A survival nomogram model for patients with resectable non-small cell lung cancer and lymph node metastasis (N1 or N2) based on the Surveillance, Epidemiology, and End Results Database and single-center data.

Background: The ability to predict survival in patients with lymph node metastasis has long been elusive. After surgery, the basis for decision-making on the combination treatment of patients is not clear. The purpose of this study was thus to build a survival nomogram model to effectively predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC) and lymph node metastasis. The number of dissected lymph nodes (NDLN), number of positive lymph nodes (NPLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were included in this study to determine the risk factors in patients with advanced NSCLC. Methods: The data of 5,132 patients with NSCLC and lymph node metastasis (N1 or N2) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database according to inclusion and exclusion criteria and used as the training cohort. We enrolled 117 patients from the First Affiliated Hospital, Zhejiang University School of Medicine as the external validation cohort. Receiver operating characteristic (ROC) analyses were performed to determine the best cutoff values for predicting the prognosis of patients with NSCLC. Based on the risk factors affecting prognosis, a nomogram was constructed using univariate and multivariate Cox proportional hazard regression models. The discrimination ability of the nomogram was evaluated with the concordance index (C-index) and calibration curves. For the independent risk factors, survival curves were drawn using Kaplan-Meier analysis. Results: ROC curve analysis showed that the optimal NPLN cut-off value was 4, LNR was 0.26, and LODDS was -0.25, respectively. However, LNR was nonsignificant in multivariate analysis, with a P value of 0.274. The novel survival nomogram model included seven independent risk factors, among which were NPLN, LODDS, and chemotherapy. Model 4, which included N stage, NPLN, and LODDS, had a higher likelihood ratio (LR) and C-index than did the other models. The C-index was 0.648 [95% confidence interval (CI): 0.636-0.659] in the training cohort and 0.807 (95% CI: 0.751-0.863) in the external validation cohort, showing good prognostic accuracy and discrimination ability. According to the median risk score, the patients in the training cohort and external validation cohort were divided into high-risk and low-risk groups, between which significant differences in OS were found. In the training cohort, age, sex, T stage, N stage, NPLN, LODDS, and chemotherapy were significantly associated with OS (P<0.001). In the external validation cohort, T stage, NPLN, LODDS, and chemotherapy were found to be correlated with OS. Conclusions: The NPLN and LODDS nomogram is an accurate survival prediction tool for patients with N1 or N2 NSCLC. Patients with lymph node metastasis can benefit from chemotherapy, but no evidence shows that radiotherapy is necessary for patients with resectable NSCLC.

[Risk factors for hip osteoarthritis after arthroscopy in patients with femoroacetabular impingement].

OBJECTIVE: To investigate the risk factors of hip osteoarthritis（HOA） after hip arthroscopy in patients with femoro-acetabular impingement（FAI） syndrome, and to reduce and prevent HOA. METHODS: From September 2018 to September 2020, 106 patients with FAI underwent hip arthroscopy, including 40 males and 66 females, aged from 20 to 55 years old with an average age of （33.05±10.19） years old. The mechanism of injury included 51 cases for sports injury, 36 for traffic accidents, and 19 for blunt object injury. The duration of the disease ranged from 5 to 19 days with an average of （12.02±3.69） days. All patients were followed up for 18 months. Patients were divided into HOA group （23 cases） and non-HOA group （83 cases） according to the occurrence of HOA. Multivariate Logistic regression was used to analyze the risk factors of HOA after hip arthroscopy in FAI patients. RESULTS: By univariate analysis, aged from 50 to 70 years old, female, body mass index（BMI）> 30 kg·m-2, physical labor, cam type, postoperative infection, last follow-up hip degree of motion （range of motion, ROM） （flexion, abduction, adduction, internal rotation） and Tönnis grade 1 and above of the HOA group were higher than those of the non-HOA group （P<0.05）, and the relative appendicular skeletal muscle index （RASM） was lower than that of non-HOA group（P<0.05）. By multiple Logistic regression analysis, cam type, BMI>30 kg·m-2, last follow-up hip internal rotation ROM and Tönnis grade 1 were risk factors for HOA after hip arthroscopy in FAI patients （P<0.05）. CONCLUSION: FAI classification, body mass index, hip ROM and Tönnis grade are all related to HOA after hip arthroscopy in FAI patients. Follow-up and intervention should be strengthened in high-risk FAI patients to reduce the occurrence of HOA.

