Cell fusion plays a crucial role in cancer progression and leads to massive aberrant changes in chromosome and gene expression involved in tumor metastasis. Cancer cells can fuse with many cell ...types, including stromal cells, epithelial cells, macrophages, and endothelial cells. Mesenchymal stem cells (MSCs) have been reported to migrate and incorporate into tumor sites during cancer progression. However, the underlying mechanism of stem cell fusion in tumor metastasis has not been fully deciphered. In this research, we established a cell fusion model between lung cancer cells and MSCs in vitro. We found that the hybrid cells showed enhanced metastatic capacity with increased expression of MMP‐2 and MMP‐9, whereas the proliferation ability was inhibited and cell cycle was blocked in the G0/G1 phase with elevated expression of p21, p27, and p53. Moreover, the hybrid cells lost epithelial morphology and exhibited an epithelial‐mesenchymal transition (EMT) change with downregulation of E‐cadherin and upregulation of N‐cadherin, Vimentin, α‐SMA and Fibronectin1. Meanwhile, the expressions of EMT transcription factors, including Snail1, Slug, Twist1, Zeb1, and Zeb2, were also increased in hybrid cells. More important, the fusion hybrids acquired stem cell‐like properties, which exhibited increased expression stem cell transcription factors Oct4, Sox2, Nanog, Kif4 as well as Bmi1. Taken together, our results suggested that cell fusion between lung cancer cells and MSCs offered enhanced metastatic capacity and characteristics of cancer stem cell by undergoing EMT. This study will contribute to explaning the origin of lung cancer stem cells and to elucidate the role of cell fusion in cancer metastasis.
We have demonstrated that fusion hybrids between lung cancer cells and MSCs offer enhanced metastatic abilities and cancer stem cell‐like properties by inducing epithelial‐mesenchymal transition (EMT). Our findings suggested that stem cell fusion would provide a new explanation for the origin of cancer stem cells and has an important consequence on lung cancer therapy.
•Efficient methods for deproteinizing and decolorizing polysaccharides demonstrated.•Polyamide chromatography is the most efficient deproteinization method.•Resin S-8 is the most efficient ...decolorization method.•Salt-eluted polysaccharide has more significant immunostimulatory effects.•Polysaccharide fraction SPS-3 showed the most immunostimulatory activity.
In this study, crude American ginseng polysaccharide (AGPS) was extracted with hot water and preliminarily purified by using resin S-8 and Polyamide columns. Then, it was further purified and separated by DEAE-Sepharose CL-6B and Sepharose CL-6B chromatography, respectively. Five main fractions were obtained, named WPS-1, WPS-2, SPS-1, SPS-2 and SPS-3. Their homogeneities and structural characteristics were elucidated based on UV–vis spectroscopy, High Performance Gel Filtration Chromatography (HPGFC), Gas Chromatography (GC), Scanning Electron Microscopy (SEM), Infrared Spectrum (IR), and NMR Spectroscopy methods. Furthermore, the immunostimulatory effects of these fractions upon splenic lymphocyte proliferation, macrophage phagocytosis and nitric oxide (NO) production, were investigated in vitro. The results indicated that their stimulations could be ordered as SPS-3>SPS-1>CPS (crude polysaccharides)>WPS-1>WPS-2>SPS-2. Among them, SPS-3 showed more potent immunomodulatory activity and could be explored as a potential immunopotentiating agent for use in functional food or medicine.
Cdc42, a member of the Rho GTPases family, is involved in the regulation of several cellular functions including cell cycle progression, survival, transcription, actin cytoskeleton organization and ...membrane trafficking. Diabetes is a chronic and metabolic disease, characterized as glycometabolism disorder induced by insulin deficiency related to β cell dysfunction and peripheral insulin resistance (IR). Diabetes could cause many complications including diabetic nephropathy (DN), diabetic retinopathy and diabetic foot. Furthermore, hyperglycemia can promote tumor progression and increase the risk of malignant cancers. In this review, we summarized the regulation of Cdc42 in insulin secretion and diabetes-associated diseases. Organized researches indicate that Cdc42 is a crucial member during the progression of diabetes, and Cdc42 not only participates in the process of insulin synthesis but also regulates the insulin granule mobilization and cell membrane exocytosis via activating a series of downstream factors. Besides, several studies have demonstrated Cdc42 as participating in the pathogenesis of IR and DN and even contributing to promote cancer cell proliferation, survival, invasion, migration, and metastasis under hyperglycemia. Through the current review, we hope to cast light on the mechanism of Cdc42 in diabetes and associated diseases and provide new ideas for clinical diagnosis, treatment, and prevention.
