Protective effect of trans-nerolidol on vascular endothelial cell injury induced by lipopolysaccharides / Efectos protectores del trans-nerolidol en lesiones inducidas por lipopolisacáridos en células endoteliales vasculares

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner

Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway.

BACKGROUND: CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors, including gastric cancer (GC), and is associated with tumor progression and immune infiltration; however, the roles and mechanisms of CALD1 in epithelial-mesenchymal transition (EMT) in GC are unknown. AIM: To investigate the role and mechanism of CALD1 in GC progression, invasion, and migration. METHODS: In this study, the relationship between CALD1 and GC, as well as the possible network regulatory mechanisms of CALD1, was investigated by bioinformatics and validated by experiments. CALD1-siRNA was synthesized and used to transfect GC cells. Cell activity was measured using the CCK-8 method, cell migration and invasive ability were measured using wound healing assay and Transwell assay, and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot. A GC cell xenograft model was established to verify the results of in vitro experiments. RESULTS: Bioinformatics results showed that CALD1 was highly expressed in GC tissues, and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC. The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression, and a prognostic model was constructed and evaluated. The experimental results were consistent with the results of the bioinformatics analysis. The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1, with the strongest expression found in AGS and MKN45 cells. Cell activity was significantly reduced after CALD1-siRNA transfection of AGS and MKN45 cells. The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection, and the related mRNA and protein expression was altered. According to bioinformatics findings in GC samples, the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway, and was closely related to the PI3K-Akt signaling pathway. Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K, p-AKT, and p-mTOR, members of the PI3K-Akt pathway,while decreasing the expression of PTEN; PI3K-Akt inhibitor treatment decreased the expression of PI3K, p-AKT, and p-mTOR in cells overexpressing CALD1 (still higher than that in the normal group), but increased the expression of PTEN (still lower than that in the normal group). CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor. Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor. The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1, whereas the effect of overexpression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor. Animal experiments showed that tumour growth was slow after inhibition of CALD1, and the expression of some PI3K-Akt and EMT pathway proteins was altered. CONCLUSION: Increased expression of CALD1 is a key factor in the progression, invasion, and metastasis of GC, which may be associated with regulating the PI3K-Akt pathway to promote EMT.

New treatment for gastric duplication cyst: Endoscopic ultrasonography-guided fine-needle aspiration combined with lauromacrogol sclerotherapy: A case report.

BACKGROUND: Gastric duplication cysts are very rare disease that are mainly diagnosed by endoscopic ultrasonographic fine-needle aspiration biopsy. In the past, this disease was usually treated with traditional surgery and rarely with minimally invasive endoscopic surgery. However, minimally invasive endoscopic therapy has many advantages, such as no skin wound, organ preservation, postoperative pain reduction, early food intake, fewer postoperative complications, and shorter post-procedure hospitalization. CASE SUMMARY: We report a case of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) combined with lauromacrogol sclerotherapy for pyloric obstruction due to gastric duplication cysts. CONCLUSION: EUS-FNA combined with lauromacrogol sclerotherapy provides a new option for the treatment of gastrointestinal duplication cysts.

Neoadjuvant docetaxel, oxaliplatin plus capecitabine versus oxaliplatin plus capecitabine for patients with locally advanced gastric adenocarcinoma: long-term results of a phase III randomized controlled trial.

BACKGROUND: Neoadjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine (DOX regimen) is rarely used in Eastern countries and its efficacy and safety in advanced gastric cancer have not been reported. In this open-label, randomized, controlled trial, the authors aimed to assess the clinical efficacy of neoadjuvant chemotherapy using the DOX and oxaliplatin plus capecitabine (XELOX) regimens, in comparison to surgery alone. MATERIALS AND METHODS: Three hundred patients younger than 60 years with potentially resectable advanced gastric cancer (cT3-4, Nany, M0) were enrolled in this randomized controlled clinical trial between November 2014 and June 2018. The primary endpoint of the study was the pathological complete response (pCR) rate. Secondary endpoints included 3-year overall survival (OS), 3-year disease-free survival. RESULTS: In total, 280 patients (93 in the DOX group, 92 in the XELOX group, and 95 in the surgery group) were included in the per-protocol analysis. The DOX group demonstrated a significantly higher pCR rate compared to the XELOX group (16.1 vs. 4.3%, P =0.008). For patients with intestinal type, the DOX group exhibited significantly higher rates of both pCR and major pathological response compared to the XELOX group ( P =0.007, P <0.001). The 3-year OS rates of the DOX group, the XELOX group and the surgery group were 56.9, 44.6, and 34.7%, respectively. The 3-year disease-free survival rates were 45.2, 40.2, and 28.4%, respectively. The neoadjuvant DOX regimen demonstrated a significant improvement in the 3-year OS of patients compared to the neoadjuvant XELOX regimen ( P =0.037). CONCLUSION: The neoadjuvant DOX regimen has shown the potential to increase the pCR rate and improve the prognosis of patients with advanced gastric cancer who are under 60 years old.

