GC cell migration and invasion by transforming macrophages toward TAM-like cells. Interaction of coagulation factors and TAM mediates migration and invasion of GC.

Characterization of a macrophagic-like cell line derived from rabbit fish (Siganus fuscescens): An illustration of anti-inflammatory responses of the herbal extract of Scutellaria baicalensis.

A new cell line was isolated and characterized from the head kidney of Siganus fuscescens (rabbit fish). The new macrophagic-like cell line was named as rabbit fish macrophage (RFM), and which could be sub-cultured for over 50 cycles since the development. RFM cell line was tested for growth in different temperatures and serum concentrations: the best growing condition was optimized at 20% serum under 28 °C. In cultured RFM cells, sequencing of 18S rRNA, as well as immunostaining of cytokeratin and CD 68, confirmed the identity as macrophagic cell of S. fuscescens. Cultured RFM cells were exposed to challenge of inflammation, as triggered by LPS, showing highly sensitive responses to inflammation, including release of nitric oxide, expression of cytokine, and activation of phagocytosis. The water extract of aerial part of Scutellaria baicalensis, named as SBA, has been shown anti-inflammatory property in S. fuscescens fish. In order to extend the application of SBA in aquaculture, the extract and its effective flavonoids, i.e. baicalin and scutellarin, were applied in LPS-treated RFM cells. Application of SBA extract, baicalin or scutellarin, inhibited the expressions of LPS-induced inflammatory cytokines, i.e. IL-1ß, TNF-α, as well as the signaling of transcription factor NF-κB. The results support the established RFM cell line could be an ideal in vitro model in drug screening relating to inflammation. Additionally, the notion of SBA herbal extract in fish aquaculture is supported by its efficacy against inflammation.

Anterior segment optical coherence tomography measurement of flap thickness after myopic LASIK using the Moria one use-plus microkeratome.

PURPOSE: To analyze the accuracy and consistency of corneal flap thickness created in myopic LASIK using the Moria One Use-Plus microkeratome compared with the Moria M2 Single Use 90-microm microkeratome. METHODS: Bilateral LASIK was performed in 68 myopic patients. Flaps were created using the One Use-Plus microkeratome in 82 eyes (41 patients) and the M2 90-microm microkeratome in 54 eyes (27 patients). Flap complications and visual outcomes were evaluated. Horizontal "High Res. Corneal" scan pattern of anterior segment optical coherence tomography (AS-OCT) was applied to measure flap thickness at five locations (0, +/-2, and +/-3.5 mm from the corneal vertex) on the first postoperative day. RESULTS: No significant differences were noted in flap complications and visual outcomes between groups. The central flap thickness was dramatically thinner in the One Use-Plus group (114.7+/-10.1 microm and 109.4+/-11.0 microm for right and left eyes, respectively) than in the M2 group (155.6+/-14.8 microm and 151.6+/-12.5 microm for right and left eyes, respectively) (P<.001). The One Use-Plus did not show a markedly better uniformity than the M2; the variation was mainly observed in the periphery. Multiple linear regression showed that for the One Use-Plus, the steeper the preoperative keratometry, the thicker the flap thickness, and for the M2, the thicker the preoperative pachymetry, the thicker the flap (P<.1). CONCLUSIONS: The One Use-Plus and M2 microkeratomes have similar safety and efficacy. The flap created by the One Use-Plus was much thinner than the flap created with the M2; however, the One Use-Plus can not realize a fully planar-shaped flap.

Shexiang Baoxin Pill, a Traditional Chinese Herbal Formula, Rescues the Cognitive Impairments in APP/PS1 Transgenic Mice.

