Progress of Antimicrobial Mechanisms of Stilbenoids.

Antimicrobial drugs have made outstanding contributions to the treatment of pathogenic infections. However, the emergence of drug resistance continues to be a major threat to human health in recent years, and therefore, the search for novel antimicrobial drugs is particularly urgent. With a deeper understanding of microbial habits and drug resistance mechanisms, various creative strategies for the development of novel antibiotics have been proposed. Stilbenoids, characterized by a C6-C2-C6 carbon skeleton, have recently been widely recognized for their flexible antimicrobial roles. Here, we comprehensively summarize the mode of action of stilbenoids from the viewpoint of their direct antimicrobial properties, antibiofilm and antivirulence activities and their role in reversing drug resistance. This review will provide an important reference for the future development and research into the mechanisms of stilbenoids as antimicrobial agents.

[Retracted] circNSUN2 promotes the malignant biological behavior of colorectal cancer cells via the miR­181a­5p/ROCK2 axis.

Following the publication of the above article, a concerned reader drew to the Editor's attention that the data showing the results of TUNEL staining of tumours featured in the four panels of Fig. 2G on p. 4, and potentially some of the photographs of the tumours shown in Fig. 2F, were strikingly similar to data appearing in different form in another article written by different authors that had already been submitted for publication elsewhere prior to the submission of this paper to Oncology Reports. In view of the fact that certain of these data had already apparently been submitted for submission in a different journal, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 46: 142, 2021; DOI: 10.3892/or.2021.8093].

Inhibitory Mechanism of Pinosylvin Monomethyl Ether against Aspergillus flavus.

Control of Aspergillus flavus is beneficial for the agricultural economy and food safety. Stilbenes exhibit antifungal properties through an unknown mechanism. Here, six stilbenes isolated from Cajanus cajan were screened for anti-A. flavus activity. Among them, pinosylvin monomethyl ether (PME) showed the strongest anti-A. flavus activity and has a broad antifungal spectrum with negligible hemolysis within the concentration range measured. PME inhibited the spore germination of A. flavus and the accumulation of aflatoxin B1. Mechanistic studies showed that PME could bind the cell membrane phospholipids, resulting in increased permeability and decreased fluidity. Further metabolic analysis showed that PME caused the lysis of cell membranes and subsequent collapse of spores, which resulted in a cell wall autolysis-like phenotype. Structure-activity relationship analysis revealed the importance of maintaining amphiphilicity harmony by substituent groups for the antifungal activity of stilbenes. Together, natural stilbenes are promising antifungal lead compounds worthy of further exploration and research for potential application in the food, pharmaceutical, and agricultural industries.

Divergent responses of soil microbial functional groups to long-term high nitrogen presence in the tropical forests.

A massive rise in atmospheric nitrogen deposition (ND) has threatened ecosystem health through accelerating soil nitrogen (N) cycling rates. While soil microbes serve a crucial function in soil N transformation, it remains poorly understood on how excess ND affects microbial functional populations regulating soil N transformation in tropical forests. To address this gap, we conducted 13-year N (as NH4NO3) addition experiments in one N-rich tropical primary forest (PF) and two N-poor tropical reforested forests (rehabilitated and disturbed) in South China. Based on our data, 13-year N introduction markedly enhanced soil N2O generation in all forests, regardless of soil N status, but microbial functional groups showed divergent responses to excess N addition among the studied forests. In the PF, long-term N introduction markedly decreased presence of bacterial 16S rRNA gene, nitrifier (amoA) and denitrifier genes (nirK, nirS and nosZ) and bacteria/fungi ratio, which could be attributed to the decreases in soil pH, dissolved organic carbon to N ratio and understory plant richness. In the two reforested forests, however, long-term N introduction generally did neither alter soil properties nor the abundance of most microbial groups. We further found that the elevated N2O generation was related to the increased soil N availability and decreased nosZ abundance, and the PF has the highest N2O generation than the other two forests. Overall, our data indicates that the baseline soil N status may dominate response of microbial functional groups to ND in tropical forests, and N-rich forests are more responsive to excess N inputs, compared to those with low-N status. Forests with high soil N status can produce more N2O than those with low-N status. With the spread of elevated ND from temperate to tropical zones, tropical forests should merit more attention because ecosystem N saturation may be common and high N2O emission will occur.

