[Analysis of the incidence and symptomatology of low anterior resection syndrome after laparoscopic anterior resection for rectal cancer].

Objective: This study aims to explore the temporal trend of Low Anterior Resection Syndrome (LARS) and its symptoms after laparoscopic anterior resection for rectal cancer. Methods: A retrospective cohort study design was employed. The study included primary rectal (adenocarcinoma) cancer patients who underwent laparoscopic anterior resection at Tongji Hospital, Huazhong University of Science and Technology, between January 1, 2010, and December 31, 2020. Complete medical records and follow-up data at 3, 6, 9, 12, and 18 months postoperatively were available for all patients. A total of 1454 patients were included, of whom 1094 (75.2%) were aged ≤65 years, and 597 (41.1%) were females. Among them, 1040 cases (71.5%) had an anastomosis-to-anus distance of 0-5cm, and 86 cases (5.9%) received neoadjuvant treatment. All patients completed the Chinese version of the LARS questionnaire and their LARS occurrence and specific symptom information were recorded at 3, 6, 9, 12, and 18 months postoperatively. Considering past literature and clinical experience, further subgroup analyses were performed to explore the potential impact factors on severe LARS, including anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma. Results: The occurrence rates of LARS at 3, 6, 9, 12, and 18 months postoperatively were 78.5% (1142/1454), 71.4% (1038/1454), 55.0% (799/1454), 45.7% (664/1454), and 45.7% (664/1454), respectively (χ2=546.180, P<0.001). No statistically significant difference was observed between the 12-month and 18-month time points (P>0.05). When compared with the symptoms at 3 months, the occurrence rates of gas incontinence [1.7% (24/1454) vs. 33.9% (493/1454)], liquid stool incontinence [3.9% (56/1454) vs. 41.9% (609/1454)], increased stool frequency [79.6% (1158/1454) vs. 95.9% (1395/1454)], stool clustering [74.3% (1081/1454) vs. 92.9% (1351/1454)], and stool urgency [46.5% (676/1454) vs. 78.7% (1144/1454)] in the LARS symptom spectrum were significantly alleviated at 12 months (all P<0.05) and remained stable beyond 12 months (all P>0.05). With the extension of postoperative time, the incidence rates of severe LARS exhibited a decreasing trend in different subgroups, of anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma, and reached stability at 12 months postoperatively (all P>0.05). Conclusion: LARS and its specific symptom profile showed a trend of gradual improvement over time up to 1 year postoperatively, and stabilized after more than 1 year. Increased stool frequency and stool clustering are the most common features of abnormal bowel dys function, which improve slowly after surgery.

[Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma].

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Author Correction: Propofol inhibits invasion and enhances paclitaxel-induced apoptosis in ovarian cancer cells through the suppression of the transcription factor slug.

Correction to: European Review for Medical and Pharmacological Sciences 2013; 17 (13): 1722-1729-PMID: 23852894, published online on 15 July 2013. The authors found some mistakes in the article. • The band of ß-actin in Figure 2 was an inadvertent wrong use due to an error in figure preparation. The authors confirm that the correction does not affect the discussion and conclusions of the original article. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/4537.

Eicosapentaenoic acid enhances skeletal muscle hypertrophy without altering the protein anabolic signaling pathway.

This study aimed to examine the effect of eicosapentaenoic acid (EPA) on skeletal muscle hypertrophy induced by muscle overload and the associated intracellular signaling pathways. Male C57BL/6J mice were randomly assigned to oral treatment with either EPA or corn oil for 6 weeks. After 4 weeks of treatment, the gastrocnemius muscle of the right hindlimb was surgically removed to overload the plantaris and soleus muscles for 1 or 2 weeks. We examined the effect of EPA on the signaling pathway associated with protein synthesis using the soleus muscles. According to our analysis of the compensatory muscle growth, EPA administration enhanced hypertrophy of the soleus muscle but not hypertrophy of the plantaris muscle. Nevertheless, EPA administration did not enhance the expression or phosphorylation of Akt, mechanistic target of rapamycin (mTOR), or S6 kinase (S6K) in the soleus muscle. In conclusion, EPA enhances skeletal muscle hypertrophy, which can be independent of changes in the AKT-mTOR-S6K pathway.

