Activation of N-Methyl-D-aspartate receptor contributed to the ultrasonic modulation of neurons in vitro.

Ultrasound stimulation is increasingly used to investigate brain function and treat brain diseases due to its high level of safety and precise spatiotemporal resolution. Therefore, it is crucial to understand the underlying mechanisms involved in ultrasound brain stimulation. In this study, we investigate the role of NMDA receptors in mediating the effects of ultrasound on primary hippocampal neurons in mice. Our results show that ultrasound alone can activate heterologous NMDA receptor subunits, including NR1A, NR2A, and NR2B, in 293T cells, as well as endogenous NMDA receptors in primary neurons. This activation leads to an influx of calcium and an increase in nuclear c-Fos expression in primary neurons that have not been pre-treated with an NMDA receptor inhibitor. In conclusion, our findings demonstrate that NMDA receptors contribute to neuronal activation by ultrasound stimulation in vitro, providing insight into the molecular mechanisms of ultrasound neuromodulation and a new mediator for the sonogenetics technique.

Preparation, characterization, identification, and antioxidant properties of fermented acaí (Euterpe oleracea).

Fermentation technology was used to prepare the acaí (Euterpe oleracea) fermentation liquid. The optimal fermentation parameters included a strain ratio of Lactobacillus paracasei: Leuconostoc mesenteroides: Lactobacillus plantarum = 0.5:1:1.5, a fermentation time of 6 days, and a nitrogen source supplemental level of 2.5%. In optimal conditions, the ORAC value of the fermentation liquid reached the highest value of 273.28 ± 6.55 µmol/L Trolox, which was 55.85% higher than the raw liquid. In addition, the FRAP value of the acaí, as well as its scavenging ability of DPPH, hydroxyl, and ABTS free radicals, increased after fermentation. Furthermore, after fermentation treatment, the microstructure, basic physicochemical composition, amino acid composition, γ-aminobutyric acid, a variety of volatile components, and so on have changed. Therefore, fermentation treatment can significantly improve the nutritional value and flavor of the acaí. This provides a theoretical basis for the comprehensive utilization of acaí.

Corn oligopeptides inhibit Akt/NF-κB signaling pathway and inflammatory factors to ameliorate CCl4 -induced hepatic fibrosis in mice.

In this study, the effect of corn oligopeptides (COPs) with liver protection activity on mice with hepatic fibrosis (HF) induced by carbon tetrachloride (CCl4 ) was studied. It was proved that COPs can ameliorate the liver injury and inflammation caused by CCl4 by histopathology and enzyme-linked immunosorbent assay in mice. The expression of Akt/NF-κB inflammatory pathway was determined by real-time polymerase chain reaction (RT-PCR) and western blotting (WB). The results showed that COPs inhibited the expression of key proteins in the inflammatory pathway. In conclusion, the results of this study suggested that COPs could improve CCl4 -induced HF by improving liver injury, reducing the expression of inflammatory factors, and inhibiting the expression of inflammatory signaling pathways. PRACTICAL APPLICATIONS: The corns around the world are mainly used as animal feed, and the liver protective activity of corn oligopeptides (COPs) is rarely applied to the market. The development of COPs liver protective food can prevent the occurrence of liver-related diseases such as hepatic fibrosis to a certain extent. Developing COPs liver protecting food can improve the utilization value of corn. It is hoped that this study can provide experimental support for the application of COPs in liver protection food.

Effects of topical application of different molecular weight marine fish skin collagen oligopeptides on UVB-induced photoaging rat skin.