Development of protective agents against ovarian injury caused by chemotherapeutic drugs.

BACKGROUND: Chemotherapy is one of the causes of ovarian injury and infertility. Although assisted reproductive technology helps young female patients with cancer become pregnant, preventing chemotherapy-induced ovarian injury will often possess even more significant benefits. OBJECTIVE: We aimed at demonstrating the hazardous effects and mechanisms of ovarian injury by chemotherapeutic agents, as well as demonstrating agents that protect the ovary from chemotherapy-induced injury. RESULTS: Chemotherapeutic agents cause death or accelerate activation of follicles and damage to the blood vessels in the ovary, resulting in inflammation. These often require drug development to protect the ovaries from injury. CONCLUSIONS: Our findings provide a basis for the development of drugs to protect the ovaries from injury. Although there are many preclinical studies on potential protective drugs, there is still an urgent need for a large number of clinical experiments to verify their potential use.

Wnt signaling in triple-negative breast cancers: Its roles in molecular subtyping and cancer cell stemness and its crosstalk with non-coding RNAs.

Triple-negative breast cancers (TNBCs) are now acknowledged as a collection of diseases encompassing distinct histological plasticity, multi-tier molecular heterogeneity, as well as different outcomes. Despite decades of efforts, the molecular subtyping strategy has been theoretical, and target therapies based on molecular alternations barely improve survival rates of TNBC patients, and thus traditional chemotherapy remains the standard of care in clinic. The Wnt signaling is an evolutionarily conserved signaling pathway, playing critical roles in embryogenesis and neoplastic disease. The dysregulation of Wnt signaling pathway endows cancer cells with stem cell-like capacities of self-renewal, cell proliferation and differentiation, thus exerting crucial roles in tumorigenesis and therapy responses. Recently, the gene expression assays and genomic sequencing have demonstrated that the dysregulation of Wnt signaling is associated with progression of TNBCs, particularly with metastasis, relapse and therapy resistance. In this review, we highlight the dysregulation of Wnt signaling in TNBCs and its potential biological roles in molecular subtyping and stemness traits of specific subtypes, as well as its crosstalk with ncRNAs in regulation of the biological features of TNBCs, aiming to update this important oncogenic signaling pathway in TNBCs.

Assessment of Carbon Nanoparticle Suspension Lymphography-Guided Distal Gastrectomy for Gastric Cancer.

Importance: Carbon nanoparticle suspension injection (CNSI) can be used to visualize lymph node (LN) drainage in gastric cancer. The tracing and diagnostic value of carbon nanoparticle suspension lymphography-guided distal gastrectomy for gastric cancer has not been thoroughly reported. Objective: To compare the number of lymph nodes identified in patients with gastric cancer receiving a CNSI vs no injection. Design, Setting, and Participants: This is a retrospective cohort study including patients with clinical T1 to T4 disease who underwent laparoscopic or robotic distal gastrectomy. Data from a cohort of 1225 patients at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China) from November 2019 to February 2021 were analyzed. Patients were divided into the CNSI group and conventional group after 1:1 propensity matching analysis. The mean number of LNs detected was compared between groups, and the diagnostic role of CNSI was analyzed in the CNSI group. Statistical analysis was performed from May to July 2021. Exposure: CNSI was peritumorally injected under an endoscope 1 day before surgery in the CNSI group, and the conventional group did not receive any treatment before surgery. Main Outcomes and Measures: The main outcome was the number of LNs detected. Gastrectomy with systematic D1+ (ie, stations 1, 3, 4sb, 4d, 5, 6, and 7) or D2 (ie, all D1 stations, plus 8a, 9, 11p, and 12a) lymphadenectomy was performed. Black-stained LNs and nonblack-stained LNs were examined separately in the CNSI group. Results: A total of 312 consecutive patients (mean [SD] age, 56.7 [10.4] years; 216 [69.2%] men) who underwent distal gastrectomy were enrolled, including 78 patients in the CNSI group, and another 78 patients determined from 1:1 propensity score matching, making an overall cohort size of 156 patients. The mean (SD) number of LNs detected in the CNSI group was 59.6 (21.4), which was significantly higher than that in the conventional group (30.0 [11.3] LNs; P < .001). In the CNSI group, the mean (SD) number of LNs detected at black-stained LN stations was significantly higher than that at nonstained LN stations (9.2 [6.1] LNs per station vs 3.5 [3.2] LNs per station; P < .001). For black-stained LN stations, the sensitivity was 97.8% (95% CI, 91.6%-99.6%), specificity was 38.1% (95% CI, 34.2%-42.3%), positive predictive value was 20.1% (95% CI, 16.6%-24.2%), and negative predictive value was 99.1% (95% CI, 96.4%-99.8%); for the black-stained LNs, sensitivity was 97.6% (95% CI, 95.3%-98.8%), specificity was 35.4% (95% CI, 33.9%-36.8%), positive predictive value was 11.6% (95% CI, 10.5%-12.8%), and negative predictive value was 99.4% (95% CI, 98.8%-99.7%). Conclusions and Relevance: These findings suggest that CNSI was associated with facilitating the dissection of all positive LNs, which could improve surgical quality. Carbon nanoparticle suspension-guided lymphography may be an alternative to conventional systematic lymphadenectomy for distal gastrectomy.

