NSUN5-FTH1 Axis Inhibits Ferroptosis to Promote the Growth of Gastric Cancer Cells.

Recent studies revealed that NOP2/Sun RNA methyltransferase 5 (NSUN5) - ferritin heavy chain (FTH1) pathway is associated with ferroptosis in stem cells, whereas its roles in gastric cancer are still unclear. Our study aims to investigate the roles of the NSUN5-FTH1 axis in gastric cancer (GC) and its molecular mechanisms. Stable cell lines were constructed on SGC7901 cells by using shRNAs and pcDNA3.1 expression vectors, respectively. CCK-8 kits were used to determine cell viability. Biochemicals assays were used to detect lipid reactive oxygen species (ROS) and intracellular Fe2+ levels. RNA immunoprecipitation assay, qPCR, and Western blotting were used to determine the changes in biomarkers. GC xenograft mouse model was established to confirm the observation in vivo. An elevation of NSUN5 was observed in GC tumor tissues. NSUN5 inhibited ferroptosis including decreasing cell viability and increasing levels of lipid ROS and Fe2+ in GC cells. Besides, a positive correlation was also observed between NSUN5 and FTH1. Interestingly, NSUN5 regulated the levels of FTH1, instead of FTH1 regulating NSUN5 in GC cells. NSUN5-FTH1 axis regulated erastin-induced ferroptosis in SGC7901 cells. Consistently, silencing NSUN5 or FTH1 inhibited the growth of the SGC7901 tumor in vivo. NSUN5-FTH1 axis promoted the growth of GC cells in part by the regulation of ferroptosis.

Homoharringtonine Attenuates Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Signaling.

Homoharringtonine (HHT) exhibits an anti-inflammatory activity. The potential protective effects and mechanisms of HHT on dextran sulfate sodium- (DSS-) induced colitis were investigated. DSS-induced colitis mice were intraperitoneally injected with HHT. Body weight, colon length, disease activity index (DAI), and histopathological change were examined. The relative contents of interleukin- (IL-) 1ß, tumor necrosis factor- (TNF-) α, IL-6, and the chemokine (C-C motif) ligand 2 (CCL2) in the colon tissues and HHT-treated RAW264.7 cells were detected with the enzyme-linked immunosorbent assay. In the meantime, the levels of p-p65 and p-IκBα were detected by Western blot. The proportion of macrophages (CD11b+F4/80+) in the colon tissues was detected by flow cytometry. HHT alleviated DSS-induced colitis with downregulated TNF-α, IL-1ß, IL-6, and CCL2 expression; reduced activation of nuclear factor-kappa B (NF-κB) signaling; and diminished proportion of recruited macrophages in colon tissues. It was further testified that HHT inhibited lipopolysaccharide-induced macrophage activation with reduced activation of NF-κB signaling. In addition, HHT inhibited the M1 polarization of both human and mouse macrophages, while HHT did not affect the differentiation of human CD4 T cells into Th17, Th1, or Treg cells and did not affect the proliferation and migration of human colon epithelial cells. In summary, HHT attenuates DSS-induced colitis by inhibiting macrophage-associated NF-κB activation and M1 polarization, which could be an option for the treatment of ulcerative colitis.

miR-146b-5p promotes colorectal cancer progression by targeting TRAF6.

Increasing evidence highlights the multiple roles of microRNAs (miRs) in the tumorigenesis of colorectal cancer (CRC); however, the molecular mechanism, particularly the target of miR-146b-5p in CRC has not been fully elucidated. The present study aimed to elucidate the influence of miR-146b-5p via regulating tumor necrosis factor receptor-associated factor 6 (TRAF6) in CRC. The expression levels of miR-146b-5p and TRAF6 in CRC tissue and cells were determined by reverse transcription quantitative PCR and western blotting. Binding between miR-146b-5p and TRAF6 was examined using a dual luciferase reporter gene assay. The impact of miR-146b-5p and TRAF6 on proliferation and migration of CRC cells was determined using Cell Counting Kit-8 and Transwell assays, respectively. An animal model of CRC was established to determine the carcinogenic effect of the miR-146b-5p-TRAF6 axis. The results demonstrated that miR-146b-5p was highly expressed in CRC tissue samples compared with in normal adjacent tissue samples and in CRC cells compared with in the normal NCM460 cell line, whereas TRAF6 was expressed at low levels. Overexpression of miR-146b-5p decreased TRAF6 expression in CRC HT29 and SW620 cells. miR-146b-5p targeted and inhibited TRAF6 expression in CRC cells. Furthermore, transfection with a miR-146b-5p mimic promoted the proliferation, migration and invasion of CRC cells and tumor growth; however, these effects were abolished by TRAF6 overexpression. Transfection with a miR-146b-5p inhibitor suppressed the proliferation of CRC cells. Taken together, the results from the present study demonstrated that miR-146b-5p could enhance the initiation and tumorigenesis of CRC by targeting TRAF6. These results will help elucidate the mechanisms underlying CRC development and will facilitate the development of targeted therapy for CRC.