OBJECTIVE: The objective of this work was to develop a peptide production process of the exact molecular weight propitious to topical application for cosmetics and to investigate the effects of enzymolysis-derived peptide on UVB-induced photoaging rat skin. METHODS: The chum salmon fish skins were hydrolyzed by alkaline protease and neutral protease and spray-dried at different conditions, and three kinds of molecular weight peptide (MFSOP) were obtained. A total of 66 ICR rats (female, 20 ± 1 g) were randomly divided into eleven groups, including the normal, model, and experimental groups. The three kinds of MFSOP were dissolved at different dosages (5‰, 2.5%, and 5%) and then applied on the ICR hairless back skins prior to exposing UVB irradiation of 3000mJ/cm2 to them 4 h later. After 8 weeks, the rats were killed and the hair-shaved skins were tested for skin moisture, hyaluronic acid, hydroxyproline, antioxidant activity, and RNA expression. RESULTS: Three kinds of MFSOP were obtained, with the average molecular weights of 495.16, 1194.00, and 2032.46 Dalton, respectively. The MFSOPs, especially the MFSOP of average molecular weight of 1194.00 Dalton, played an important role in the recovery of the UVB-injured skin tissue in lock in moisture, in antioxidant activity and in promotion in collagen and elastin protein to some extent. CONCLUSION: MFSOPs, especially MFSOP of average molecular weight of 1194.00 Dalton, derived from enzymolysis are potential materials to apply in cosmetics for the UVB9-induced anti-photoaging activity (lock in moisture, antioxidant activity, and promotion in collagen and elastin protein).

Antioxidant properties and inhibition of angiotensin-converting enzyme by highly active peptides from wheat gluten.

This study aimed to focus on the high-value utilization of raw wheat gluten by determining the potent antioxidant peptides and angiotensin I-converting enzyme (ACE) inhibitory peptides from wheat gluten oligopeptides (WOP). WOP were analyzed for in vitro antioxidant activity and inhibition of ACE, and the identification of active peptides was performed by reversed-phase high-performance liquid chromatography and mass spectrometry. Quantitative analysis was performed for highly active peptides. Five potent antioxidant peptides, Leu-Tyr, Pro-Tyr, Tyr-Gln, Ala-Pro-Ser-Tyr and Arg-Gly-Gly-Tyr (6.07 ± 0.38, 7.28 ± 0.29, 11.18 ± 1.02, 5.93 ± 0.20 and 9.04 ± 0.47 mmol 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) equivalent/g sample, respectively), and five potent ACE inhibitory peptides, Leu-Tyr, Leu-Val-Ser, Tyr-Gln, Ala-Pro-Ser-Tyr and Arg-Gly-Gly-Tyr (half maximal inhibitory concentration (IC50) values = 0.31 ± 0.02, 0.60 ± 0.03, 2.00 ± 0.13, 1.47 ± 0.08 and 1.48 ± 0.11 mmol/L, respectively), were observed. The contents of Leu-Tyr, Pro-Tyr, Tyr-Gln, Ala-Pro-Ser-Tyr, Arg-Gly-Gly-Tyr, and Leu-Val-Ser were 155.04 ± 8.36, 2.08 ± 0.12, 1.95 ± 0.06, 22.70 ± 1.35, 0.25 ± 0.01, and 53.01 ± 2.73 µg/g, respectively, in the WOP. Pro-Tyr, Tyr-Gln, Ala-Pro-Ser-Tyr, Arg-Gly-Gly-Tyr, and Leu-Val-Ser are novel antioxidative/ACE inhibitory peptides that have not been previously reported. The results suggest that WOP could potentially be applied in the food industry as a functional additive.

[Research progress on chemical constituents and biological activities from Turpinia species].

Turpinia species have been used as local Chinese medicines. It has been widely concerned about their antibacterial and anti-inflammatory effects. Modern studies showed that the chemical constituents of Turpina species include flavonoids, triterpenoids, megastigans and phenoli acids. Its pharmacological research mainly focused on antibacterial, anti-inflammatory, antioxidant, analgesic, and immuneregulation effect. In this paper, the chemical compositions and pharmacological activities of Turpinia species were summarized, in order to provide scientific basis for the further development and utilization of Turpinia species.

Prognostic impact and implications of extracapsular lymph node spread in Borrmann type IV gastric cancer.