Phenotypic and genotypic characterization of Marinobacterium weihaiense sp. nov. and Marinobacterium marinum sp. nov., isolated from marine sediment, and genomic properties of the genus Marinobacterium.

In this study, two novel bacterial strains were isolated from coastal sediment of Weihai, China. The two strains were Gram-stain-negative and facultatively aerobic, designated 3-1745T and A346T. Based on phenotypic, genetic and phylogenetic properties, strains 3-1745T and A346T represent two novel species of the genus Marinobacterium. The results of genome analysis revealed many central carbohydrate metabolism pathways such as gluconeogenesis, pyruvate oxidation, tricyclic acid cycle, pentose phosphate pathway and PRPP biosynthesis in the genus Marinobacterium. The ability of strains 3-1745T and A346T to utilize volatile fatty acids was experimentally confirmed. Polyhydroxyalkanoate synthases (PhaA, PhaB and PhaC) for the synthesis of polyhydroxyalkanoates were prevalent in the genus Marinobacterium. Multiple BGCs (biosynthetic gene clusters) including betalactone, ectoine, ranthipeptide, redox-cofactor, RiPPs (ribosomally synthesized post-translationally modified peptides) and T3PKS (polyketide synthases) in the genome of the genus Marinobacterium were found. Additional genome analyses suggested that the genus Marinobacterium contained diverse potential mechanisms of salt tolerance and mainly utilized oligosaccharides. This is the first report on broad genomic analyses of the genus Marinobacterium with the description of two novel species and potential ecological and biotechnological implications.

An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression.

TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53-PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors. SIGNIFICANCE: We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy. See related commentary by Bhatta and Cooks, p. 1518. This article is highlighted in the In This Issue feature, p. 1501.

The pattern of lymph node metastasis in peripheral pulmonary nodules patients and risk prediction models.

Background: For peripheral pulmonary nodules, the regularity of lymph node (LN) metastasis has not been studied. This study aimed to evaluate the metastasis pattern of intrapulmonary and relevant mediastinal lymph nodes in early-stage lung cancer, and further selected patients who were of low risk of LN metastasis as potential population to receive sub-lobectomy. Methods: This study prospectively included consecutive patients with peripheral clinical T1N0M0 disease who underwent complete resection with LN dissection or sampling from August 2014 to July 2015. The patients were followed up to 15, May 2021. Univariable or multivariable Logistic analysis was used to identify the risk factors. Models predicting LN metastasis risk were conducted. The area under the curve for the receiver operating characteristic curves was used to evaluate the diagnostic value. Disease-free survival and overall survival were compared between groups. Results: Finally, 201 patients were included in this study. For patients with negative tumor-bearing (TB) 13 and 14 station LNs, the positive rate of other lymph node stations was extremely low. Maximum CT value, pleural indentation and CEA level were risk factors for N1 station LNs metastasis. Besides, the factors above and lobulation sign were risk factors for skip metastasis beyond TB 13 and 14 station LNs. We constructed two scoring tables to predict N1 station metastasis and skip metastasis beyond TB 13 and 14 station. The AUC were 0·837 and 0·823, respectively. Based on the first table, 40·9% of patients suffered N1 station LNs metastasis and 27·3% had N2 disease in "high risk group" while the proportion was only 5·7% and 4·5% in "low risk group". For patients with negative TB13 and TB14 station LNs, based on the latter table, 11·1% of patients had N1 stations LNs metastasis and 16·7% had pN2 disease in "high risk group" while only 2·3% patients in "low risk group" suffered this kind of metastasis. Conclusion: For peripheral pulmonary nodules patients, stations 13 and 14 LNs may be the sentinel nodes. For patients with low risk of N1 metastasis and skip metastasis, sub-lobar resection might be sufficient for those who were of negative TB 13 and 14 station LNs.