2-Pyrones from endophytic fungus Diaporthe foeniculina BZM-15.

Foeniculins A-C (1-3) together with a pair of enantiomers (±)-foeniculin D (4) were isolated from endophytic fungus Diaporthe foeniculina BZM-15. Their structures including absolute configurations were unambiguously established by extensive interpretation of the NMR and HR-ESI-MS data, ECD measurements powered by molecular calculations, as well as Mo2(OAc)4 mediated CD methodology. The cytotoxic activity assay disclosed that these compounds didn't show any noticeable cytotoxic activity.[Formula: see text].

circNSUN2 promotes the malignant biological behavior of colorectal cancer cells via the miR­181a­5p/ROCK2 axis.

Aberrant expression of circular RNAs (circRNAs) has been demonstrated to be related to the development of colorectal cancer (CRC), the third most common cancer worldwide. However, the mechanism of the effect of circRNA NOP2/Sun domain family, member 2 (circNSUN2) on the malignant biological behavior of CRC remains unclear. In the present study, the expression of circNSUN2 and microRNA (miR)­181a­5p was detected by RT­qPCR. The expression of Rho­associated coiled­coil­containing protein kinase 2 (ROCK2) was measured by western blotting. Cell proliferation was detected by CCK­8 assay. The cell apoptosis rate was measured by flow cytometry. Cell migration ability was evaluated by Transwell assay. The interactions between circNSUN2, miR­181a­5p and ROCK2 were verified by dual­luciferase reporter assay. The results revealed that circNSUN2 was highly expressed in CRC tissues and cell lines. Knockdown of circNSUN2 inhibited the malignant biological behavior of CRC in vivo and in vitro. Moreover, miR­181a­5p was revealed to be a target gene of circNSUN2, and the expression of ROCK2 was negatively regulated by miR­181a­5p. Knockdown of circNSUN2 inhibited proliferation and migration, and induced apoptosis of CRC cells and suppressed tumor growth by targeting miR­181a­5p to decrease ROCK2 expression. In conclusion, circNSUN2 promoted the progression of CRC by sponging miR­181a­5p to increase the expression of ROCK2.

Long non-coding RNA LUCAT1 promotes proliferation and invasion in gastric cancer by regulating miR-134-5p/YWHAZ axis.

PURPOSE: The aim of this study was to research the function of lncRNA LUCAT1 in gastric cancer. METHODS: Human gastric cancer tissues and paracancer tissues were obtained from 98 patients undergoing surgical resection in our hospital. The human gastric cancer cell lines (HGC27, BGC823, MGC803, SGC7901 and AGS), and normal gastric mucosal cell line GSE1 were used to research the role of lncRNA LUCAT1. ShRNAs specifically targeting lncRNA LUCAT1, miR-134-5p mimic, miR-134-5p inhibitor and their related controls were transfected into cells. Quantitative real-time PCR was used to detect the expression of lncRNA LUCAT1, miR-134-5p and YWHAZ. The cell proliferation of SGC7901 cells was determined by CCK8 kit. Colony formation assay was undertaken. Cell apoptosis assay was processed using the Annexin V-FITC / propidium iodide (annxinV/PI) apoptosis detection kit. Migration and invasion were detected by transwell assay. Tumor xenograft model was conducted to calculate the size and weight of the tumors. Luciferase reporter assay was used to confirm the interactions among lncRNA LUCAT1, miR-134-5p and YWHAZ. RESULTS: LncRNA LUCAT1 was confirmed to be highly expressed in gastric cancer. Patients with high LUCAT1 level displayed short overall survival and disease-free survival periods. LUCAT1 knockdown or miR-134-5p overexpression decreased the proliferation, colony formation, migration and invasion of SGC7901 cells. CONCLUSIONS: LncRNA LUCAT1 could promote proliferation and invasion of gastric cancer by regulating miR-134-5p/YWHAZ axis.

LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p.

Up to date, the mechanism of gastric cancer (GC) development is poorly understood. This study was to demonstrate the effects of LINC00339 on GC progression. Here, we found that LINC00339 was overexpressed expressed in GC tissues and predicted poor outcome. By CCK8, colony formation and Transwell assays, we showed LINC00339 knockdown suppressed GC cell proliferation, migration, and invasion in vitro. Flow cytometry analysis (FACS) indicated that LINC00339 knockdown induced tumor cell apoptosis. Besides, we utilized the xenograft assay and found that LINC00339 depletion led to decreased tumor growth in vivo. Mechanistically, miR-377-3p was found to be inhibited by LINC00339. And LINC00339 suppressed miR-377-3p to upregulate DCP1A, which consequently promoted GC progression. In conclusion, LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p.

