Tofacitinib alleviated salivary gland inflammation and reduced the percentages of effector T cells in murine Sjögren's disease.

OBJECTIVES: The Janus kinases-signal transducer and activator of transcription (JAK-STAT) signalling pathway plays a crucial role in autoimmunity and the signalling pathways of many cytokines in Sjögren's disease (SjD). Therefore, the aim of this study was to investigate both the therapeutic and immunomodulatory effects of the oral JAK3/JAK2/JAK1 inhibitor tofacitinib in a murine model of SjD. METHODS: Tofacitinib or vehicle was administered orally to the mice with SjD for 6 weeks. Salivary flow rate was measured every three weeks. Pathological changes of salivary gland were detected by haematoxylin-eosin staining, and the percentages of subsets of CD4+ T cells and B cells in the cervical lymph nodes (cLNs) and spleen was determined by flow cytometry. RESULTS: Tofacitinib significantly ameliorated submandibular gland inflammation compared to the control group, as evidenced by reduced lymphocytic infiltration. Salivary flow rates improved significantly in tofacitinib treated mice compared to controls, indicating restored salivary gland function. The treatment also led to a substantial decrease in follicular helper T (Tfh) cells and the Tfh/Treg ratio in both the spleen and cLNs. Additionally, the frequencies of T helper 1 (Th1) and T helper 17 (Th17) cells were reduced in the spleen and cLNs. CONCLUSIONS: Our data indicated that tofacitinib reduced percentages of effector T cells in an animal model of SjD. In addition, tofacitinib alleviated salivary gland inflammation and hypofunction, offering new insights into the clinical management of SjD.

Clinical features and prognostic biomarkers in patients with SMARCA4-mutated non-small cell lung cancer.

Background: Patients with non-small cell lung cancer (NSCLC) carrying SMARCA4 mutations (SMARCA4-Mut) tend to have more advanced disease and a poor prognosis. However, due to the rarity of this mutation and the lack of related studies, the characteristics of SMARCA4-Mut NSCLC patients remains poorly determined. To clarify the clinical characteristics and prognostic factors of SMARCA4-Mut NSCLC, we initiated the present study to provide a clinical reference. Methods: We used data from two cohorts of NSCLC-SMARCA4-mutated samples: The Cancer Genome Atlas (TCGA) database and our center's clinical data. The TCGA database was used to obtain 481 NSCLC-SMARCA4-Mut samples for clinical characterization. The center collected data on 224 consecutive NSCLC patients treated between December 2020 to July 2022. Among them, 26 harbored SMARCA4 mutations, and 20 were eligible for inclusion in the study. Clinical, pathological, and molecular features, as well as prognostic role of SMARCA4 mutations were analyzed. Additionally, we analyzed the prognostic impact of Napsin A expression in SMARCA4-Mut patients. Results: The TCGA database included 480 patients with SMARCA4-Mut NSCLC, 311 males (64.8%) and 169 females (35.2%), with a median age of 67 years. Among the 20 SMARCA4-Mut patients in our center series, 12 (60%) were males and 8 (40%) females, with a median age of 63. The intergroup prognostic correlation analysis showed that SMARCA4-Mut patients had significantly worse prognosis than those the wild-type SMARCA4 (SMARCA4-WT) (P=0.04). Within the SMARCA4-Mut group, patients with Napsin A expression had longer overall survival (OS) (P=0.03) than those without expression. Median survival in the Napsin A-positive and negative groups was 32 and 15 months, respectively. According to time-dependent receiver operating curve analysis, patients with Napsin A expression had significantly longer first-line treatment progression-free survival (PFS1) [area under the curve (AUC) =0.748] and OS (AUC =0.586). No prognostic value of Napsin A was found in patients SMARCA4-WT patients. Conclusions: SMARCA4-Mut is an adverse prognostic feature in NSCLC patients. Napsin A expression in SMARCA4-Mut patients is associated with prolonged OS.

