No abstract

To investigate the expression of interleukin 17 (IL-17) in serum and tumor tissues, and evaluate the correlation between IL-17 and clinical characteristics from patients with gastric cancer. From January 2009 to January 2010, total 50 patients with gastric cancer and 50 healthy controls were enrolled. The patients included 32 males and 18 females with average age of (62.05 ± 11.98) years. The concentration of serum IL-17 was detected by ELISA. Intratumoral IL-17 expression and microvessel density (MVD) were examined by immunohistochemical staining. Compared with healthy controls, patients with gastric cancer had higher levels of IL-17 in serum (p < 0.01) and cancer tissues. High expression of IL-17 was associated with high MVD (p < 0.01). IL-17 in cancer tissues was associated with the clinical stage of the tumors (p < 0.01) and lymph node metastasis (p < 0.05). No statistically significant correlation between the serum IL-17 and the clinical pathological features was found. Increased expression of IL-17 was seen in patient with gastric cancer. IL-17 may be involved in the progression of gastric cancer by promoting angiogenesis in tumor microenvironment.

Objective. To improve students' learning and develop learning skills in pharmacy education. Methods.A novel teaching method STQD, composed of Self-study, Test, Question and Discussion sessions, uses self-, peer-, co-learning, active learning, inductive teaching, and formative assessment to promote student-centered teaching in pharmacy education. The intervention has been carried out within courses focusing on instrumental analysis and analytical chemistry. In a four-year study, qualitative and quantitative approaches were employed to evaluate the effectiveness of the novel teaching method in facilitating students' learning. Conclusion. The use of STQD in an integrated basic science curriculum has the potential to develop students' learning skills and improve students' learning in pharmacy education.

These data show, for the first time, functional divergence of VA action on a single protein target. The VAs in this study fall into two distinct groups with respect to their effects on these receptors. This grouping parallels the chemistry of these compounds. Our results support the involvement of multiple protein domains in the mechanism of VA modulation of GABA and glycine receptors.

OBJECTIVE:Cigarette smoke extracts (CSE) could promote esophageal squamous cell carcinoma (ESCC) through upregulation of cyclooxygenase-2 (COX-2) expression. Promoter methylation mediates the transcriptional modulation of the COX-2 gene. The aim of the study was to explore whether COX-2 promoter methylation regulated COX-2 expression and functional activity in ESCC exposed to CSE. METHODS:The methylation status of COX-2 promoter in two human ESCC cell lines, EC109 and TE-1, was examined using bisulfite sequencing analysis. COX-2 mRNA and protein expression were detected by reverse-transcription polymerase chain reaction and Western blot. Prostaglandin E2 (PGE2) was examined by enzyme linked immunosorbent assay (ELISA). RESULTS:The promoter was hypermethylated in TE-1 which had a low level of COX-2 expression and was hypomethylated in EC109 with a relatively high level of COX-2 expression. Stimulation by cigarette smoke ethanol extract (EE) resulted in increased COX-2 expression in EC109, but not in TE-1. Treatment with 5-aza-2'-deoxycytidine (5-aza-DC) demethylated the promoter and upregulated COX-2 expression as well as PGE2 production in TE-1, especially followed by EE stimulation. No significant effect was observed in EC109. CONCLUSION:These findings suggest that promoter methylation may be one of the mechanisms regulating COX-2 expression in ESCC in response to stimulation of CSE.KEY WORD: cigarette smoke, cyclooxygenase-2, esophageal neoplasm, methylation. INTRODUCTIONEsophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer and the fourth most common cause of cancer death in China. 1 Great efforts have been made since the etiology of ESCC has not been fully elucidated. Cigarette smoke contains over 3000 chemicals, many of which have been identified as carcinogens and are known to initiate and promote tumorigenesis.2 Epidemiological researches have shown that cigarette smoking is one of the risk factors Correspondence to: Shu Tian ZHANG, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Road, Xicheng District, Beijing 100050, China. Email: zhangxym2006@tom.com Xin Ying MENG and Sheng Tao ZHU contributed equally to this paper. 2012; 13; 208-213 doi: 10.1111/j.1751-2980.2012.00578.x 208 for the development of ESCC. 3,4 The chemicals may promote the formation of DNA adduct and modulate cell proliferation, apoptosis and angiogenesis in carcinogenesis. 5 However, the mechanism of cigarette smoke in ESCC carcinogenesis is still unclear. Journal of Digestive DiseasesCyclooxygenase-2 (COX-2) is a rate-limiting enzyme involved in the conversion of arachidonic acid to prostaglandin (PG). COX-2 expression can be induced by a variety of stimuli, such as mitogens, cytokines and growth factors. The overexpression of COX-2 has been observed in ESCC and its premalignant lesions, 6,7 which suggests that COX-2 may be associated with the carcinogenesis and/or the progression of ESCC. Our recent study reported that cigarette smoke could activa...

Background: More and more elderly patients are being diagnosed with arteriovenous malformation (AVM) in this global aging society, while the treatment strategy remains controversial among these aging population. This study aimed to clarify the long-term outcomes of elderly AVMs after different management modalities.Methods: The authors retrospectively reviewed 71 elderly AVMs (&gt;60 years) in two tertiary neurosurgery centers between 2011 and 2019. Patients were divided into four groups: conservation, microsurgery, embolization, and stereotactic radiosurgery (SRS). The perioperative complications, short-term and long-term neurological outcomes, obliteration rates, annualized rupture risk, and mortality rates were compared among different management modalities in the ruptured and unruptured subgroups. Kaplan-Meier survival analysis was employed to compare the death-free survival rates among different management modalities. Logistic regression analyses were conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CI) for predictors of long-term unfavorable outcomes (mRS &gt; 2).Results: A total of 71 elderly AVMs were followed up for an average of 4.2 ± 2.3 years. Fifty-four (76.1%) presented with hemorrhage, and the preoperative annualized rupture risk was 9.4%. Among these patients, 21 cases (29.6%) received conservative treatment, 30 (42.3%) underwent microsurgical resection, 13 (18.3%) received embolization, and 7 (9.9%) underwent SRS. In the prognostic comparison, the short-term and long-term neurological outcomes were similar between conservation and intervention both in the ruptured and unruptured subgroups (ruptured: p = 0.096, p = 0.904, respectively; unruptured: p = 0.568, p = 0.306, respectively). In the ruptured subgroup, the intervention cannot reduce long-term mortality (p = 0.654) despite the significant reduction of subsequent hemorrhage than conservation (p = 0.014), and the main cause of death in the intervention group was treatment-related complications (five of seven, 71.4%). In the logistic regression analysis, higher admission mRS score (OR 3.070, 95% CI 1.559–6.043, p = 0.001) was the independent predictor of long-term unfavorable outcomes (mRS&gt;2) in the intervention group, while complete obliteration (OR 0.146, 95% CI 0.026–0.828, p = 0.030) was the protective factor.Conclusions: The long-term outcomes of elderly AVMs after different management modalities were similar. Intervention for unruptured elderly AVMs was not recommended. For those ruptured, we should carefully weigh the risk of subsequent hemorrhage and treatment-related complications. Besides, complete obliteration should be pursued once the intervention was initiated.Clinical Trial Registration:http://www.clinicaltrials.gov. Unique identifier: NCT04136860

No abstract

Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01-TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC 50 of 0.21 mM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-Ras G12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.