The Harbinger transposon-derived gene PANDA epigenetically coordinates panicle number and grain size in rice.

Transposons significantly contribute to genome fractions in many plants. Although numerous transposon-related mutations have been identified, the evidence regarding transposon-derived genes regulating crop yield and other agronomic traits is very limited. In this study, we characterized a rice Harbinger transposon-derived gene called PANICLE NUMBER AND GRAIN SIZE (PANDA), which epigenetically coordinates panicle number and grain size. Mutation of PANDA caused reduced panicle number but increased grain size in rice, while transgenic plants overexpressing this gene showed the opposite phenotypic change. The PANDA-encoding protein can bind to the core polycomb repressive complex 2 (PRC2) components OsMSI1 and OsFIE2, and regulates the deposition of H3K27me3 in the target genes, thereby epigenetically repressing their expression. Among the target genes, both OsMADS55 and OsEMF1 were negative regulators of panicle number but positive regulators of grain size, partly explaining the involvement of PANDA in balancing panicle number and grain size. Moreover, moderate overexpression of PANDA driven by its own promoter in the indica rice cultivar can increase grain yield. Thus, our findings present a novel insight into the epigenetic control of rice yield traits by a Harbinger transposon-derived gene and provide its potential application for rice yield improvement.

The CTIP-mediated repair of TNF-α-induced DNA double-strand break was impaired by miR-130b in cervical cancer cell.

Chemotherapeutic drugs that induce DNA damage have the potential to kill cancer cells, but DNA repair protects cells from damage-induced cell death. Thus, eliminating DNA repair is a potential approach to overcome cell drug resistance. In this study, we observed that the gene expression of C-terminal binding protein interacting protein (CTIP) was promoted by TNF-α stimulation and prevented TNF-α-induced double-strand breaks (DSBs) in the genomes of cervical cancer cells. The putative miR-130b targeted site within 3' untranslated region (UTR) of CTIP mRNA was identified through in silico analysis and confirmed based on experimental data. By targeting the CTIP gene, miR-130b caused the accumulation of DSBs and accelerated cell apoptosis in combination with poly ADP ribose polymerase (PARP) inhibitors. Additionally, overexpression of the CTIP gene elevated cancer cell viability by promoting proliferation while miR-130b antagonized CTIP-stimulated cell reproduction. Consequently, miR-130b destruction of DNA repair should be employed as a strategy to treat cervical cancer. SIGNIFICANCE OF THE STUDY: Cervical cancer threatens the health of women all over the world. In this study, we observed that miR-130b was able to cause the accumulation of DNA double-strand breaks through suppressing the gene expression of C-terminal binding protein interacting protein and to accelerate cell apoptosis by preventing DNA damage repairs in cervical cancer cells. As far as we know, the impact of miR-130b on the DNA double-strand break repair and on the cell apoptosis induced by the destruction of DNA repair in cervical cancer cells was firstly documented. It is reasonable to believe that miR-130b destruction of DNA repair may be employed as a strategy to treat cervical cancer in the future.

Efficacy and safety of endoscopic submucosal dissection in treating gastric subepithelial tumors originating in the muscularis propria layer: a single-center study of 144 cases.

OBJECTIVE. Subepithelial tumors (SETs) in the stomach are usually considered benign. However, some do have potential for malignant transformation, especially when originating in the muscularis propria (MP). Our study aimed to evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for gastric SETs originating in MP. MATERIAL AND METHODS. A total of 145 gastric MP SETs in 144 patients were treated by ESD between September 2008 and December 2012. Characteristics of patients and SETs, therapeutic outcomes, pathologic characteristics, complications and follow-up outcomes were evaluated. RESULTS. Among the 144 patients, 104 were female (72.22%) and 40 were male (27.78%), and the mean age was 55.75 ± 11.29 years (range 18-78 years). The mean size of the tumors determined by endoscopic ultrasound (EUS) was 15.14 ± 9.70 mm (range 3-50 mm). En bloc complete resection was achieved in 134 of 145 tumors, giving a complete resection rate of 92.41%. The final histopathologic diagnoses included 52 leiomyomas, 89 gastrointestinal stromal tumors, 3 neurogenic tumors and 1 lipoma. Perforations occurred in 21 patients (14.48%) and were endoscopically repaired with clips or nylon bands. Intraoperative bleeding occurred in seven patients (4.83%) and was corrected with argon plasma coagulation (APC) or hot biopsy forceps. No local recurrence or distant metastasis was detected during a mean follow-up of 19.14 ± 10.29 months (range 3-51 months). CONCLUSIONS. ESD appears to be an effective and safe treatment for gastric SETs originating in MP.