An immunogenic cell death-related lncRNA signature correlates with prognosis and tumor immune microenvironment in bladder cancer.

Immunogenic cell death (ICD) is a newly discovered form of cellular demise that triggers adaptive immune responses mediated by T cells. However, the immunogenic cell death-related lncRNAs (ICDRLs) involved in bladder cancer (BC) development and progression remain to be further elucidated. Molecular profiling data and clinicopathological information for BC patients were obtained from TCGA, and the ICDRGs list was obtained from published literature. For the identification of ICDRLs, Pearson co-expression analysis was performed, and a prognostic signature based on 13 ICDRLs was constructed by univariate assays and LASSO assays. Herein, an ICDRLSig consisting of 13 ICDRLs was constructed. KM curves and ROC curves demonstrated that the constructed signature in the TCGA training, testing, entire and external sets have good predictive performance. Multivariate assays illuminated that the signature is an independent predictor for BC patients' OS, exhibiting greater predictive power for the survival than traditional clinicopathological features. Additionally, patients in the high-ICDRLSig risk subgroup had more abundant immune infiltration, higher immune checkpoint gene expression, lower TMB and poorer response to immunotherapy. We have developed a novel ICDRLSig that can be exploited for survival prediction and provide a reference for further individualized treatment.

Effect and mechanism of coexistence of microplastics on arsenate adsorption capacity in water.

Arsenic pollution control technology in water was important to ensure environmental health and quality safety of agricultural products. Therefore, the adsorption performance of three adsorbents for chitosan, sepiolite, and Zeolitic Imidazolate Framework-8 (ZIF-8) were investigated in arsenate contaminated water. The results revealed that the adsorption capacity of ZIF-8 was higher than that of chitosan and sepiolite. The analysis of adsorption isotherm models showed that the behavior of ZIF-8 was more consistent with the Langmuir model. Furthermore, the adsorption mechanisms of three adsorbents for arsenate were investigated by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The analysis of FTIR showed that ZIF-8 maintained the stability of the interaction with arsenate by forming As-O chemical bonds. However, the effect of chitosan and sepiolite with arsenate was mainly physical adsorption. The analysis of XPS showed that the absorption of ZIF-8 with arsenate involved metal sites and nitrogen through the characteristic peak and the change of the binding energy. Furthermore, the impact of microplastics as a widespread coexistence pollutant in the water on adsorbent performance was investigated. The results indicated that the adsorption capacity of ZIF-8 was almost not affected by microplastics. The maximum adsorption amount of arsenate was changed from 73.45 mg/g to 81.89 mg/g. However, the maximum adsorption amount of chitosan and sepiolite decreased by 31.4 % and 11.6 %, respectively. The analysis of FTIR and XPS revealed that ZIF-8 enhances arsenate adsorption by forming N-O-As bonds in the presence of microplastics. This study provides scientific evidence for the management of arsenate pollution in water bodies, especially in complex water bodies containing microplastics.

Temporal dynamics of lignin degradation in Quercus acutissima sawdust during Ganoderma lucidum cultivation.

Despite a fair amount of lignin conversion during mycelial growth, previous structural analyses have not yet revealed how lignin changes continuously and what the relationship is between lignin and ligninolytic enzymes. To clarify these aspects, Quercus acutissima sawdust attaching Ganoderma lucidum mycelium collected from different growth stage was subjected to analysis of lignin structure and ligninolytic enzyme activity. Two key periods of lignin degradation are found during the cultivation of G. lucidum: hypha rapid growth period and primordium formation period. In the first stage, laccase activity is associated with the opening of structures such as methoxyls, ß-O-4' substructures and guaiacyl units in lignin, as well as the shortening of lignin chains. Manganese peroxidases and lignin peroxidases are more suitable for degrading short chain lignin. The structure of phenylcoumarans and syringyl changes greatly in the second stage. The results from sawdust attaching mycelium provide new insights to help improve the cultivation substrate formulation of G. lucidum and understand biomass valorization better.