Venous malformations with severe localized intravascular coagulopathy treated with microwave ablation.

OBJECTIVES: To evaluate the safety and feasibility of microwave ablation for treating venous malformations (VMs) with severe localized intravascular coagulopathy (LIC). PATIENTS AND METHODS: Data for patients with the diagnosis of VMs coupled with severe LIC who underwent color Doppler-guided microwave dynamic ablation between January 2017 and June 2019 were retrospectively reviewed and analyzed. All patients had previously received sclerotherapy or other treatments with poor outcomes and gradual aggravation of coagulation abnormalities. Microwave treatment with "dynamic ablation" was performed with real-time color Doppler monitoring and was repeated if necessary after 3 months. Low-molecular-weight heparin (LMWH) was used to control consumptive coagulopathy. The therapeutic efficacy including coagulation function and lesion size was evaluated using the four-level scale developed by Achauer. RESULTS: Among 15 patients with extensive diffuse or multiple VMs, 10 patients presented with lesions in a single lower extremity, one in both lower extremities and the perineum, one in both upper extremities and the trunk, and three with multiple lesions. The patients underwent a total of 74 microwave ablation sessions, with an average of 4.9 sessions per person. Coagulation abnormalities were temporarily aggravated in 59 sessions within the first seven days post-ablation but improved to grade II (fair) a week later. From six months to three years after the ablation, the lesions improved to grade IV (excellent) in one patient, grade III (good) in six patients, and grade II (fair) in eight patients. Moreover, the coagulation function improved to grade IV in four patients, grade III in eight patients, and grade II in three patients, resulting in an efficiency rate of 80% (12/15). Post-ablation complications included fever, hemoglobinuria, and elevations in aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase. The patients with fever and hemoglobinuria recovered after specific therapeutic measures, but elevations in aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase recovered spontaneously without further interventions. CONCLUSIONS: Ablation coupled with anticoagulation can effectively treat VMs in patients with severe LIC and improve the long-term coagulation function.

Analysis of 18 complex diffuse arteriovenous malformation cases treated with percutaneous radiofrequency ablation.

BACKGROUND: The aim of the present study is to evaluate the short-term efficacy and feasibility of radiofrequency ablation in the treatment of complex diffuse arteriovenous (AV) malformations. METHODS: The data of 18 patients (8 male and 10 female) with complex AV malformations treated between December 2014 and June 2019 were analyzed retrospectively. The lesion area was 10 × 7 cm ~ 28 × 30 cm. Under duplex ultrasound guidance, the site with the most abundant blood flow signals in the lesion was percutaneously punctured with the radiofrequency ablation needle (electrode). The impedance automatic adjustment mode was adopted, and ablation was monitored usingduplex ultrasoundduring the entire process. RESULTS: Of the included patients, 1 had a high fever after two rounds of treatment, 2 had transient hemoglobinuria, and 1 had tissue necrosis in the original ruptured tumor area as well as a penetrating defect in the cheek, which was repaired with a pedicled trapezius myocutaneous flap. In 9 patients who experienced bleeding, the bleeding stopped after one round of treatment. During the follow-up period of 1-5 years, there were 0 grade I (poor) cases, 0 grade II (medium) cases, 7 grade III (good) cases, and 11 grade IV (excellent) cases. CONCLUSION: The "high power and continuous" radiofrequency ablation technique conducted under real-time duplex ultrasoundmonitoring can completely destroy the deep core lesions of AV malformations and effectively control life-threatening massive hemorrhage; it is an effective alternative treatment method for complex diffuse AV malformations in which interventional embolization, sclerotherapy, and surgery are ineffective.

Standards of care for Kasabach-Merritt phenomenon in China.

Kasabach-Merritt phenomenon (KMP) is a rare disease that is characterized by severe thrombocytopenia and consumptive coagulation dysfunction caused by kaposiform hemangioendothelioma or tufted hemangioma. This condition primarily occurs in infants and young children, usually with acute onset and rapid progression. This review article introduced standardized recommendations for the pathogenesis, clinical manifestation, diagnostic methods and treatment process of KMP in China, which can be used as a reference for clinical practice.