[Clinical effect of nutritional and psychological intervention combined with pulmonary rehabilitation exercise on patients with chronic obstructive pulmonary disease].

Objective: To explore the clinical effect of nutritional and psychological intervention combined with pulmonary rehabilitation exercise on patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 260 patients with COPD admitted to the Sixth Affiliated Hospital of Kunming Medical University from October 2014 to October 2017 were included. They were divided into mild, moderate, severe and extremely severe groups according to forced expiratory volume in one second predicted (FEV(1)%prep) of pulmonary function. The patients were divided into control group and comprehensive management group according to the random number table method. The control group was given routine treatment including smoking quitting persuasion, vaccination, oxygen therapy and standardized medication. The comprehensive management group was given additional nutritional support, psychological intervention and pulmonary rehabilitation exercise. The data of the lung function indexes (FEV(1)%prep, FEV(1)/FVC, PaO(2), PaCO(2)), nutritional indexes [body mass index (BMI), albumin (ALB), nutrition risk screening (NRS)2002], anxiety and depression scores, 6-minute walking distance (6MWD), modified medical research council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George's score, and frequency of acute exacerbations were compared between two groups after 12 months of treatment. Results: After 12 months' treatment, PaO(2) in the comprehensive management group was significantly higher than that in the control group [(51.1±7.2) vs (47.0±9.1) mmHg] (1 mmHg=0.133 kPa); Nutritional risk (NRS2002) decreased obviously [(1.1±1.1) vs (2.2±1.0)]; anxiety score [(4.1±2.2) vs (5.6±2.7)]; depression score [(4.1±2.0) vs (5.5±2.6)] and St. George's score [(36.8±20.8) vs (48.6±19.5)] decreased significantly (P<0.05). And the 6MWD was significantly farther [(368.4±72.0) vs (343.4±75.0) m] in management group. The frequency of acute exacerbations was significantly reduced in the mild, moderate and severe groups (P<0.05). But there was no significant difference in FEV(1)%prep, FEV(1)/FVC, PaCO(2), BMI, ALB, mMRC score and CAT score. Conclusion: Nutritional and psychological intervention combined with pulmonary rehabilitation exercise can reduce the nutritional risk and the frequency of acute exacerbations in patients with COPD, relieve anxiety and depression state and improve the quality of life.

[Application of totally extraperitoneal renal autotransplantation with Boari flap-pelvis anastomosis in upper urinary tract urothelial carcinomas treatment].

OBJECTIVE: To evaluate the feasibility and effectiveness of the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis in the treatment of upper urinary tract urothelial carcinoma (UTUC), and to review the experience of renal autotransplantation for UTUC treatment. METHODS: One case of applying the totally extraperitoneal renal autotransplantation with boari flap-pelvis anastomosis to the UTUC treatment was reported, and related literature was reviewed. The patient was a sixty-four-year old man who received right radical nephroureterectomy for right ureteral carcinoma 1 year before and diagnosed as left ureteral carcinoma(G2, high grade) this time. In order to preserve his renal function and avoid the shortness of common kidney-sparing surgery, a totally extraperitoneal procedure, including retroperitoneoscopic nephrectomy, ureterectomy, renal autotransplantation and Boari flap-pelvis anastomosis, was performed to the patient. RESULTS: The operation was completed successfully without perioperative complications. The renal function recovered to preoperative level within 1 week. No deterioration of renal function during the follow-up and no tumor recurrence was observed under cystoscopy at the 3-month postoperative consult. CONCLUSION: The totally extraperitoneal renal autotransplantation with Boari flap-pelvis anastomosis is a feasible and effective treatment for UTUC. The innovative procedure has several advantages compared to the former ones. The extraperitoneal procedure results in significantly less pain, shorter hospital stay, decreased overall time to recovery and lower bowel complications risk without warm ischemia time extension. Meanwhile, the Boari flap-pelvis anastomosis simplifies the follow -up protocols and creates an easy route for cystoscopy and topical therapy. From the systematic clinical analysis, as well as the related literature review, it's been concluded that the renal autotransplantation can be a reasonable option for the patients who have UTUC in solitary kidney or have bilateral UTUC. This type of treatment possesses advantages of preservation of renal function and total resection of malignant lesions. But long-term data and large cohort study on renal function or tumor recurrence are still absent which will be necessary to confirm the advantages of this approach.