Podocyte-specific Nup160 knockout mice develop nephrotic syndrome and glomerulosclerosis.

More than 60 monogenic genes mutated in steroid-resistant nephrotic syndrome (SRNS) have been identified. Our previous study found that mutations in nucleoporin 160 kD (NUP160) are implicated in SRNS. The NUP160 gene encodes a component of the nuclear pore complex. Recently, two siblings with homozygous NUP160 mutations presented with SRNS and a nervous system disorder. However, replication of nephrotic syndrome (NS)-associated phenotypes in a mammalian model following loss of Nup160 is needed to prove that NUP160 mutations cause SRNS. Here, we generated a podocyte-specific Nup160 knockout (Nup160podKO) mouse model using CRISPR/Cas9 and Cre/loxP technologies. We investigated NS-associated phenotypes in these Nup160podKO mice. We verified efficient abrogation of Nup160 in Nup160podKO mice at both the DNA and protein levels. We showed that Nup160podKO mice develop typical signs of NS. Nup160podKO mice exhibited progression of proteinuria to average albumin/creatinine ratio (ACR) levels of 15.06 ± 2.71 mg/mg at 26 weeks, and had lower serum albumin levels of 13.13 ± 1.34 g/l at 30 weeks. Littermate control mice had urinary ACR mean values of 0.03 mg/mg and serum albumin values of 22.89 ± 0.34 g/l at the corresponding ages. Further, Nup160podKO mice exhibited glomerulosclerosis compared with littermate control mice. Podocyte-specific Nup160 knockout in mice led to NS and glomerulosclerosis. Thus, our findings strongly support that mutations in NUP160 cause SRNS. The newly generated Nup160podKO mice are a reliable mammalian model for future study of the pathogenesis of NUP160-associated SRNS.

Microvascular invasion is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma.

OBJECTIVES: Microvascular invasion (MVI) has previously been reported to be related to cancer prognosis; however, its significance in patients with dual-phenotype hepatocellular carcinoma (DPHCC) remains uncharacterized. We studied the role of MVI in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of HCC. METHODS: Patients with DPHCC (n = 84) who had undergone surgical interventions at the 900th Hospital of the Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between MVI and patient survival. RESULTS: Our results indicated that MVI was related to poor survival. According to the univariate analysis, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, the expression of cytokeratin 19 (CK19), and serum levels of both ɑ-fetoprotein (AFP) and cancer antigen-199 showed a strong correlation with overall survival. Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Tumor size; the number of tumor lesions; differentiation; peripheral hepatic fibrosis; liver capsule invasion; and expression of CK19, vascular endothelial growth factor, CK7, and mucin 1 showed a correlation with MVI, per the outcomes of χ2 tests. CONCLUSIONS: Microvascular invasion may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Measurement Method of Physical Parameters of Two-Phase Flow Based on Dual-Frequency Demodulation.

Oil-water two-phase flow commonly occurs in the process of crude oil electric dehydration. Here, through dynamic changes in the water content and conductivity of oil-water two-phase flow in the process of electric dehydration, the influence of water content and conductivity on the efficiency and stability of electric dehydration is analyzed. Using real-time in-line measurements of water content and conductivity, the electric dehydration system is kept in an optimal state, which provides a basis for realizing efficient oil-water separation. Measurements of the physical parameters of oil-water two-phase flow is affected by many factors, such as the temperature of the two-phase flow, composition of the two-phase flow medium, structure of the measurement sensor, coupling of the conventional resistance-capacitance excitation signal, and processing of the measurement data. This complexity causes, some shortcomings to the control system, such as a large measurement error, limited measurement range, inability to measure the medium water phase as a conductive water phase, etc., and not meeting the requirements of the electric dehydration process. To solve that the conductivity and water content of high-conductivity crude oil emulsions cannot be measured synchronously, the RC relationship of oil-water emulsions is measured synchronously using dual-frequency digital demodulation technology, which verifies the feasibility of our test method for the synchronous measurement of physical parameters of homogeneous oil-water two-phase flow. Experimental results show that the novel measuring method (which is within the target measuring range) can be used to measure water content 0~40% and conductivity 1 ms/m~100 ms/m. The measuring error of the water content is less than 2%, and the measuring error of the conductivity is less than 5%.