Endoscopic submucosal dissection of large gastrointestinal stromal tumors in the esophagus and stomach.

BACKGROUND AND AIM: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract with potential for malignant transformation, are mainly treated by open surgery or laparoscopic resection. The aim of this retrospective study was to evaluate the clinical efficacy, safety, and feasibility of endoscopic submucosal dissection (ESD) for large-size (2-5 cm) GISTs in the esophagus and stomach. METHODS: A total of 31 patients with large-size GISTs in the esophagus (6 patients) and stomach (25 patients) underwent ESD between September 2008 and December 2011. Demographics, clinical data, therapeutic outcomes, complications, pathological characteristics, risk classification, and follow-up outcomes were recorded. RESULTS: ESD was successfully performed in 31 patients at age of 59.06 ± 7.23 years (range: 46-74). The mean time of the procedure was 70.16 ± 16.25 min (range: 40-105). Perforation for 2-10 mm occurred in six patients (19.35%) and was endoscopically repaired with clips or nylon bands, with no conversions to open surgery. Intraoperative bleeding occurred in three patients (9.68%) and was corrected with argon plasma coagulation or hot biopsy forceps. No mortalities occurred. The mean size of the resected tumors was 2.70 ± 0.72 cm (range: 2.0-5.0). Out of the 31 patients, 24 (77.42%) were at very low risk and 7 (22.58%) were at low risk. Positive rate of CD117, DOG-1, and CD34 were 83.87%, 12.90%, and 100%, respectively. A follow up for 14.29 ± 8.99 months (range: 3-39) showed no recurrence or metastasis. CONCLUSIONS: ESD appears to be an effective, safe, and feasible treatment for large-size GISTs in the esophagus and stomach.

Exploration of the Function of Ginsenoside RD Attenuates Lipopolysaccharide-Induced Lung Injury: A Study of Network Pharmacology and Experimental Validation.

OBJECTIVE: Ginsenoside Rd (GSRd) displays a variety of pharmacological effects. However, the underlying role in acute lung injury (ALI) is not clear. In this study, the protective effect of GSRd on lipopolysaccharide (LPS)-induced ALI is investigated to explore the potential mechanisms. METHODS: GSRd-target-ALI-related gene set was constructed. And bioinformatics tools were used to discover the potential mechanism. We observed the survival of subjects for 72 h. In addition, male BALB/c mice were intraperitoneal injected with GSRd (25 and 50 mg/kg) after received one intratracheal instillation of LPS. Inflammatory changes, oxidative stress, and phosphorylation were assessed to study the biological effects. RESULTS: A total of 245 interaction genes were collected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were enriched in immune-inflammatory system. Among them, PI3K-Akt signaling pathway was the highest-ranked pathway of inflammatory response. In vivo study, it was found that GSRd improved survival in endotoxemic mice and inhibited the major characteristic of ALI. And the p-PI3K and p-Akt expression was significantly decreased by GSRd treatment. CONCLUSION: GSRd could protect mice against LPS-induced ALI effectively by inhibiting the PI3K-Akt signaling pathway.

Clinical presentations of gastric small gastrointestinal stromal tumors mimics functional dyspepsia symptoms.