The purpose of this study was to evaluate the relationship between extracapsular lymph node spread (ECS) and clinicopathology and its influence on the prognosis in patients with Borrmann type IV gastric cancer. Between 2002 and 2014, clinical data were reviewed from 486 patients with Borrmann type IV gastric cancer who underwent curative resection. Of the 486 patients, lymph node metastasis was found in 456. ECS was detected in 213 (46.7%) patients with lymph node metastasis. A positive lymph node with ECS was significantly correlated with the N category, lymphatic/venous invasion, tumor location, and TNM stage. For the whole patients, the mean OS was 34.7 months, and the 5-year OS rate was 15.5%. The 5-year OS rate of node-negative patients was 48%, for node-positive patients without ECS 18.7%, and for node-positive patients with ECS 5.7% (P = 0.000). In a multivariate analysis, adjusted for tumor location, lymphatic/venous invasion, body mass index (BMI), and TNM stages, ECS remained an independent prognostic factor. For patients with the same N category and TNM stage, those with ECS still had a worse survival rate. Recurrent sites were confirmed in 367 patients. The most frequent recurrent site was the peritoneum. There was a significant difference between ECS+ (N = 150) and ECS- (N = 142) patients (P = 0.008). Our results suggested that ECS was an independent prognostic value for Borrmann type IV gastric cancer patients with curative resection and a subgroup indicated a significantly worse long-term survival for patients with the same N or TNM stages. ECS+ was an adverse factor for peritoneal metastasis.

[Sesquiterpenes with anti-metastasis breast cancer activity from Chloranthus henryi].

To study sesquiterpenes with anti-metastasis breast cancer activity from Chloranthus henryi, ten sesquiterpenes ,zedoarofuran (1), chlorajapolide D (2), 4ß, 8ß-dihydroxy-5α(H)-eudesm-7(11)-en-8, 12-olide (3), curcolonol (4), lasianthuslactone A (5), chlomultin C (6), (1E,4Z)-8-hydroxy-6-oxogermacra-1(10), 4, 7(11) -trieno-12, 8-lactone (7), shizukanolide E (8) , shizukanolide F (9) , 9α-hydroxycurcolonol (10), and five bis-sesquiterpenes, shizukaol B (11), shizukaol C (12) , cycloshizukaol A (13) , sarcandrolide B (14) , henriol A(15), were isolated by using different kinds of column chromatography methods from the ethyl acetate part of Ch.henryi and their structures were identified based on spectroscopic methods. Compounds 2, 8, 9, and 10 were obtained from the genus Chloranthus for the first time. Compounds 2, 5, 8-10, 12,and 14 were obtained from this plant for the first time. Some isolated compounds were subjected to evaluate the anti-metastasis breast cancer activity by using pharmacological methods, and only compounds 4, 11, and 12 were potent active.

Friend or Foe? Flipped Classroom for Undergraduate Electrocardiogram Learning: a Randomized Controlled Study.

BACKGROUND: Interpreting an electrocardiogram (ECG) is not only one of the most important parts of clinical diagnostics but also one of the most difficult topics to teach and learn. In order to enable medical students to master ECG interpretation skills in a limited teaching period, the flipped teaching method has been recommended by previous research to improve teaching effect on undergraduate ECG learning. METHODS: A randomized controlled trial for ECG learning was conducted, involving 181 junior-year medical undergraduates using a flipped classroom as an experimental intervention, compared with Lecture-Based Learning (LBL) as a control group. All participants took an examination one week after the intervention by analysing 20 ECGs from actual clinical cases and submitting their ECG reports. A self-administered questionnaire was also used to evaluate the students' attitudes, total learning time, and conditions under each teaching method. RESULTS: The students in the experimental group scored significantly higher than the control group (8.72 ± 1.01 vs 8.03 ± 1.01, t = 4.549, P = 0.000) on ECG interpretation. The vast majority of the students in the flipped classroom group held positive attitudes toward the flipped classroom method and also supported LBL. There was no significant difference (4.07 ± 0.96 vs 4.16 ± 0.89, Z = - 0.948, P = 0.343) between the groups. Prior to class, the students in the flipped class group devoted significantly more time than those in the control group (42.33 ± 22.19 vs 30.55 ± 10.15, t = 4.586, P = 0.000), whereas after class, the time spent by the two groups were not significantly different (56.50 ± 46.80 vs 54.62 ± 31.77, t = 0.317, P = 0.752). CONCLUSION: Flipped classroom teaching can improve medical students' interest in learning and their self-learning abilities. It is an effective teaching model that needs to be further studied and promoted.