Hsa_circ_0088233 Alleviates Proliferation, Migration, and Invasion of Prostate Cancer by Targeting hsa-miR-185-3p.

Prostate cancer is the most common malignant tumor of the urinary system. The mechanisms of the initiation and progression of prostate cancer have not been fully elucidated. Increasing evidence suggests that circular RNAs (circRNAs) are involved in cancer pathogenesis. In this study, we aimed to identify differentially expressed circRNAs in prostate cancer tissues and explored the role of circRNAs in the pathogenesis of prostate cancer. By screening a circRNA microarray assay, we found that circ_0088233 was upregulated in prostate cancer tissues compared to adjacent normal tissues, and this upregulation can be verified in 46 pairs of prostate cancer and adjacent normal tissues examined using quantitative reverse transcription-PCR. The level of circ_0088233 correlated with the TNM stage. Knockdown of circ_0088233 reduced cell proliferation, migration, invasion, and induced G1 phase arrest and apoptosis. In addition, miR-185-3p was identified as the downstream target of circ_0088233 using luciferase reporter assays and a biotinylated circ_0088233 probe pull-down assay. The miR-185-3p level showed a negative correlation with the circ_0088233 level in prostate cancer tissues. Overexpression of circ_0088233 blocked the effects of miR-185-3p on cell proliferation, migration, invasion, cell cycle, and apoptosis. In conclusion, circ_0088233 may function as an oncogene and play an oncogenic role by sponging hsa-miR-185-3p. This study increases the understanding of circRNAs in the progression of prostate cancer. These results implicate circ_0088233 as a potential therapeutic target for prostate cancer.

Dienedioic acid as a useful diene building block via directed Heck-decarboxylate coupling.

The concise construction of diene scaffolds is quite useful in the synthesis of polyenes. Many diene building blocks have been developed based on Suzuki, Still and Hiyama couplings. Herein, the commercially available and environmentally friendly compound dienedioic acid is used as a diene building block. Broad substrate scope, good functional group tolerance, and late-stage derivatization of complex drug molecules are achieved. Different moieties can be conveniently introduced to both sides. Piperine and the methyl ester of azoxymycin C are each prepared in three steps. Additionally, one product shows promising anticancer activities in leukemia K562 and MV-4-11 cells. Mechanistic studies indicate that the reaction proceeds through a Heck-decarboxylate coupling procedure, and the carboxylic group acts as a directing group to promote the reaction and control regioselectivity. Our research suggests that dienedioic acid can serve as a good alternative for diene preparation via a directed Heck-decarboxylate coupling.

Fruit and vegetable intake and liver cancer risk: a meta-analysis of prospective cohort studies.

The associations of vegetable and fruit intake with liver cancer risk have been inconsistent based on epidemiological studies. The present study aimed to quantitatively evaluate these associations with prospective cohort studies. A systematic literature search was performed with PubMed and Scopus databases up to June 2019. Multivariate-adjusted relative risks (RRs) with a corresponding 95% confidence interval (CI) for the highest versus lowest category were pooled by using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Dose-response analysis was conducted by using the variance weighted least squares regression model. Nine independent prospective cohort studies with 1703 liver cancer events and 1 326 176 participants were included for data synthesis. The summary estimates showed that higher vegetable intake was associated with a 39% (95%CI: 0.50, 0.75) reduction in liver cancer risk, with no significant between-study heterogeneity (P = 0.057). Dose-response analysis indicated that the risk of liver cancer was reduced by 4% (95%CI: 0.97, 0.95; P for trend <0.001) with a 100 gram per day increment of vegetable intake. Subgroup analysis showed that higher intakes of vegetables were associated with a 50% (95%CI: 0.35, 0.72) reduction of liver cancer risk in males, but not in females. However, a non-significant association was found between fruit intake and liver cancer risk. The present study provides strong evidence that higher intakes of vegetables would have beneficial effects on the prevention of liver cancer, especially for males.

Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer.