AIM: To explore whether clinical presentations of gastric small gastrointestinal tumors (GISTs) mimics gastrointestinal dyspepsia symptoms. METHODS: The endosonographic data of 167 patients who underwent endoscopic submucosal dissection at the Tianjin Medical University General Hospital, China between 2009 and 2011 were analyzed. GISTs and leiomyomas had a similar intragastric distribution and similar locations within the gastric wall. Therefore, patients with GISTs were chosen as the study group and those with leiomyomas were chosen as the control group. Dyspepsia symptom questionnaires were used to investigate and compare the gastrointestinal symptoms of patients with GISTs and those with gastric leiomyomas before and after endoscopic submucosal dissection (ESD). The questionnaires evaluated symptoms such as epigastric pain, heartburn, regurgitation, epigastric discomfort, nausea and vomiting, abdominal bloating, and eructation. Symptoms were assessed using a four-point scoring scale. RESULTS: GISTs were the most common gastric submucosal lesion (67 cases, 40.12%), followed by leiomyomas (38 cases, 22.75%). Both groups were similar in terms of gender distribution (P = 0.49), intragastric location (P = 0.525), and originating layer within the gastric wall (P = 0.449), but leiomyomas were more commonly found in the proximal fundus (P < 0.05). Overall, 94.2% of the patients with small GISTs and 93.5% of those with gastric leiomyomas experienced some dyspepsia; however, total symptom scores were significantly lower in the GIST group than in the leiomyoma group (1.34 ± 1.27 vs 2.20 ± 1.70, P < 0.05). Each component of the symptom score demonstrated a statistically significant improvement in the GIST patients after ESD (P < 0.05), including epigastric pain (0.80 ± 0.90 vs 0.13 ± 0.46), heartburn (0.63 ± 1.08 vs 0.13 ± 0.41), regurgitation (0.55 ± 0.87 vs 0.22 ± 0.57), epigastric discomfort (0.70 ± 0.98 vs 0.32 ± 0.47), nausea and vomiting (0.27 ± 0.62 vs 0.05 ± 0.21), abdominal bloating (0.70 ± 0.90 vs 0.27 ± 0.49), and eructation (0.36 ± 0.61 vs 0.21 ± 0.46). For leiomyoma patients, symptoms such as heartburn, nausea, vomiting, and eructation improved after treatment; however, these improvements were not statistically significant (P > 0.05). Thus, the pathophysiology of dyspepsia symptoms may be different between the two groups. CONCLUSION: Symptoms of gastric small GISTs may mimic those of functional dyspepsia. An alternative diagnosis should be considered in patients with functional dyspepsia and treatment failure.

Endoscopic submucosal dissection for gastrointestinal mesenchymal tumors adjacent to the esophagogastric junction: we need to do more.

OBJECTIVE: Extensive surgery is the mainstay of therapy for patients with gastrointestinal mesenchymal tumors (GIMTs) adjacent to the esophagogastric junction (EGJ). However, this modality is invasive and may interfere with anatomic consistency of the digestive tract. Therefore, we evaluated the feasibility, safety, and efficacy of endoscopic submucosal dissection (ESD) for GIMTs close to the EGJ and factors related to incomplete resection. PATIENTS AND METHODS: For 39 GIMTs adjacent to the EGJ in 39 consecutive patients, the baseline information, complications, and therapeutic outcomes were recorded. Subsequently, risk factors, focusing on age, sex, tumor size, extent, shape, perforation presence/absence, and histopathology, were analyzed. RESULTS: Complete removal of junctional GIMTs was achieved in 32 cases, giving an overall complete resection rate of 82%. The mean tumor size was 16.1±12.7 (median, 12; range, 4-50) mm. There were no major intra- and postoperative complications, but two small perforations were found. The final histopathologic diagnoses included 28 leiomyomas, 10 gastrointestinal stromal tumors, and 1 schwannoma. No local recurrence or distant metastasis was observed during a mean follow-up of 15.7±8.4 (median, 16; range, 6-35) months. Univariate analysis showed incomplete resection was associated with tumor shape and size. Multivariate regression analysis identified tumor irregularity (odds ratio=37.50, 95% confidence interval=4.253-330.627) as the single factor associated with incomplete resection. CONCLUSIONS: ESD is feasible and safe for well-selected patients with GIMTs adjacent to the EGJ. Irregular tumor shape should be considered as a technical difficulty while performing ESD. Oncologic outcomes need to be assessed with longer follow-up.