Endoscopic diagnosis of early-stage primary esophageal small cell carcinoma: Report of two cases.

BACKGROUND: Primary esophageal small cell carcinoma (PESCC) is a highly aggressive malignancy, and its detailed clinical behaviors have remained virtually unknown. Because of the rapid tumor progression, the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice. Currently, only a handful of PESCC cases have been reported. CASE SUMMARY: Case 1: A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy. Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa. As the patient refused to undergo endoscopic resection, neoplasia was detected by endoscopy 1 year later. Case 2: A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital. About 2 wk later, we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa; the submucosal was thinner than normal but still continuous; mucosal hyperemia and erosion were found on the surface of the tumor. Endoscopic submucosal dissection (ESD) was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer. CONCLUSION: Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography. It is easily misdiagnosed as submucosal masses. Endoscopic manifestations should be identified and pathological biopsies should be employed. ESD may be performed to provide an opportunity for early treatment of PESCC.

Feeding behavior toxicity in the marine rotifer Brachionus plicatilis caused by 2,2',4,4'-tetrabromodiphenyl ether (BDE-47): Characteristics and mechanisms.

Polybrominated diphenyl ether contamination in marine environments has received special attention due to its accumulation and magnification in the marine food web and toxicity to organisms. In the present study, a series of short-term toxicological tests were conducted with the marine rotifer Brachionus plicatilis to assess the effects on ingestion and digestive performance after treatment with 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) at nonlethal concentrations under controlled laboratory conditions and to analyze the possible mechanism. The results showed that with accumulation in rotifers, BDE-47 caused a significant decline in the filtration and feeding rates in a concentration-dependent manner. Moreover, the activities of amylase (AMS) and protease were affected, indicating that BDE-47 impaired ingestion and digestion efficiency. BDE-47 exposure did not lead to abnormal microstructures in the main digestive tract (e.g., cilia around the corona, mastax, stomach, digestive gland and esophagus), but the gastric parietal cells shrank, suggesting nutritional deficiency. BDE-47 prominently induced the occurrence of irregular mitochondria at the cilia root, and mitochondrial and isocitrate dehydrogenase activity declined, indicating mitochondrial dysfunction. Furthermore, the activity of ATPase, which catalyzes ATP hydrolysis, decreased as the BDE-47 concentration rose, implying that BDE-47 retarded rotifer ATP dynamics, inevitably interfering with cilia movement to ingest food. Additionally, a significant decline in acetylcholine esterase activity was observed, which led to a hindrance in neurotransmission involved in food intake and digestion. Altogether, our results demonstrated that nonlethal concentrations of BDE-47 could induce feeding depression in rotifers, which is mainly attributed to stymied energy metabolism and nerve conduction.

[Analysis of the parameters about selective anterior fusion of thoracolumbar/lumbar curves in adolescent idiopathic scoliosis].

OBJECTIVE: To establish criteria for AIS of Lenke5 and Lenke6 by an anterior only procedure of the lower curve fusion. METHODS: A retrospective study was conducted between March 1999 and May 2004 to investigate 52 AIS patients of Lenke5 and Lenke6. All the patients were observed 24 years (34 months on average). Many parameters were evaluated. At final assessment, two groups emerged: Group A had satisfactory results (the thoracic curve was reduced) and Group B had just the opposite. RESULTS: Preoperative thoracic curve in group A averaged 33 degrees and 18 degrees after surgery. The lumbar curve averaged 49 degrees before surgery and 21 degrees after surgery. In group B (n = 6), the average thoracic curve was 38 degrees before surgery and 45 degrees after surgery, whereas the lumbar curve averaged 46 degrees before surgery and 25 degrees after surgery. Two of these patients underwent posterior thoracic instrumentation and fusion because of the unreasonable balance. CONCLUSIONS: A successful surgical outcome was dependent on both the flexibility of the thoracic curve and the patients' maturity. The thoracolumbar/lumbar-thoracic (TL/L:T) Cobb ratio in combination with the flexibility of the thoracic curve were the best predictors among the structural indexes.