Although osimertinib, an EGFR tyrosine kinase inhibitor, has become the standard therapy for treating non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, upregulation of MCL-1 induces acquired resistance to osimertinib. Bufalin, a natural digoxin-like ingredient isolated from a traditional Chinese medicine Chan Su, has been shown to downregulate MCL-1 in NSCLC cells. However, whether bufalin reverses this acquired resistance to osimertinib in NSCLC cells remains unclear. In this study, bufalin reduced cell viability and promoted apoptosis in osimertinib-resistant cells. Moreover, co-treatment with bufalin and osimertinib restored the sensitivity of osimertinib-resistant cells to osimertinib-induced growth regression and apoptosis in vitro and in vivo. Mechanistically, MEK/ERK-dependent MCL-1 phosphorylation and Ku70-mediated MCL-1 overexpression confer osimertinib resistance in EGFR-mutant NSCLC cells. In osimertinib-resistant cells, bufalin modulates Ku70-mediated MCL-1 degradation, but not MEK/ERK/MCL-1 signaling. In conclusion, our study suggests that bufalin eliminates resistance to osimertinib by inhibiting Ku70-mediated MCL-1 overexpression, indicating that a combination of osimertinib and bufalin could be an effective additional treatment to overcome acquired resistance to osimertinib in NSCLC cells.

Catalytic Selective Oxidative Coupling of Secondary N-Alkylanilines: An Approach to Azoxyarene.

Azoxyarenes are among important scaffolds in organic molecules. Direct oxidative coupling of primary anilines provides a concise fashion to construct them. However, whether these scaffolds can be prepared from secondary N-alkylanilines is not well explored. Here, we present a catalytic selective oxidative coupling of secondary N-alkylaniline to afford azoxyarene with tungsten catalyst under mild conditions. In addition, azoxy can be viewed as a bioisostere of alkene and amide. Several "azoxyarene analogues" of the corresponding bioactive alkenes and amides showed comparable promising anticancer activities.

Notch signaling pathway regulates CD4+CD25+CD127dim/- regulatory T cells and T helper 17 cells function in gastric cancer patients.

Regulatory T cells (Tregs) and T helper 17 (Th17) cells contribute to cancer progression and prognosis. However, regulatory factors associated with Tregs-Th17 balance were not completely understood. We previously demonstrated an immune-modulatory capacity by Notch signaling inactivation to reverse Tregs-Th17 disequilibrium in chronic hepatitis C. Thus, the aim of current study was to assess the role of Notch signaling in modulation Tregs and Th17 cells function in gastric cancer (GC) patients. A total of 51 GC patients and 18 normal controls (NCs) were enrolled. Notch1 and Notch2 mRNA expressions were semiquantified by real-time polymerase chain reaction. Tregs/Th17 percentages, transcriptional factors, and cytokines production were investigated in response to the stimulation of Notch signaling inhibitor DAPT. Both Notch1 and Notch2 mRNA expressions were elevated in GC tissues and peripheral bloods in GC patients. CD4+CD25+CD127dim/- Tregs and Th17 cells percentage was also elevated in GC patients compared with in NCs. DAPT treatment did not affect frequency of either circulating Tregs or Th17 cells, however, reduced FoxP3/RORγt mRNA expression and interleukin (IL)-35/IL-17 production in purified CD4+ T cells from GC patients. Moreover, blockade of Notch signaling also inhibited the suppressive function of purified CD4+CD25+CD127dim/- Tregs from GC patients, which presented as elevation of cellular proliferation and IL-35 secretion. The current data further provided mechanism underlying Tregs-Th17 balance in GC patients. The link between Notch signaling and Th cells might lead to a new therapeutic target for GC patients.

A novel tumor suppressor SPINK5 targets Wnt/ß-catenin signaling pathway in esophageal cancer.