Efficiency of bursectomy in patients with resectable gastric cancer: An updated meta-analysis.

AIMS: A meta-analysis was performed to evaluate the safety and efficiency of bursectomy for patients with gastric cancer. METHOD: A literature search was performed in PubMed, EMBASE, and the Cochrane Library databases,China National Knowledge Infrastructure databases, China Science and Technology Journal(CSTJ) database and ASCO proceedings for clinical research that compared bursectomy with non-bursectomy published before July 2017. Operative time, blood loss, the number of dissected lymph nodes, complications, mortality, length of hospital stay, recurrence rate, overall survival and recurrence-free survival were compared using weighted mean differences(WMD) and relative risks(RR). RevMan 5.3. software was used for statistical analysis. RESULTS: Fifteen studies including 4858 patients were included for the analysis (2687 in the bursectomy group(BT), 2171 in the non-bursectomy group(NB)). The bursectomy group was associated with longer operative time (P < 0.00001)and more blood loss (P = 0.003)compared with NB. No statistically significant difference was observed in the number of dissected lymph nodes (P = 0 0.08), the length of hospital stay (P = 0 0.30), rate of complications(P = 0.07), mortality (P = 0.15), recurrence rate (P = 0.44)between the bursectomy group and the non-bursectomy group. Bursectomy did not have a significant effect on overall survival and recurrence-free survival. CONCLUSIONS: Gastrectomy with bursectomy is not superior to non-bursectomy in terms of survival,bursectomy is not recommended as a standard surgery for resectable cT3 or cT4 gastric cancer.

The efficiency and safety of trastuzumab for advanced gastric and gastroesophageal cancer: a meta-analysis of five randomized controlled trials.

A meta-analysis was performed to examine the efficiency and safety of trastuzumab in patients with advanced gastric and gastroesophageal cancer (AGC). By searching multiple databases from 1990 to March 2016, all randomized controlled trials (RCTs) which compared the effect of trastuzumab-combined chemotherapy (TC) versus chemotherapy alone (CT) in gastric cancer would be included. Five RCTs with a total of 875 patients were included. Trastuzumab can improve the overall survival (OS) rate, progression-free survival (PFS), one-year survival rate, two-year survival rate and overall response rate (ORR) of patients with AGC. There were no difference between the two arms in terms of grade 3/4 adverse effects, such as vomiting, nausea, neutropenia, thrombocytopaenia and anemia. Diarrhea increased in TC group. Trastuzumab can significantly improve the survival rate, PFS, ORR of patients with AGC. It is safe and feasible and can be tolerated. It needs further prospective multinational multicenter RCTs with large samples to define the clinical benefits of trastuzumab.

XELOX vs. FOLFOX in metastatic colorectal cancer: An updated meta-analysis.

This meta-analysis aims to evaluate chemotherapy with XELOX (capecitabine plus oxaliplatin) versus FOLFOX (fluorouracil plus oxaliplatin) as a treatment for metastatic colorectal cancer (mCRC) in terms of efficacy and safety. Only randomized controlled trials (RCTs) comparing XELOX versus FOLFOX were included. A total of 4,363 patients from eight RCTs were available for analysis. Pooled analysis revealed that there were no statistical differences between both arms in OS, and ORR. XELOX arm had a higher incidence of thrombocytopenia, hand-foot syndrome, and diarrhea, whereas neutropenia had a higher incidence in the FOLFOX group. For mCRC, the effect of XELOX is similar to FOLFOX.

Robotic versus laparoscopic total mesorectal excision for rectal cancer: a meta-analysis of eight studies.