As a highly heterogeneous malignancy, breast cancer (BC) has become the most significant threat to female health. Distant metastasis and therapy resistance of BC are responsible for most of the cases ...of mortality and recurrence. Distant metastasis relies on an array of processes, such as cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis. Long non-coding RNA (lncRNA) refers to a class of non-coding RNA with a length of over 200 nucleotides. Currently, a rising number of studies have managed to investigate the association between BC and lncRNA. In this study, we summarized how lncRNA has dual effects in BC metastasis by regulating invasion, migration, and distant metastasis of BC cells. We also emphasize that lncRNA has crucial regulatory effects in the stemness and angiogenesis of BC. Clinically, some lncRNAs can regulate chemotherapy sensitivity in BC patients and may function as novel biomarkers to diagnose or predict prognosis for BC patients. The exact impact on clinical relevance deserves further study. This review can be an approach to understanding the dual effects of lncRNAs in BC, thereby linking lncRNAs to quasi-personalized treatment in the future.
In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children.
Data were collected from 72 children with ...multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested.
The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery.
Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.
Lung cancer is the main cause of cancer-related mortality worldwide. We report here the biological role of nuclear paraspeckle assembly transcript 1 (NEAT1) in the pathogenesis of lung cancer and the ...underlying mechanisms.
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis were used to evaluate expression of mRNA and protein. RNA immunoprecipitation (RIP) assay, chromatin immunoprecipitation followed by qPCR analysis, and reporter assay were used to detect DNA/RNA and protein binding. Tumor-infiltrating lymphocytes were assessed with hematoxylin-eosin staining. Cytotoxic T cell infiltration was evaluated with flow cytometric analysis and immunohistochemistry (IHC) staining. The changes of cell viability and cell invasive and migratory ability were analyzed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, and Transwell assays, respectively. Syngeneic tumor model was set up to evaluate antitumor effect.
The results showed that NEAT1 was overexpressed in lung cancer tissues and cancer cell lines. This aberrant expression was closely related with tumor stage and lymph node metastasis. Tumor sample with high CD8
showed lower NEAT1 expression.
studies displayed that inhibition of NEAT1 with shRNA resulted in suppression of survival and migration/invasion of lung cancer cells. On the other side, NEAT1 was found to promote tumor growth via inhibiting cytotoxic T cell immunity in syngeneic models. Finally, NEAT1 was found to interact with DNMT1, which in turn inhibited P53 and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS/STING) expression.
Our findings demonstrated that NEAT1 interacted with DNMT1 to regulate cytotoxic T cell infiltration in lung cancer via inhibition of cGAS/STING pathway. The results provided the novel mechanistic insight into the pathogenesis of lung cancer.
The quality and quantity of mulberry leaves are often affected by various environmental factors. The plant NPR1 and its homologous genes are important for plant systemic acquired resistance. Here, ...the full‐length cDNAs encoding the NPR1 and NPR4 genes (designated MuNPR1 and MuNPR4, respectively) were isolated from Morus multicaulis. Sequence analysis of the amino acids and protein modeling of the MuNPR1 and MuNPR4 proteins showed that MuNPR1 shares some conserved characteristics with its homolog MuNPR4. MuNPR1 was shown to have different expression patterns than MuNPR4 in mulberry plants. Interestingly, MuNPR1 or MuNPR4 transgenic Arabidopsis produced an early flowering phenotype, and the expression of the pathogenesis‐related 1a gene was promoted in MuNPR1 transgenic Arabidopsis. The MuNPR1 transgenic plants showed more resistance to Pseudomonas syringae pv. tomato DC3000 (Pst. DC3000) than did the wild‐type Arabidopsis. Moreover, the ectopic expression of MuNPR1 might lead to enhanced scavenging ability and suppress collase accumulation. In contrast, the MuNPR4 transgenic Arabidopsis were hypersensitive to Pst. DC3000 infection. In addition, transgenic Arabidopsis with the ectopic expression of either MuNPR1 or MuNPR4 showed sensitivity to salt and drought stresses. Our data suggest that both the MuNPR1 and MuNPR4 genes play a role in the coordination between signaling pathways, and the information provided here enables the in‐depth functional analysis of the MuNPR1 and MuNPR4 genes and may promote mulberry resistance breeding in the future.