Esophageal cancer is one of the most common tumor in the world, and the morbidity rate is as high as 100/100 000 in some parts of China. Therefore, it is important and urgent to explore the pathogenesis of esophageal cancer and find new therapeutic targets for esophageal cancer. In this study, we found that a novel tumor suppressor SPINK5 is significantly reduced in the development of esophageal cancer, and is closely related to the pathological differentiation and lymph node metastasis of esophageal cancer via bioinformatics analysis and esophageal cancer tissue array. Further studies have found that SPINK5 is closely related to Wnt/ß-catenin signaling pathway by bioinformatics analysis and western blot. In esophageal cancer cells, SPINK5 overexpression can inhibit Wnt/ß-catenin signaling pathway. Combined with LiCl or MG-132 treatment, SPINK5 can inhibit GSK3ß phosphorylation and promote ß-catenin protein degradation, thus inhibit Wnt/ß-catenin signaling pathway. In vivo study, SPINK5 overexpression can significantly inhibit the growth of esophageal cancer cells. Our study shows that SPINK5 can inhibit the proliferation, migration, and invasion of esophageal cancer cells by inhibiting Wnt/ß-catenin signaling pathway, and thus plays an important role in the development of esophageal cancer, and may serve as a treatment target of esophageal cancer.

Primary hepatic leiomyosarcoma successfully treated by transcatheter arterial chemoembolization: A case report.

BACKGROUND: Primary hepatic leiomyosarcoma is rare and reported sporadically, with less than 40 such cases have been reported in the English-language literature. Although it is reported to be associated with acquired immune deficiency syndrome, Epstein-Barr virus infection, Hodgkin's lymphoma, immunosuppression after organ transplantation, and hepatitis C virus-related liver cirrhosis, the precise steps leading to leiomyosarcoma have not been fully identified. Therapeutic strategies include liver wedge resection or lobectomy, chemotherapy, radiotherapy and liver transplantation; however, the prognosis of primary hepatic leiomyosarcoma is dismal. CASE SUMMARY: We describe here the first case of primary hepatic leiomyosarcoma successfully treated by transcatheter arterial chemoembolization (TACE). The patient was a 68-year-old woman who presented with right upper quadrant pain and weight loss over the past 5 wk before admission. Abdominal computed tomography (commonly known as CT) and ultrasonography showed a mixed echoic mass measuring about 10 cm × 7 cm occupying the right lobe of the liver. Exploratory laparotomy was performed 1 wk after admission. The tumor was unresectable and biopsy was performed. Based on rapid frozen-section and histopathological examination, a final diagnosis of primary hepatic leiomyosarcoma was established. TACE was performed 2 wk later. The postoperative course was uneventful and the patient was discharged on day 7 after the operation. Contrast-enhanced CT showed that the tumor significantly shrunk with satisfactory lipiodol deposition. The patient has been followed up for 82 mo until now, and no progressive enlargement of the tumor or distal metastasis was observed. CONCLUSION: TACE is a safe and effective treatment for primary hepatic leiomyosarcoma. The therapeutic effect of TACE combined with surgical resection should be further assessed.

Effects of EPA and DHA on blood pressure and inflammatory factors: a meta-analysis of randomized controlled trials.

The present study aimed to clarify whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on blood pressure and inflammatory mediators. A systematic literature search was conducted in PubMed and Scopus updated to Apr. 2018. The mean changes in risk factors of chronic diseases were calculated as weighted mean difference (WMD) by using a random-effects model. Twenty randomized controlled trials (RCTs) were included. The summary estimate showed that EPA intervention significantly reduced systolic blood pressure (SBP) (-2.6 mmHg; 95%confident interval (CI): -4.6, -0.5 mmHg), especially in subjects with dyslipidemia (-3.8 mmHg; 95%CI: -6.7, -0.8 mmHg). The pooled effect indicated that supplemental DHA exerted a significant reduction in diastolic blood pressure (DBP) in subjects with dyslipidemia (-3.1 mmHg; 95%CI: -5.9, -0.2 mmHg). Both EPA (-0.56 mg/L; 95%CI: -1.13, 0.00) and DHA (-0.5 mg/L; 95%CI: -1.0, -0.03) significantly reduced the concentrations of C-reactive protein (CRP), respectively, especially in subjects with dyslipidemia and higher baseline CRP concentrations. Given that limited trials have focused on EPA or DHA intervention on concentrations of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, further RCTs should be explored on these inflammatory factors. The present meta-analysis provides substantial evidence that EPA and DHA have independent (blood pressure) and shared (CRP concentration) effects on risk factors of chronic diseases, and high-quality RCTs with multi-center and large simple-size should be performed to confirm the present findings.