BACKGROUND: Robotic surgery has been used successfully in many branches of surgery, but there is little evidence in the literature on its use in rectal cancer (RC). We conducted this meta-analysis of randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) to evaluate whether the safety and efficacy of robotic total mesorectal excision (RTME) in patients with RC are equivalent to those of laparoscopic TME (LTME). METHODS: Pubmed, Embase, Cochrane Library, Ovid, and Web of Science databases were searched. Studies clearly documenting a comparison of RTME with LTME for RC were selected. Operative and recovery outcomes, early postoperative morbidity, and oncological parameters were evaluated. RESULTS: Eight studies were identified that included 1229 patients in total, 554 (45.08 %) in the RTME group and 675 (54.92 %) in the LTME group. Compared with LTME, RTME was associated with lower conversion rate (OR 0.23, 95 % CI [0.10, 0.52]; P = 0.0004), lower positive rate of circumferential resection margins (CRM) (2.74 % vs 5.78 %, OR 0.44, 95 % CI [0.20, 0.96], P = 0.04), and lesser incidence of erectile dysfunction (ED) (OR 0.09, 95 % CI [0.02, 0.41]; P = 0.002). Operation time, estimated blood loss, recovery outcome, postoperative morbidity and mortality, length of hospital stay, number of lymph nodes harvested, distal resection margin (DRM), proximal resection margin (PRM), and local recurrence had no significant differences between the two groups. CONCLUSIONS: RTME is safe and feasible and may be an alternative treatment for RC. More international multicenter prospective large sample RCTs investigating the long-term oncological and functional outcomes are needed to determine the advantages of RTME over LTME in RC.

WITHDRAWN: Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: An updated meta-analysis of 12 randomized controlled trials.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Characterization of side population cells isolated from the colon cancer cell line SW480.

Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many types of cell lines and tissues have demonstrated the presence of SP cells, including colon cancer cell lines. This study aimed to identify cancer stem cells (CSCs) in the SP of the colon cancer cell line SW480. SP cells were isolated by fluorescence-activated cell sorting (FACS), followed by serum-free medium (SFM) culture. The self-renewal, differentiated progeny, clone formation, proliferation, invasion ability, cell cycle, chemosensitivity and tumorigenic properties in SP and non-SP (NSP) cells were investigated through in vitro culture and in vivo serial transplantation. The expression profiles of ATP-binding cassette (ABC) protein transporters and stem cell-related genes were examined by RT-PCR and western blot analysis. The human colon cancer cell lines SW480, Lovo and HCT116 contain 1.1 ± 0.10, 0.93 ± 0.11 and 1.33 ± 0.05% SP cells, respectively. Flow cytometry analysis revealed that SP cells could differentiate into SP and NSP cells. SP cells had a higher proliferation potency and CFE than NSP cells. Compared to NSP cells, SP cells were also more resistant to CDDP and 5-FU, and were more invasive and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA and protein expression of ABCG2, MDR1, OCT-4, NANOG, SOX-2, CD44 and CD133. SP cells isolated from human colon cancer cell lines harbor CSC properties that may be related to the invasive potential and therapeutic resistance of colon cancer.

An updated meta-analysis of randomized controlled trial assessing the effect of neoadjuvant chemotherapy in advanced gastric cancer.

Patients with locally advanced gastric cancer (AGC) have a poor outcome. We performed an updated meta-analysis to assess the effect of neoadjuvant chemotherapy (NAC). By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC combined surgery versus surgery alone in advanced gastric and gastroesophageal cancer would be included. All calculations and statistical tests were performed. Twelve RCTs with a total of 1,820 patients were included. All patients had resectable gastric or gastroesophageal cancer and received NAC. NAC can slightly improve the survival rate [OR = 1.32, 95% confidence interval (CI): 1.07-1.64, P = 0.01], little, or no significant benefits were suggested in subgroup analyses between different population and regimens either. It can significantly improved the 3-year progression-free survival (PFS) [OR: 1.85 (1.39, 2.46), p < .0001], tumor down-staging rate [OR: 1.71 (1.26, 2.33), p = .0006] and R0 resection rate [OR: 1.38 (1.08, 1.78) p = .01] of patients with AGC. There were no difference between the two arms, in terms of relapse rates [OR: 1.03 (0.60, 1.78), p = 0.92], operative complications [OR: 1.20 (0.90, 1.58), p = 0.21], perioperative mortality [OR: 1.14 (0.64, 2.05), p = 0.65], and grade 3/4 adverse effects. NAC can significantly down-stage the tumor and improve R0 resection rate of patients with gastric and gastroesophageal cancer. It is safe and feasible, and can be tolerated. NAC can slightly improve the survival rate. It needs further prospective multinational multicenter RCTs to define the clinical benefits of NAC and the most effective strategies for gastric and gastroesophageal cancer.