Preliminary investigation into application of problem-based learning in the practical teaching of diagnostics.

BACKGROUND: Problem-based learning (PBL) is a pedagogical approach based on problems. Specifically, it is a student-centered, problem-oriented teaching method that is conducted through group discussions. The aim of our study is to explore the effects of PBL in diagnostic teaching for Chinese medical students. METHODS: A prospective, randomized controlled trial was conducted. Eighty junior clinical medical students were randomly divided into two groups. Forty students were allocated to a PBL group and another 40 students were allocated to a control group using the traditional teaching method. Their scores in the practice skills examination, ability to write and analyze medical records, and results on the stage test and behavior observation scale were compared. A questionnaire was administered in the PBL group after class. RESULTS: There were no significant differences in scores for writing medical records, content of interviewing, physical examination skills, and stage test between the two groups. However, compared with the control group, the PBL group had significantly higher scores on case analysis, interviewing skills, and behavioral observation scales. CONCLUSION: The questionnaire survey revealed that PBL could improve interest in learning, cultivate an ability to study independently, improve communication and analytical skills, and good team cooperation spirit. However, there were some shortcomings in systematization of imparting knowledge. PBL has an obvious advantage in teaching with regard to diagnostic practice.

Pilot-scale production of soybean oligopeptides and antioxidant and antihypertensive effects in vitro and in vivo.

Soybean oligopeptides (SOP) with low molecular weights were prepared by two-step enzymatic hydrolysis on a pilot-scale. Peptide and free amino acid contents of SOP were 82.5 ± 1.13 % and 3.7 ± 0.28 % respectively. The molecular weight distribution of SOP was mainly bellow 1,000 Da (85.4 %), 56.7 % of which were 140-500 Da. SOP showed strong stability to proteolytic digestion by pepsin and trypsin. The antioxidant activities and in vitro and in vivo antihypertensive effects of SOP were evaluated. Results showed that SOP exhibited 1,1-diphenyl-2-picrylhydrazyl radical scavenging effect (IC50 = 4.5 ± 0.13 mg/mL), and significantly inhibited lipid peroxidation in linoleic acid oxidation system (IC50 = 1.2 ± 0.09 mg/mL). SOP had potent angiotensin I-converting enzyme inhibitory activity (IC50 = 1.1 ± 0.06 mg/mL), and antihypertensive effect in spontaneously hypertensive rats at a dose of 200 mg/kg. This study indicated that SOP could be a natural antioxidative or antihypertensive compound in the medicine and food industries.

Knockdown of long non-coding RNA HOTAIR suppresses tumor invasion and reverses epithelial-mesenchymal transition in gastric cancer.

BACKGROUND: Over-expression of long non-coding RNA HOTAIR has been reported in several types of cancer. Yet its involvement in gastric cancer (GC) has not been well understood. The aim of present study was to examine the expression pattern of HOTAIR in GC patients, then, explore its role in promoting cancer invasion and underlying molecular mechanism. METHODS: The expression level of HOTAIR in the tumor specimens of GC patients was quantified by Realtime RT-PCR. The correlation between HOTAIR level and clinicopathological factors as well as prognosis was then examined. Down-regulation of HOTAIR by RNA interference was applied to investigate its roles in tumor invasiveness via the view of Epithelial-to-mesenchymal transition (EMT). RESULTS: The expression level of HOTAIR in cancer tissues was higher than that in adjacent noncancerous tissues. Expression level of HOTAIR was significantly correlated with lymph node metastasis and TNM stage. Furthermore, high expression level of HOTAIR was a predictor of poor over-all survival in GC patients. In vitro, inhibition of HOTAIR in GC cells could reduce invasiveness, as well as the expression of MMP1 and MMP3. In addition, suppression of HOTAIR could reverse EMT process. CONCLUSIONS: HOTAIR could act as a potential predictor for over-all survival in patients with GC. Inhibition of HOTAIR could reduce invasiveness and reverse EMT process in GC cells, indicating the potential role of HOTAIR in GC diagnostics and therapeutics.