Early microsurgery on thoracolumbar spinal extradural arachnoid cysts: Analysis of a series of 41 patients.

BACKGROUND: We designed this study to share our management experiences on spinal extradural arachnoid cysts (SEACs) to add more to the body of evidence for their treatment. METHODS: We retrospectively reviewed 41 patients who underwent microsurgery for thoracolumbar SEACs at our hospital from June 2009 to June 2019. All clinical data, including medical history, clinical features, imaging manifestation, operative findings, and prognosis, were extracted from medical records and databases. Perioperative differences of the Visual Analogue Scale (VAS), the Oswestry disability index (ODI) score, and postoperative Odom's criteria were used to assess the surgical outcome. RESULTS: The most common and very first clinical symptom in the 41 patients was pain (VAS = 2.82 ± 0.89), and the mean ODI value was 61.7 ± 8.9%. Imaging revealed that the cystic lesions in the thoracolumbar spine involved an average of 2.85 segments. Of the 41 patients, 39 underwent total cyst excisions, and 36 had their dural defect repaired by one of three methods. The mean postoperative follow-up time was 52.3 months. Postoperatively, one case developed kyphoscoliosis and two cases experienced a recurrence. The majority of patients showed excellent outcomes according to Odom's criteria, the postoperative VAS (0.80 ± 1.08), and the ODI (15.4 ± 9.3%). CONCLUSIONS: Themost commonclinicalsymptoms of thoracolumbar SEACs included progressive discomfort and pain around the involved spinal segments. Early surgical intervention relieved the patients from their symptoms. Microsurgery was recommended to resect the complete cyst and to repair the dural defect, but resection of the complete cyst is more necessary than just repairment of the dural defect for providing promising outcomes.

Clinical analysis of metastatic characteristics of infrapyloric lymph nodes (No.206) and terminal ileum lymph nodes in patients with right colon cancer.

BACKGROUND: D3 or complete mesocolic excision (CME) surgery has become a common surgical procedure for the treatment of colon cancer metastasis. Clinical misuse and overuse of lymph node dissection bring unnecessary burdens to patients. A detailed guidance for lymph node dissection in patients with T3 and T4 stage right colon cancer at different locations is urgently needed. METHODS: A retrospective study was performed. Patients received D3 or CME surgery were divided into ileocecal group, ascending colon group, and hepatic flexure group according to the 9th edition of the Japanese Society for Cancer of the Colon and Rectum guidelines. The distributions of lymph node metastases were analyzed according to tumor infiltration depth (T stage) and tumor location. RESULTS: The incidence of metastases in the paracolic area (or station), intermediate area, and main (or central) area was 38.4% (139/362), 12.7% (46/362), and 9.7% (35/362), respectively. The proportion of patients having No.206 and terminal ileum lymph nodes metastases was 7.7% (14/181) and 3.7% (9/244), respectively. No.206 lymph node metastasis is related to tumor location (χ2 = 7.955, p = 0.019) and degree of differentiation (χ2 = 18.99, p = 0.000), and terminal ileum lymph node metastasis is related to tumor location (χ2 = 6.273, p = 0.043). Patients with T3/T4 hepatic flexure cancer received radical right hemicolectomy in addition to No.206 lymph node dissection. CONCLUSION: Radical right hemicolectomy and No.206 group lymph node dissection are necessary for T3 and T4 stage colon cancer therapy.

Worse prognosis in young patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy: A comparative study.

To determine the efficacy of neoadjuvant chemoradiotherapy (NCRT) between young and old patients with locally advanced rectal cancer (LARC) in terms of tumor response and survival outcome.LARC patients undergoing NCRT and radical surgery from 2011 to 2015 were included and divided into: young (aged ≤50 years) and old group (aged >50 years). Multivariate analyses were performed to identify risk factors for local recurrence. Least absolute shrinkage and selection operator analysis was performed to identify risk factors for overall survival. Predicting nomograms and time-indepent receiver operating characteristic curve analysis were performed to compare the models containing with/withour age groups.A total of 572 LARC patients were analyzed. The young group was associated with higher pathological TNM stage, poorly differentiated tumors, and higher rate of positive distal resection margin (P = .010; P = .019; P = .023 respectively). Young patients were associated with poorer 5-year disease-free survival and local recurrence rates (P = .023, P = .003 respectively). Cox regression analysis demonstrated that age ≤50 years (Hazard ratio = 2.994, P = .038) and higher pathological TNM stage (Hazard ratio = 3.261, P = .005) were significantly associated with increased risk for local recurrence. Least absolute shrinkage and selection operator analysis and the time-indepent receiver operating characteristic curve analysis demonstrated that including the age group were superior than that without age group.Young patients were associated with poorer disease free survival (DFS) and a higher risk for local recurrence in LARC following NCRT. The predicting model basing based on the age group had a better predictive ability. More intense adjuvant treatment could be considered to improve DFS and local control for young patients with LARC following NCRT.