Robotic versus laparoscopic total mesorectal excision for rectal cancer: a meta-analysis.

BACKGROUND: Robotic surgery has been used successfully in many branches of surgery; but there is little evidence in the literature on its use in rectal cancer (RC). We conducted this meta-analysis that included randomized controlled trials and nonrandomized controlled trials of robotic total mesorectal excision (RTME) versus laparoscopic total mesorectal excision (LTME) to evaluate whether the safety and efficacy of RTME in patients with RC are equivalent to those of LTME. MATERIALS AND METHODS: Pubmed, Embase, Cochrane Library, Ovid, and Web of Science databases were searched. Studies clearly documenting a comparison of RTME with LTME for RC were selected. Operative and recovery outcomes, early postoperative morbidity, and oncological parameters were evaluated. RESULTS: Eight studies were identified that included 1229 patients in total, 554 (45.08%) in the RTME and 675 (54.92%) in the LTME. Meta-analysis suggested that the conversion rate to open surgery in RTME was significantly lower than in LTME (P = 0.0004). There were no significant differences in operation time, estimated blood loss, recovery outcome, postoperative morbidity and mortality, length of hospital stay, and the oncological accuracy of resection and local recurrence between the two groups. The positive rate of circumferential resection margins (P = 0.04) and the incidence of erectile dysfunction (P = 0.002) were lower in RTME compared with LTME. CONCLUSIONS: RTME for RC is safe and feasible, and the short- and medium-term oncological and functional outcomes are equivalent or preferable to LTME. It may be an alternative treatment for RC. More multicenter randomized controlled trials investigating the long-term oncological and functional outcomes are required to determine the advantages of RTME over LTME in RC.

MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling pathway in human colorectal cancer cells.

The aim of this study was to determine a role of microRNA-21 (miR-21) in colorectal cancer (CRC) and to elucidate the regulation of phosphatase and tensin homologue (PTEN) gene by miR-21. MiR-21 expression was investigated in 30 CRC samples and five CRC cell lines. In this study, we show that the expression of miR-21 was overexpressed in CRC compared with adenomas and normal tissues. Patients with poor differentiation, lymph node metastasis and advanced TNM stage showed significantly high expression of miR-21. Inhibition of miR-21 in the HCT116 cell line reduced cellular proliferation, migration and invasion, induced apoptosis and inhibited cell cycle progression. The PTEN protein levels in CRC tissues and cells had an inverse correlation with miR-21 expression. Anti-miR-21-transfected cells increased PTEN protein expression without changing the PTEN mRNA level and increased a luciferase-reporter activity. MiR-21 targets PTEN at the post-transcriptional level and regulates cell proliferation and invasion in CRC. It may serve as a novel therapeutic target in CRC.

Laparoscopic versus open total mesorectal excision for middle and low rectal cancer: a meta-analysis of results of randomized controlled trials.

BACKGROUND: Laparoscopic total mesorectal excision (LTME) for rectal cancer remains controversial. The aim of this meta-analysis of randomized controlled trials (RCTs) is to compare LTME and open total mesorectal excision (OTME) as the primary treatment for patients with middle and low rectal cancer with regard to short-term outcomes. MATERIALS AND METHODS: Literature searches of electronic databases (PubMed, Embase, and the Cochrane Library) and manual searches up to October 30, 2011 were performed. Prospective randomized clinical trials were eligible if they included patients with middle and low rectal cancer treated by LTME versus OTME. Fixed and random effects models were used. Review Manager version 5.1 software was used for pooled estimates. RESULTS: Four RCTs enrolling 624 participants (LTME group, 308 cases; OTME group, 316 cases) were included in the meta-analysis. LTME for rectal cancer was associated with a significantly longer operative time but significantly less intraoperative blood loss and earlier time to pass first flatus. We found no significant differences in the number of lymph nodes, overall morbidity, and perioperative mortality rates between the two groups. Time to resume liquid diet, time to resume normal diet, and length of hospital stay, although not significantly different between the two groups, did suggest a positive trend toward LTME. CONCLUSIONS: It may be concluded that LTME is a safe and effective alternative to OTME and is justifiable under the setting of clinical trials. Additional RCTs that compare LTME and OTME and investigate the long-term oncological outcomes of LTME are required to determine the advantages of LTME over OTME.