In individuals with underlying chronic liver disease (CLD), hepatitis E virus (HEV) infection is a potential trigger of acute‐on‐chronic liver failure. In this systematic review, seven electronic ...databases were searched. Pooled incidence rates with 95% confidence intervals (95% CIs) were calculated by the Freeman–Tukey double arcsine transformation method. The association between death or liver failure and HEV superinfection in CLD patients was estimated by the odds ratios (OR) with a 95% CI. A total of 18 studies from 5 countries were eligible for systematic review. The prevalence of acute HEV infection in hospitalized CLD patients with clinical manifestations of hepatitis was 13.6%, which was significantly higher than that in CLD patients from the community (pooled prevalence 1.1%). The overall rates of liver failure and mortality in CLD patients with HEV superinfection were 35.8% (95% CI: 26.7%–45.6%) and 14.3% (95% CI: 10.6%–18.5%), respectively, with the rates in cirrhotic patients being approximately 2‐fold and 4‐fold higher than those in noncirrhotic patients, respectively. The risks of liver failure (OR = 5.5, 95% CI: 1.5–20.1) and mortality (OR = 5.0, 95% CI: 1.9–13.3) were significantly higher in CLD patients with HEV superinfection than in those without HEV superinfection. HEV testing in hospitalized CLD patients is necessary due to the high prevalence of HEV infection observed in hospitalized CLD patients. HEV superinfection could accelerate disease progression in patients with underlying CLD and increase mortality in these patients. HEV vaccination is appropriate for patients with pre‐existing CLD.
A taxonomic study was carried out on strain BGMRC 0090
, which was isolated from seawater. The isolate was a Gram-negative, aerobic, flagellated, rod-shaped bacterium with algicidal activity. Optimal ...growth was observed at 30 °C, pH 6.0 and with 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain BGMRC 0090
belonged to the genus
, with highest sequence similarity to
CC-MMS-1
(98.4 %). Average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values between strain BGMRC 0090
and five strains of the genus
with publicly available genomes were below 84.0, 69.2 and 21.4 %, respectively. The genome of strain BGMRC 0090
was 3.2 Mb with 64.8 mol% DNA G+C content and encoded 2905 predicted proteins, three rRNA, 42 tRNA and four ncRNA genes. Some algicidal biosynthesis-associated genes were detected in the genome. Strain BGMRC 0090
contained Q-10 as the major quinone. The predominant fatty acids were identified as summed feature 8 (C
ω7
/ω6
) and C
. Based on the polyphasic evidence presented in this paper, strain BGMRC 0090
is concluded to represent a novel species of the genus
, for which the name
sp. nov. is proposed. The type strain is BGMRC 0090
(= KCTC 92591
=MCCC 1K08100
).
Bundle recommendation aims to recommend a bundle of items for the user to purchase together, for which two scenarios (i.e., Next-bundle recommendation and Within-bundle recommendation) are explored ...to recommend a specific bundle of items for the user and a specific item to fill the user's current bundle, respectively. Previous works largely model the user's preference with a uniform intent, without considering the diversity of intents when adopting the items within the bundle. In the real scenario of bundle recommendation, user intents modeling actually needs to be considered from three hierarchical levels, for that: a user's intents may be naturally distributed in different bundles (user level), one bundle may contain multiple intents of a user (bundle level), and an item in different bundles may also present different user intents (item level). To this end, we develop a novel model, H ierarchical I ntent D isentangle G raph N etworks (HIDGN) for bundle recommendation. HIDGN is capable of capturing the diversity of the user's intent precisely and comprehensively from the hierarchical structure with an cross-task intent contrastive learning, which is unified with the supervised next-/within-bundle recommendation sub-tasks as a multi-task framework. Extensive experiments on three benchmark datasets demonstrate that HIDGN outperforms the state-of-the-art methods by 43.0<inline-formula><tex-math notation="LaTeX">\%</tex-math> <mml:math><mml:mo>%</mml:mo></mml:math><inline-graphic xlink:href="wei-ieq1-3329175.gif"/> </inline-formula>, 13.2<inline-formula><tex-math notation="LaTeX">\%</tex-math> <mml:math><mml:mo>%</mml:mo></mml:math><inline-graphic xlink:href="wei-ieq2-3329175.gif"/> </inline-formula>, and 73.3<inline-formula><tex-math notation="LaTeX">\%</tex-math> <mml:math><mml:mo>%</mml:mo></mml:math><inline-graphic xlink:href="wei-ieq3-3329175.gif"/> </inline-formula>, respectively.
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