BACKGROUND: Shexiang Baoxin Pill (SBP), a formulated traditional Chinese medicine (TCM), has been widely used to treat cardiovascular diseases for years. This herbal mixture has been shown to promote differentiation of cultured neuronal cells. Here, we aimed to investigate the effects of SBP in attenuating cognitive impairment in APP/PS1 transgenic mice. METHODS: Ethanol and water extracts of SBP, denoted as SBPEtOH and SBPwater, were standardized and applied onto cultured rat pheochromocytoma PC12 cells. The potential effect of SBPEtOH extract in attenuating the cognitive impairments in APP/PS1 transgenic mice was shown by following lines of evidence: (i) inhibition of Aß fibril formation, (ii) suppression of secretions of cytokines, and (iii) improvement of behavioral tests by Morris water maze. RESULTS: SBPwater and SBPEtOH inhibited the formation of ß-amyloid fibrils and protected the Aß-induced cytotoxicity in cultured PC12 cells. In APP/PS1 transgenic mice, the treatment of SBPEtOH inhibited expressions of NO, NOS, AChE, as well as aggregation of Aß. Besides, the levels of pro-inflammatory cytokines were suppressed by SBP treatment in the transgenic mice. Importantly, the behavioral tests by Morris Water maze indicated that SBP attenuated cognitive impairments in APP/PS1 transgenic mice. CONCLUSION: The current result has supported the notion that SPB might ameliorate the cognitive impairment through multiple targets, suggesting that SBP could be considered as a promising anti-AD agent.

Shexiang Baoxin Pill, a Formulated Chinese Herbal Mixture, Induces Neuronal Differentiation of PC12 Cells: A Signaling Triggered by Activation of Protein Kinase A.

Background: Shexiang Baoxin Pill (SBP) is a well-known composite formula of traditional Chinese medicine (TCM), which is commonly used today in treating cardiovascular diseases. SBP consists of seven materials thereof, including Moschus, extract of Ginseng Radix et Rhizoma, Bovis Calculus Artifactus, Cinnamomi Cortex, Styrax, Bufonis Venenum, and Borneolum Syntheticum. Here, we are investigating the potential roles of SBP in inducing neuron differentiation, i.e., seeking possible application in neurodegenerative diseases. Methods: Water and ethanol extracts of SBP, denoted as SBPwater and SBPEtOH, respectively, as well as its individual herbal materials, were standardized and applied onto cultured rat pheochromocytoma PC12 cells. The potential effect of SBP extracts in neuronal differentiation was suggested by following parameters: (i) induction of neurite outgrowth of PC12 cells, (ii) increase of neurofilament expression, and (iii) activation of transcription of neurofilament. Results: The treatments of SBPwater and SBPEtOH, or extracts from individual herbal materials, with or without low concentration of nerve growth factor (NGF), could potentiate the differentiation of cultured PC12 cells. The differentiation was indicated by increase of neurite outgrowth, as well as expression of neurofilaments. In addition, application of H89, a protein kinase A (PKA) inhibitor, suppressed the SBP-induced neurofilament expressions, as well as the phosphorylation of cAMP-responsive element binding protein (CREB) in cultures. Conclusion: SBP is proposed to possess trophic activity in modulating neuronal differentiation of PC12 cells, and this induction is shown to be mediated partly by a cAMP-PKA signaling pathway. These results indicate the neurite-promoting SBP could be useful in developing potential drug in treating or preventing neurodegenerative diseases.

[Comparison of laser in situ keratomileusis and laser-assisted subepithelial keratectomy for myopia more than -10.00 diopters].