Laparoscopic Surgery Versus Open Surgery for Colorectal Cancer: Impacts on Natural Killer Cells.

Background: Laparoscopic resection is increasingly used in colorectal cancer (CRC). It has been suggested to carry short-term benefits in safety, recovery, and preservation on immune function for patients with CRC. However, the impact of laparoscopic resection on natural killer (NK) cells is largely unclear. METHODS: A total of 200 patients with CRC across Dukes A/B/C stages were randomly assigned to laparoscopic or open resection. The blood samples were collected before and after the surgery. The total number of NK cells was quantified by flow cytometer. Lytic units 35 toward K562 was used to quantify NK cells activity. The outcomes between the groups across pathological stages were also analyzed. RESULTS: The number and activity of NK cells decreased after the surgery in both groups. The laparoscopic group showed a faster recovery rate of NK cells function than the control group as assessed by cell count and lytic activity. Natural killer cells were impaired in a higher degree in patients at Dukes B/C stages. The recovery of NK cells to baseline level at day 7 postsurgery was observed in the laparoscopic group across all 3 stages. CONCLUSION: Generally, laparoscopically assisted surgery resulted in a better preservation on NK cells function. A better outcome was observed in patients with CRC at Dukes B/C stages.

MicroRNA-149 sensitizes colorectal cancer to radiotherapy by downregulating human epididymis protein 4.

Human epididymis protein 4 (HE4) was significantly up-regulated in colorectal cancer (CRC), while the potential relevance to radiation resistance of this phenomenon is still elusive. Relative expressions of target genes were quantified by real-time PCR. The protein level was determined by Western blot. The regulatory effect of miR-149 on WFDC2 (gene encoding HE4 protein) expression was analyzed by luciferase reporter assay. The response to radiation was evaluated by clonogenic assay in vitro and xenograft growth in vivo. WFDC2 was aberrantly up-regulated and miR-149 was down-regulated in CRC. MiR-149 repressed WFDC2 expression via directly targeting its 3'UTR region. The ectopic expression of miR-149 significantly sensitized CRC to radiation both in vitro and in vivo. Likewise, we further demonstrated that WFDC2-deficiency remarkably improved the radiation resistance in CRC. Simultaneously, WFDC2 rescue completely abolished the radiation sensitivity imposed by miR-149. Our data suggested that miR-149 sensitized CRC to radiation via directly inhibiting WFDC2/HE4, which would hold great promise for future therapeutic exploitations.

Triterpenes and steroids from the roots of Scorzonera austriaca.

A new D:B-friedoolean-type triterpene, 3ß-acetoxyglutin-5(10)-en-6-oxo (1), together with seventeen known compounds (2-18) was isolated from the roots of Scorzonera austriaca. Their structures were elucidated mainly by NMR and HR-ESI-MS, as well as on comparison with the reported data. Cytotoxicities of compounds 2, 4, 6, 10-14 and 16 against selected cancer cells of human promyelocytic leukemia (HL-60) and human hepatoma (BEL-7404) were measured in vitro.

Heavy metal pollution in tidal zones of Bohai Bay using the dated sediment cores.

Three sediment cores were collected in November 2003 from Dagu estuary to Qikou estuary. The main polluted heavy metals in the sediment of tidal zones for the Bohai Bay have been found by analyzing the relationship among the contents of heavy metals, the contents of geochemical elements (Fe, Al and Mn) and the size of grain. The dominating contaminative elements in tidal sediments of Bohai Bay are Pb, Zn and Cd. Their contents are higher than the corresponding upper limit of environmental background values and they have very faint correlation with the corresponding contents of geochemical elements and the size of grain, indicating the anthropogenic enrichment. Especially, the preliminary study on the pollution sources and the history of heavy metals in the Dagu estuary has been done using the dated results. The contamination by Zn and Cd also started in the middle 1950s, while the contamination by Pb appeared in the early 1940s. The pollution by Zn and Cd mainly originate from sewage discharge, while the pollution by Pb has many sources, like atmosphere deposition and industrial discharge.