Correction: Exosomal Wnt-induced dedifferentiation of colorectal cancer cells contributes to chemotherapy resistance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Exosomal Wnt-induced dedifferentiation of colorectal cancer cells contributes to chemotherapy resistance.

Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.

Adipose insulin resistance is associated with cardiovascular risk factors in polycystic ovary syndrome.

PURPOSE: The effects of adipose insulin resistance on cardiovascular risk factors in polycystic ovary syndrome (PCOS) remain largely unknown. We aimed to investigate associations between adipose insulin resistance and cardiovascular risk factors in PCOS. METHODS: A total of 207 PCOS and 47 non-PCOS women were recruited from a large reproductive medicine center in this cross-sectional study. The PCOS diagnosis was based on the Rotterdam Criteria. The subjects received a standard oral glucose tolerance test. Adipose insulin resistance was evaluated using a validated index (adipose-IR = fasting insulin × free fatty acid concentrations). RESULTS: The women with PCOS showed a higher adipose-IR index, and the adipose-IR index was tightly associated with the blood pressure, glucose and lipid parameters. A total of 98.0% of the women with PCOS in the highest adipose-IR quartile showed cardiovascular risk factors (obesity, hypertension, glucose intolerance or dyslipidemia), and this percentage was significantly higher than the percentage of those in the lowest quartile (32.7%). In addition, the percentages of women with three (31.4%) and four (13.7%) cardiovascular risk factors were significantly elevated in the highest adipose-IR quartile. The multivariable logistic regression analysis indicated that each 1-SD increment in the adipose-IR index resulted in higher risks of obesity (OR = 3.18, 95% CI = 2.12-4.76), hypertension (OR = 1.89, 95% CI = 1.31-2.73), glucose intolerance (OR = 2.45, 95% CI = 1.73-3.48), and dyslipidemia (OR = 2.18, 95% CI = 1.57-3.01). The C-reactive protein (CRP) level was positively associated with the adipose-IR index in women with PCOS (r = 0.45, P < 0.001). CONCLUSIONS: The adipose-IR index was associated with cardiovascular risk factors in women with PCOS. Chronic inflammation may induce insulin resistance in the adipose tissue of women with PCOS.

[The influence of molecular classification of breast cancer on the safety of breast-conserving surgery].

Objective: To analyze the relationship between the breast cancer molecular classification and the prognosis of patients underwent breast-conserving therapy and to discuss the safety of the breast conserving surgery from the choice of operation in terms of breast cancer molecular classification. Methods: Clinical data of 618 patients with breast-conserving therapy in Tianjin Medical University Cancer Institute and Hospital from August 2005 to August 2010 were analyzed retrospectively. According to the molecular classification when breast cancer was diagnosed, patients were subdivided into five groups, including Luminal A, Luminal B1, Luminal B2, HER-2-positive and Triple-negative. Clinicopathological characteristics and prognosis were compared among five groups and the influencing factors of local recurrence, distant metastasis and overall survival were analyzed. Results: Among 618 patients, there were 148 cases Luminal A, 231 cases Luminal B1, 63 cases Luminal B2, 40 cases HER-2-positive and 136 cases Triple-negative. The age, family history, TNM stage, calcification, histological grade, pathological type and response to endocrine therapy of these 5 molecular types of breast cancer patients were significantly different (all P<0.05). The 5-year local regional recurrence-free survival rates of Luminal A, Luminal B1, Luminal B2, HER-2-positive and Triple-negative were 99.3%, 98.7%, 98.4%, 94.9% and 95.9%, respectively, without significant differences (P=0.104). The 5-year distant metastasis-free survival rates of these 5 types were 97.3%, 95.7%, 93.7%, 87.5% and 91.4%, respectively, with significant differences (P=0.013). Moreover, the 5-year overall survival rates of these 5 types were 98.6%, 97.8%, 98.4%, 92.5% and 95.6%, respectively, without significant differences (P=0.153). Multifactor analysis showed that radiotherapy (HR=0.036, P=0.049) and the number of lymph node metastases (HR=10.72, P=0.004) were independent factors of local recurrence of breast cancer patients underwent breast-conserving therapy. The age (HR=0.369, P=0.046), status of surgical margin (HR=5.486, P=0.007), number of lymph node metastases (HR=2.882, P=0.023) and molecular typing (HR=5.191, P=0.008) were independent factors of distant metastasis of above breast cancer patients. None of the factors were found to be independent factors of the overall survival of these breast cancer patients. Conclusions: Breast conserving therapy does not increase the risks of local recurrence and death of HER-2-positive and Triple-negative breast cancer patients. Therefore, breast conserving therapy can be accepted by patients with HER-2-positive and Triple-negative breast cancer.