Interplay between long noncoding RNA ZEB1-AS1 and miR-101/ZEB1 axis regulates proliferation and migration of colorectal cancer cells.

Long noncoding RNAs (lncRNAs) are dysregulated in many diseases. MicroRNA-101 (miR-101) functions as a tumor suppressor by directly targeting ZEB1 in various cancers. However, the potential mechanism of lncRNA ZEB1-AS1 and miR-101/ZEB1 axis in CRC remains unknown. In this study, we further investigated the potential interplay between miR-101/ZEB1 axis and lncRNA ZEB1-AS1 in colorectal cancer (CRC). Results showed that ZEB1-AS1 was upregulated in CRC tissues and cells. MiR-101 was downregulated in CRC tissues and negatively correlated with ZEB1-AS1 and ZEB1 expression levels in CRC. Functional experiments showed that, consistent with ZEB1-AS1 depletion, miR-101 overexpression and ZEB1 depletion inhibited the proliferation and migration of CRC cells. Overexpression of miR-101 partially abolished the effects of ZEB1-AS1 on the proliferation and migration of these cells. Moreover, combined ZEB1-AS1 depletion and miR-101 overexpression significantly inhibited cell proliferation and migration of the CRC cells. Hence, ZEB1-AS1 functioned as a molecular sponge for miR-101 and relieved the inhibition of ZEB1 caused by miR-101. This study revealed a novel regulatory mechanism between ZEB1-AS1 and miR-101/ZEB1 axis. The interplay between ZEB1-AS1 and miR-101/ZEB1 axis contributed to the proliferation and migration of CRC cells, and targeting this interplay could be a promising strategy for CRC treatment.

Modified Abietane Diterpenoids from Whole Plants of Selaginella moellendorffii.

A new modified abietane diterpenoid, (3S,4S,5R,10S)-18(4→3)-abeo-3,4,12,18-tetrahydroxy-8,11,13-abietatrien-7-one (1), and two novel dimers, selaginedorffones A (2) and B (3), featuring a new cyclohexene moiety that was biogenetically constructed from two modified abietane diterpenoids through a Diels-Alder reaction were obtained from a methanolic extract of Selaginella moellendorffii, a traditional Chinese herb. The structures of 1-3 were identified by a combination of NMR spectroscopic analysis and ECD calculations. In the present study, diterpenoids were identified from S. moellendorffii for the first time, which supports the presence of diterpene synthases in this plant. These three diterpenoids (1-3) were evaluated for their growth-inhibitory activities against several human cancer cell lines. Of these substances, selaginedorffone B (3) showed cytotoxicity against the MCF-7 human-breast-cancer-cell line (IC50 9.0 µM).

Synthesis and evaluation of a class of 1,4,7-triazacyclononane derivatives as iron depletion antitumor agents.

Iron depletion has been confirmed as an efficient strategy for cancer treatment. In the current study, a series of 1,4,7-triazacyclononane derivatives HE-NO2A, HP-NO2A and NE2P2A, as well as the bifunctional chelators p-NO2-PhPr-NE3TA and p-NH2-PhPr-NE3TA were synthesized and evaluated as iron-depleting agents for the potential anti-cancer therapy against human hepatocellular carcinoma. The cytotoxicity of these chelators was measured using hepatocellular cancer cells and compared with the clinically available iron depletion agent DFO and the universal metal chelator DTPA. All these 1,4,7-triazacyclononane-based chelators exhibited much stronger antiproliferative activity than DFO and DTPA. Among them, chelators with phenylpropyl side chains, represented by p-NO2-PhPr-NE3TA and p-NH2-PhPr-NE3TA, displayed the highest antiproliferative activity against HepG2 cells. Hence, these compounds are attractive candidates for the advanced study as iron depletion agents for the potential anti-cancer therapy, and could be further in conjugation with a targeting moiety for the future development in targeted iron depletion therapy.