Ligand-Directed Photodegradation of Interacting Proteins: Oxidative HER2/HER3 Heterodimer Degradation with a Lapatinib-Derived Photosensitizer.

In this work, we described a photocatalytic approach, termed ligand-directed photodegradation of interacting proteins (LDPIP), for efficient protein-protein heterodimer degradation. This LDPIP approach utilizes a combination of a photosensitizing protein ligand and appropriate light and molecular oxygen to induce oxidative damage to the ligand-binding protein as well as its interacting protein partner. As a showcase study, a photosensitizing HER2 ligand HER-PS-I was rationally designed based on the FDA-approved HER2 inhibitor lapatinib to efficiently degrade HER2 together with its interacting protein partner HER3, which is thought to induce HER2-targeted therapy resistance and difficult to target by small molecules. HER-PS-I exhibited excellent anticancer activity against drug-resistant MDA-MB-453 cells and its three-dimensional multicellular spheroids. We hope that this LDPIP approach would find more applications in degrading proteins that are thought undruggable or difficult to drug.

Cauliflower-shaped Pleurotus ostreatus cultivated in an atmosphere with high environmental carbon dioxide concentration.

Commercial aspects, physiological properties, and nutritional characteristics of Pleurotus ostreatus grown under various environmental carbon dioxide concentration ([CO2]e) conditions were assessed. As [CO2]e increased, the activity of antioxidant enzymes (catalase, peroxidase, and superoxide dismutase) in fruiting body increased, activities of succinate dehydrogenase and cytochrome c oxidase were inhibited, and malondialdehyde and adenosine triphosphate (ATP) syntheses were reduced, leading to incomplete development of pilei and stipes, or even absence of pilei. Under high [CO2]e (≥1.00%), fruiting body of P. ostreatus was morphologically altered to assume cauliflower shape. This cultivation condition resulted in high total contents of crude protein, crude fiber, and amino acids, increased levels of umami- and sweet-tasting amino acids, and reduced levels of bitter-tasting amino acids, thus enhancing the flavor of the product. In conclusion, a novel "cauliflower-shaped" mushroom (P. ostreatus) was successfully cultivated at high (≥1.00%) environmental CO2 concentration. The product has a delicious taste and high nutritional value, is relatively easy to transport and store, and has excellent potential for commercial development.

Dynamics of T follicular helper cells in patients with rheumatic diseases and subsequent antibody responses in a three-dose immunization regimen of CoronaVac.

Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.

Related Factor Analysis and Nursing Strategies of Diarrhea in Critically Ill Patients with Enteral Nutrition.

Objective: To explore the related factors of diarrhea in critically ill patients with enteral nutrition (EN) in the intensive care unit (ICU). Methods: This single-center retrospective study analyzed the occurrence of intolerant diarrhea in ICU patients receiving EN treatment in our hospital. By collecting clinical data, univariate and multivariate logistic regression analysis was used to screen the risk factors for diarrhea. Results: Among 120 patients included in the study, 68 (48.33%) had diarrhea. Age (OR = 2.599, P = 0.027), use of antibiotics (OR = 3.496, P = 0.007), ICU hospitalization time (OR = 1.311, P = 0.001), and mechanical ventilation time (OR = 1.273, P = 0.035) were all independent risk factors for diarrhea in EN. Conclusion: Older age, frequent use of antibiotics, long ICU stay, and mechanical ventilation time can lead to diarrhea in ICU patients receiving EN treatment. It is necessary to effectively analyze the above independent factors and implement targeted interventions to improve the incidence of diarrhea in patients.