A 4-miRNAs signature predicts survival in glioblastoma multiforme patients.

BACKGROUND: Although O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status is an important marker for glioblastoma multiforme (GBM), there is considerable variability in the clinical outcome of patients with similar methylation profles. OBJECTIVE: We examined whether a MicroRNA (miRNA) signature can be identified for predicting clinical outcomes and helping in treatment decisions. METHODS: The differentially expressed miRNAs were evaluated in 6 pairs of short- (⩽ 450 days) and long-term survivors (> 450 days) by using microarray. Real time quantitative PCR (qRT-PCR) was applied to further verify screened miRNAs with a greater number of samples (n= 48). Meanwhile, functional interpretation of miRNA profile was carried out based on miRNA-target databases. In addition, MGMT promoter methylation status was tested by means of pyrosequencing (PSQ) testing. RESULTS: Six miRNAs were upregulated in the long-term survival group (fold change ⩾ 2.0, P< 0.05). The further verification by qRT-PCR indicated that the increase in let-7g-5p, miR-139-5p, miR-17-5p and miR-9-3p level in long-term survivors was statistically significant. Kaplan-Meier survival analysis showed that high expression of a prognostic 4-miRNA signature was significantly associated with good patient survival (p= 0.0012). The signature regulated signaling pathways including Calcium, MAPK, ErbB, mTOR and cell cycle involved in carcinogenesis from glial progenitor cell to primary GBM. CONCLUSIONS: The 4-miRNA signature was identified as an independent prognostic biomarker that identified patients who have a favorable outcome.

Immunohistochemical localization of sex hormone receptors in two Raillietina tapeworms.

Sex hormone receptors play critical roles in development and reproduction. However, it is not known whether they exist in Raillietina tapeworms, and if they do, whether they have a similar function to that in vertebrates. We examined the immunohistochemical distributions of androgen receptors (ARs), estrogen receptors (ERs), and progesterone receptors (PRs) in the tissues of two tapeworm species: Raillietina echinobothrida and Raillietina tetragona. Immunopositive ARs were found in the entire reproductive system of R. echinobothrida, including the testes, ovaries, and oocysts, and weakly immunopositive ERs and PRs were found in the testes, ovaries, and oocysts. Immunopositive ARs were also found throughout the entire reproductive system of R. tetragona, including the testes, ovaries, and oocysts, and weakly immunopositive ERs were in the testes and oocysts; the PRs were distributed in an immunonegative manner. The results show that androgens and their receptors play critical roles in reproductive system development in the two tapeworms. The immunoreactivity and tissue localizations of the sex hormone receptors suggest that, in both species, they have similar functions as in vertebrates, and modulate reproduction.

[Correlation between polymorphism of angiotensin-converting enzyme gene and the lower extremity atherosclerosis in type 2 diabetes mellitus patients].