[Clinicopathological and prognostic analysis of 23 poorly differentiated neuroendocrine carcinomas of the stomach].

OBJECTIVE: To evaluate the clinicopathological characteristics and prognosis of poorly differentiated neuroendocrine carcinoma of the stomach. METHODS: Twenty-three poorly differentiated neuroendocrine carcinomas of the stomach were treated in the Department of Abdominal Surgery at the Cancer Hospital, Fudan University between January 1996 and December 2007. Clinicopathological characteristics and survival data were analyzed. RESULTS: Poorly differentiated neuroendocrine carcinomas of the stomach accounted for 0.52% of all the gastric carcinomas. The tumor occurred more often in males (18 of 23), older patients (mean age of 62 years), upper third of the stomach (16 of 24,one patient had more than one lesion) with large size (mean diameter of 6.8 cm). TNM stages were as follows: stage II in 3 patients, stage III in 12, and stage IIII in 8. Thirteen patients underwent curative resection, while 8 underwent palliative resection and 2 others underwent exploratory laparotomy with biopsy. Of the 21 surgical resection specimens, vascular invasion was found in 18 patients (85.7%), perineural invasion in 16 patients (76.2%), and regional lymph node metastasis in 17 patients (81.0%). Follow up time ranged from 3 to 63 months. Mean overall survival time was 17.7 months. The 1-year, 2-year, and 5-year survival rates were 47.8%, 19.1%, and 4.3%, respectively. Statistically significant differences in survival curves were observed which were related to tumor staging and surgery type, but not related to gender, age, tumor location, or diameter. CONCLUSIONS: Poorly differentiated neuroendocrine carcinomas of the stomach are rare and with poor prognosis. Tumor stage and surgical type have potential impact on survival.

[Synchronous or metachronous primary cancers of other organs in 74 patients with gastric cancer].

OBJECTIVE: To study the incidence, clinicopathological characteristics, diagnosis, treatment, and prognosis of synchronous or metachronous primary cancers in patients with gastric cancer. METHODS: Clinical data of 4426 patients with gastric cancer in our hospital from 1996 to 2007 were reviewed. RESULTS: Seventy-four (1.7%) patients had synchronous or metachronous primary cancer of other organ, of whom 10 were synchronous and 64 were metachronous. Colorectal cancer was the most common type of primary cancer in other organs (43.8%), followed by breast cancer (16.3%). The mean time interval between gastric cancer and metachronous primary cancer was 82.2 (3-354) months. The mean age at the diagnosis of gastric cancer was 61.2 (33-84) years. The 5-year overall survival rate was 42.3%. The 5-year survival rates in patients with synchronous cancer, pre-metachronous cancer or post-metachronous cancer were 15.2%, 42.9% and 51.3%, respectively. Causes of death were primary cancers of other organ in 11 patients, gastric cancer in 24, and renal failure in 1 patient. CONCLUSIONS: Primary cancer of other organ should be considered in the management of gastric cancer. Aggressive treatment should be used for the second primary cancer. Gastric cancer is the main cause of death in these patients.

[Surgical treatment for patients with advanced gastrointestinal stromal tumor after targeted therapy].

OBJECTIVE: To explore the role of surgery and its long-term outcome in patients with advanced gastrointestinal stromal tumor(GIST) treated with imatinib preoperatively. METHODS: Thirteen patients receiving imatinib therapy preoperatively, were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection. RESULTS: Thirteen patients, including 3 patients with locally advanced primary GIST and 10 patients with recurrent or metastatic GIST, underwent surgery after preoperative treatment with imatinib. Complete resections were accomplished in 4 of the 5 responsive disease(RD) patients, and in 1 of the 8 progression disease(PD) patients (38.5%). The progression-free survival(PFS) time for patients with RD and PD were 24.8 months and 2.8 months respectively. The difference of PFS between patients with RD and those with PD was significant(P<0.01). Median overall survival(OS) was not reached in both patients with RD and PD. The difference of OS between patients with RD and those with PD was not significant(P>0.05). CONCLUSION: Surgical intervention following imatinib is feasible and can be considered for patients with advanced GIST responsive to imatinib.