OBJECTIVE: To compare the visual and refractive outcomes of laser in situ keratomileusis (LASIK) and laser-assisted subepithelial keratectomy (LASEK) in the treatment of severe myopia. METHODS: LASEK and LASIK were respectively performed on 165 eyes of 100 patients with super high myopia by using the Allegretto Wavelight-Wave 1,007 excimer laser, of which 10(6) eyes (62 patients) were treated with LASEK and 59 eyes (38 patients) with LASIK. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), remaining refractive error, corneal haze and complications were followed up in both groups for 12 months. RESULTS: At the end of 6 months and 12 months no significant statistic difference between LASEK and LASIK group in the clinical outcomes of refractive corrections (mean spherical equivalent, MSE). At the end of 1 week and 1 month postoperatively, UCVA in the LASIK eyes was better than in LASEK eyes. At the end of 3, 6, 12 months, it was almost the same in these two groups. The percentage of eyes with UCVA better than 1.0 (47.8% in LASEK, 52.5% in LASIK) was higher in LASEK group. There was no significant difference between the two groups in the percentage of eyes losing one or more lines of BSCVA in Snellen visual acuity chart. At the end of 12 months, the mean SE was within +/-0.5D of emmetropia in 9 eyes (13.2%) in the LASEK group and 11 eyes (18.6%) in the LASIK group and within +/-1.0D of emmetropia in 36 eyes (52.9%) in the LASEK group and 28 eyes (47.5%) in the LASIK group, respectively, the between-group differences were not statistically significant (P>0.05). There were more complaints of postoperative pain and discomfort after LASEK procedure. No severe vision threatening complications in these two groups were found. CONCLUSION: Both LASIK and LASEK are safe and effective in treating eyes with severe myopia.

Upregulation of miR-101 enhances the cytotoxic effect of anticancer drugs through inhibition of colon cancer cell proliferation.

This study investigated the effect of miR-101 on proliferation, migration, invasion, and chemotherapy sensitivity in colon cancer cell lines HT-29 and RKO. MicroRNAs are a class of small noncoding RNA molecules, which play important roles in diverse biological processes of human cancers, such as carcinogenesis, development, differentiation, and apoptosis. The expression of miR-101 in colon cancer and adjacent non-tumor tissues were examined by quantitative real-time polymerase chain reaction. The expression of miR-101 was upregulated by recombinant adenovirus Ad-miR-101. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cloning methods. Cell migration and invasion potential were examined using Transwell migration and Matrigel invasion chamber assays. Drug sensitivity to 5-fluorouracil (5-FU) and cisplatin (DDP) was explored using MTT assays and l acridine orange/ethidium bromide double staining. The expression of miR-101 decreased in colon cancer tissues compared with adjacent non-tumor tissues. The upregulated expression of miR-101 suppressed cell proliferation and inhibited cell migration and invasion in HT-29 and RKO colon cancer cell lines. The overexpression of miR-101 promoted the inhibitory effect of 5-FU and DDP on HT-29 cells. The expression of miR-101 was downregulated in colon cancer. The upregulated expression of miR-101 inhibited proliferation and migration, and increased the sensitivity of colon cancer cells to chemotherapy.

PHD3 affects gastric cancer progression by negatively regulating HIF1A.

Prolyl hydroxylase 3 (PHD3) is widely accepted as a tumor suppressor; however, the expression of PHD3 in various cancer types remains controversial. The present study aimed to investigate the association between PHD3 expression and the clinicopathological features of gastric cancer using reverse transcription­quantitative polymerase chain reaction and immunohistochemistry. The effects of PHD3 in gastric cancer cell lines were assessed using western blot analysis and transwell migration assays. The present results revealed that PHD3 expression was increased in adjacent non­cancerous tissue compared with in gastric cancer tissue, and PHD3 overexpression was correlated with the presence of well­differentiated cancer cells, early cancer stage classification and the absence of lymph node metastasis. In vitro experiments demonstrated that PHD3 may act as a negative regulator of hypoxia­inducible factor­1α and vascular endothelial growth factor, both of which participate in tumor angiogenesis. In conclusion, the present results suggested that PHD3 may act as a tumor suppressor in gastric cancer. Therefore, the targeted regulation of PHD3 may have potential as a novel therapeutic approach for the treatment of patients with gastric cancer.

MicroRNA-145-5p inhibits gastric cancer invasiveness through targeting N-cadherin and ZEB2 to suppress epithelial-mesenchymal transition.