Objective: To explore the correlation between polymorphism of the angiotensin-converting enzyme (ACE) gene and lower extremity atherosclerosis (LEA) in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 380 patients diagnosed with T2DM in Department of Endocrinology from June 2015 to March 2016 were enrolled and divided into two groups: group A had no LEA (n=120) and group B had LEA(n=260). Color doppler ultrasound was used to detect the vascular lesions of the patients. For all patients in groups A and B, the polymerase chain reaction (PCR) was applied to determined the insertion/deletion polymorphism in intron 16 of the ACE gene of the patients. Then the blood pressure, blood lipid, glycated hemoglobin, and renal function were measured. Furthermore, the measured data was compared between the two groups. Multivariate logistic regression analysis was used to analyze the independent risk factors for LEA. Results: There was no significant statistical difference in age, sex, smoking and disease course between the two groups. The frequencies of DD genotype and D allele in the ACE gene of group B were much higher than those in group A. More specifically, DD genotype frequency was 18.8% in group B and 9.2% in group A, D allele frequency was 36.8% in group B and 29.2% in group A (all P<0.05). Multivariate logistic regression analysis showed that DD genotype in ACE gene (OR=2.744, 95% CI: 1.326-5.682), systolic blood pressure (OR=1.725, 95% CI: 1.072-2.778), total cholesterol (OR=3.785, 95% CI: 1.796-7.978), and glycated hemoglobin (OR=2.612, 95% CI: 1.602-4.258) were risk factors for LEA in T2DM patients. Conclusions: ACE gene insertion/deletion polymorphism was associated with the incidence of LEA in T2DM patients. DD genotype of the ACE gene may be a genetic risk factor for T2DM patients with concurrent atherosclerosis.

[Impact of immediate breast reconstruction on the onset of adjuvant chemotherapy and on the postoperative complications].

Objective: To explore the impact of immediate breast reconstruction on the onset of adjuvant chemotherapy and on the postoperative complications. Methods: We retrospectively analyzed the clinical data from female breast cancer patients treated by either modified radical mastectomy with immediate breast reconstruction(IBR) ( n=108) or modified radical mastectomy alone(n=115), followed by adjuvant chemotherapy at our department between January 2011 and December 2012. Results: There was no significant difference in the overall complication rates between the IBR group and modified radical mastectomy group (49.1% vs. 52.2%, P=0.87). However, more secondary surgery was applied in the IBR group than the modified radical mastectomy group (13.0% vs. 1.7%, P=0.001). However, the incidence of hematoma in the modified radical mastectomy group was significantly higher than the IBR group (17.4% vs. 4.6%, P=0.003). There was a significant difference in the onset of adjuvant chemotherapy between the IBR group and modified radical mastectomy group (21 days vs. 11days, P<0.001). Conclusions: Immediate breast reconstruction has no significant impact on the overall complication rate, but increases the incidence of secondary surgery, especially after the initiation of chemotherapy. In addition, it slightly delays adjuvant chemotherapy in the patients.

Effects of cartilage-derived morphogenetic protein 1 (CDMP1) transgenic mesenchymal stem cell sheets in repairing rabbit cartilage defects.

The aim of this study was to investigate the abilities of cartilage-derived morphogenetic protein 1 (CDMP1) transgenic cell sheets in repairing rabbit cartilage defects. Rabbit CDMP1 transgenic bone marrow mesenchymal stem cell (BMSC) sheets (CDMP1-BMSCs) were cultured on temperature-sensitive culture dishes, and CDMP1 expression and type II collagen protein in the cell sheets were detected. Tissue-engineered cell sheets were constructed and transplanted into defect rabbit thyroid cartilage, to investigate the expression of engineered cartilage collagen protein and proteoglycan (GAG). The experiment was divided into three groups; A) BMSC sheet, B) Ad-CMV-eGFP-transfected cell sheet, and C) Ad-CMV-hCDMP1-IRES-eGFP-transfected cell sheet. The expression of CDMP1 was detected in the transgenic cell sheets. The engineered cartilage exhibited positive immunohistochemical and Alcian blue staining. The expression levels of type II collagen protein and GAG in group A were positive, whereas those in group B and group C were negative (P < 0.05). The CDMP1-BMSC sheets had a good cartilage differentiation activity, and could effectively repair rabbit laryngeal cartilage defects.

Phoenixin-14 enhances memory and mitigates memory impairment induced by Aß1-42 and scopolamine in mice.