[Clinical analysis of 168 cases of multiple primary colorectal carcinoma].

OBJECTIVE: To study the incidence rate of multiple primary colorectal carcinomas (MPCC) in colorectal carcinoma and to evaluate its clinical and pathological characteristics. METHODS: One hundred and sixty-eight (4.6%) patients from 3663 cases with colorectal carcinoma were diagnosed with MPCC from January 1985 to December 2003. The clinical data of the patients were collected retrospectively to investigate the diagnosis and treatment of MPCC. RESULTS: Of the 168 patients, 81 were diagnosed as synchronous colorectal carcinoma (SC), 72 with metachronous colorectal carcinoma (MC), 15 with both SC and MC. The median age at time of diagnosis of colorectal carcinoma was 58 years old (range from 20 to 82 years old). Three hundred and ninety-three cancer lesions were detected in these 168 cases (mean, 2.3 lesions/case). The rectum and sigmoid colon were the most involved sites (61.6%). Eighteen cases (10.7%) were verified with hereditary non-polyposis colorectal cancer (HNPCC) while another 9 cases were highly suspected. Fourteen patients (8.3%) were found with other malignancies out of large intestine, 41 patients (24.4%) with colorectal adenomas, 72 (42.9%) with adenoma carcinogenesis. Among the 96 SC patients, 91 were given preoperative colonoscopy and 65 (71.4%) got the diagnosis. All the MC patients were diagnosed by postoperative colonoscopy. The overall 5-year survival rate of the 168 patients was 69.8%. CONCLUSIONS: MPCC should be paid more attention in colorectal cancer management. Colonoscopic surveillance is much more important in diagnosis and follow-up of MPCC for reducing the misdiagnosis of SC and detecting more MC in time. Prompt treatment of adenoma can reduce the occurrence of MPCC, and active and standard surgical treatment should be done for MPCC.

[Discussion for clinical treatment in early stage of colorectal carcinoma with the invasion limited in the layer of muscularis mucosae].

OBJECTIVE: To emphasis the importance of recognizing and treating the early colorectal carcinoma with the invasion limited in the layer of muscularis mucosae, and discuss several questions in using the WHO's new diagnostic standards of the prestage of tumors of digestive system. METHODS: A retrospective review was made of 30 patients with invasive carcinoma limited in the layer of muscularis mucosae. All of the patients were treated between July 1986 and July 1999 in Shanghai Cancer Hospital. RESULTS: Among the 30 cases, there were 19 men and 11 women from 20 to 80 years dd (mean, 57.0). The tumor diameter was ranged from 0.8 cm to 8.0 cm (mean, 2.9 cm). 12 patients were given polypectomy while 18 patients were given radical resection. Among the patients given polypectomy, one got recurrence 3 years later, one had the metastasis of lungs 50 months later and had been dead already. Among the patients given radical resection, one had metastasis of lymph nodes peripheral to the tumor, one also had the metastasis of lungs 68 months later but is still alive now, and one had metastasis of lymph nodes in the right upper part of neck 15 months later and then was lost to follow-up. CONCLUSIONS: The patients with early colorectal carcinoma with the invasion limited in the layer of muscularis mucosae could have metastasis of lymph nodes, get local recurrence after polypectomy and even have blood metastasis. Therefore great attention must be paid. Clinicians should be careful to chosen polypectomy. Meanwhile, in order to provide more information of the correct treatment, it will be better if the pathologists could give the original diagnosis at the same time when they use the WHO's new diagnostic standards of the prestage of tumors of digestive system in diagnosing the early invasive carcinoma limited in the layer of muscularis mucosae, for the concept of high-grade intraepithelial neoplasia will be used instead of it, and whether or not it is a really benign tumor, much more clinical research must be done later.