MicroRNA (miR)-145-5p has been reported to function as a suppressor of cancer and plays an important role in cancer invasiveness. Epithelial-mesenchymal transition (EMT) is an important process in cancer invasion and migration. However, the involvement of miR-145-5p in EMT in human gastric cancer (GC) remains unclear. In this study, we aimed to investigate the molecular mechanisms by which miR-145-5p regulates EMT in GC invasiveness. We used quantitative real-time polymerase chain reaction to investigate the miR-145-5p expression level in GC and matched normal tissues. The effects of miR-145-5p on GC cell invasion and migration abilities were evaluated using Transwell models. The relationships among miR-145-5p and zinc-finger E-box binding homeobox 2 (ZEB2), E-cadherin, and N-cadherin were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses. miR-145-5p levels in primary GC tissues obtained from 60 patients were significantly downregulated, compared to those in paired normal tissues. Lauren classification, depth of tumor invasion, lymph node metastasis, lymphatic invasion, and tumor-node-metastasis stage were associated with miR-145-5p expression. miR-145-5p inhibits the expression of the candidate target gene ZEB2 to delay the invasion and migration of GC cells. ZEB2 acts as transcriptional repressor of E-cadherin, while miR-145-5p is known to suppress N-cadherin directly to regulate EMT. Therefore, we concluded that miR-145-5p may target N-cadherin and ZEB2 directly to influence EMT.

Downregulation of ALDOB is associated with poor prognosis of patients with gastric cancer.

OBJECTIVES: To examine the expression of ALDOB in gastric cancer (GC) tissue and to reveal its potential clinicopathological and prognostic significance. MATERIALS AND METHODS: We screened for genes that were differentially expressed between GC and nontumor tissues using a microarray, specifically the Affymetrix U133 Plus 2.0 Array platform. We then verified the transcriptional and translational levels of ALDOB by performing quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). In addition, a merged data set based on the Gene Expression Omnibus was generated and a survival analysis performed. RESULTS: The microarray analysis revealed that ALDOB was downregulated (more than sevenfold) in GC compared with nontumor tissue. Both qRT-PCR and IHC validated the decrease of ALDOB in GC tissue. Moreover, we found that the expression of ALDOB was significantly related to tumor-invasion depth, lymph-node metastasis, distant metastasis, and TNM stage. The survival analysis, based on the IHC and merged data set, indicated that the overall survival was better in patients with high ALDOB expression. The Cox regression analysis showed that ALDOB expression was an independent prognostic factor for GC. CONCLUSION: The expression of ALDOB in GC tissue was significantly related to the clinicopathological features and prognosis of the disease, thus suggesting that ALDOB could act as a novel molecular marker for GC.

[Clinical study of higher order wavefront aberrations with a Tscherning aberrometer].

OBJECTIVE: To study the higher order aberrations of emmetropic and ametropic eyes with wavefront aberrometer. METHODS: Forty of cases 77 emmetropic and ametropic eyes were measured with an aberrometer based on Tscherning's principle with the pupils dilated. The Zernike coefficients and root mean square values of wavefront aberrations up to the 6th order were recorded and statistically analyzed. RESULTS: The C06, C07, C08, C12, C13, C14, C24, C26, and C27 were significantly different from zero under 7 mm pupil size and the C06, C10, C12, C23, and C24 were significantly different from zero under 4 mm pupil size. There was no significant difference of higher order wavefront aberrations between emmetropic and ametropic eyes. Comparing the age of 40 years or less with the age over 40 years, there were significant differences in RMS3 between the two under 7 mm pupil size, and statistical differences in RMS6 and RMSh between the two under 4 mm pupil size. CONCLUSION: There are certain higher order wavefront aberrations in the normal human eyes, especially with the pupils dilated. No differences are found in higher order aberrations between emmetropic and ametropic eyes. The higher order aberrations of the age over 40 years are more than those of the age of 40 years or younger.