Phoenixin (PNX) is a recently discovered neuropeptide shown to be involved in regulating the reproductive system, anxiety-related behaviors and pain though its receptor is still unknown. PNX-14, one of the endogenous active isoforms, is reported to regulate gonadotropin releasing hormone (GnRH) receptor expression and GnRH secretion. Because GnRH system is thought to be involved in the regulation of learning and memory processes, we hypothesized that PNX-14 might be mediate learning and memory. Here, we investigated the effects of PNX-14 in memory processes, using novel object recognition (NOR) and object location recognition (OLR) tasks. Our results revealed that intracerebroventricular (i.c.v.) injection of PNX-14 (25nmol) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-enhancing effects of PNX-14 were also seen when it was infused into the hippocampus. Moreover, these memory-improving effects of PNX-14 could be blocked by a GnRH receptor antagonist (Cetrorelix). The memory-improving effects of PNX-14 were not related to any effects on locomotor activity. Additionally, the results suggested that i.c.v. injection of PNX-14 mitigate the memory impairment induced by the amyloid-ß1-42 (Aß1-42) peptide and scopolamine. The present results indicate that PNX-14 facilitates memory formation and prolongs memory retention through activation of the GnRH receptor, and mitigates the memory-impairing effects of Aß1-42 and scopolamine, suggesting that PNX-14 may be effective as a drug for enhancing memory and treating Alzheimer׳s disease.

Protection against cognitive impairment and modification of epileptogenesis with curcumin in a post-status epilepticus model of temporal lobe epilepsy.

Epileptogenesis is a dynamic process initiated by insults to the brain that is characterized by progressive functional and structural alterations in certain cerebral regions, leading to the appearance of spontaneous recurrent seizures. Within the duration of the trauma to the brain and the appearance of spontaneous recurrent seizures, there is typically a latent period, which may offer a therapeutic window for preventing the emergence of epilepsy. Previous animal studies have shown that curcumin can attenuate acute seizure severity and brain oxidative stress, but the effect of curcumin on epileptogenesis has not been studied. We examined the effect of continued administration of curcumin during the latent period on epileptogenesis and the deleterious consequences of status epilepticus in adult rats in a post-status epilepticus model of temporal lobe epilepsy induced by kainic acid. We demonstrate that, while administration of curcumin treatment during the latent period does not prevent occurrence of spontaneous recurrent seizures after status epilepticus, it can attenuate the severity of spontaneous recurrent seizures and protect against cognitive impairment. Thus, treatment with curcumin during the latent period following status epilepticus is beneficial in modifying epileptogenesis.

LY2109761 inhibits metastasis and enhances chemosensitivity in osteosarcoma MG-63 cells.

OBJECTIVE: Studies have shown that transforming growth factor-beta (TGF-ß) is associated with metastasis and chemoresistance of osteosarcoma. The TGF-ß kinase inhibitor LY2109761 could inhibits metastasis and enhances chemosensitivity in several cancers, but its role and mechanisms in osteosarcoma (OS) is unclear. Here, we investigated the role and mechanism of LY2109761 on metastasis and chemosensitivity of OS MG-63 cells. MATERIALS AND METHODS: MG-63 cells were treated with LY2109761 or/and cisplatin. The cell viability and apoptosis of MG-63 cells were detected by MTT and ELISA. Matrigel invasion assay was used to detect cell invasion in vitro. pSMAD2 and S100A4 was detected by western blot assay. Furthermore, the efficacy of LY2109761 combined with S100A4 cDNA plaismid transfection on cell viability, apoptosis and chemosensitivity to cisplatin in OS MG-63 cells was further examined. RESULTS: LY2109761 was sufficient to induce apoptosis and inhibited growth of MG-63 cells in vitro. Combination with LY2109761 significantly augmented the cytotoxicity of cisplatin in MG-63 cells. LY2109761 significantly inhibited invasion of MG-63 cells in vitro. The LY2109761-induced increase in cell apoptosis and the cytotoxicity of cisplatin, and decrease in cell invasion was blocked completely when S100A4 expression was restored in the MG-63 cells by S100A4 cDNA plasmid transfection. CONCLUSIONS: Our data indicate that LY2109761 suppresses OS metastasis and enhanced chemosensitivity by targeting S100A4. LY2109761 may have important implications for the development of strategies for inhibiting metastasis and overcoming OS cell resistance to chemotherapy.