A Novel Polysaccharide From Heimioporus retisporus Displays Hypoglycemic Activity in a Diabetic Mouse Model.

A novel polysaccharide, Heimioporus retisporus Polysaccharide (HRP) was extracted from the edible mushroom Heimioporus retisporus. HRP had weight-average molecular weight 1,949 kDa and number-average molecular weight 873 kDa, and its major components were arabinose (0.71%), galactose (12.93%), glucose (49.00%), xylose (8.59%), mannose (17.78%), and glucuronic acid (10.99%). Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy revealed that HRP was composed of 1,3-linked ß-D-glucose, 1,6-linked ß-D-mannose, 1,6-linked ß-D-galactose, 1,4-linked ß-D-galactose, 1,4-linked ß-D-xylose, and 1,5-linked α-L-arabinose. Thermogravimetric analysis indicated that degradation temperature (T0) of HRP was 200°C. In an STZ-induced diabetic mouse model, oral administration of HRP (40 mg/kg/d) for 28 days significantly reduced blood glucose levels, and reduced heart organ index by decreasing expression of IL-6 and TNF-α. Our findings indicate hypoglycemic effect of HRP, and its potential application as a hypoglycemic agent.

PLGA microspheres carrying miR-20a-5p improved intestinal epithelial barrier function in patients with Crohn's disease through STAT3-mediated inhibition of Th17 differentiation.

BACKGROUND: Recent studies have shown that microRNAs (miRNAs) are aberrantly expressed in patients with Crohn's disease (CD). This suggests that the aberrant expression of miRNAs may contribute to the development of CD. Currently, the specific miRNAs involved in CD development have not been clearly identified. Therefore, we aimed to identify CD-associated miRNAs and explore their functions. METHODS: miRNA microarray analysis was performed to screen for differentially expressed miRNAs in colon tissues from normal controls (NC) and CD patients. The identified miRNAs were validated using quantitative real-time PCR (qPCR). The therapeutic roles of miR-20a-5p mimics via the delivery of poly(lactic-co-glycolic acid) microspheres (PLGA MSs) were further investigated in IL-10-/- mice with spontaneous chronic colitis that were used as a model of CD. The target genes of miR-20a-5p and the associated signaling pathways were identified through bioinformatic analysis and experimental verification of the interactions between the targets predicted by the algorithms and dysregulated mRNAs. RESULTS: The analysis showed that miR-20a-5p was the most significantly downregulated miRNA in patients with CD. Treatment with PLGA MSs carrying miR-20a-5p significantly ameliorated the colitis, decreased mucosal inflammation, and improved epithelial barrier function. Bioinformatic analysis and experimental studies showed that miR-20a-5p inhibition enhanced Th17 differentiation and improved intestinal epithelial barrier function by targeting STAT3. CONCLUSIONS: Downregulation of miR-20a-5p improved the intestinal epithelial barrier function and prevented CD development through the STAT3/IL-17 signaling pathway. Therefore, the delivery of miR-20a-5p by PLGA MSs may serve as a potential therapeutic strategy for CD treatment.

Neutral Polysaccharides From Hohenbuehelia serotina With Hypoglycemic Effects in a Type 2 Diabetic Mouse Model.

Neutral polysaccharides (NHSPs) from the mushroom Hohenbuehelia serotina were purified by D301/D152 resin ion-exchange chromatography and DEAE-cellulose anion exchange chromatography. The weight-average molecular weight (MW) and number-average molecular weight (Mn) of NHSP were 1,821 and 820.55 kDa, respectively. A monosaccharide component analysis showed that NHSP was composed of glucose, galactose, and mannose in molar ratio 2.6:2.1:1.0. FT-IR and NMR (1H and HSQC) spectroscopic analyses revealed that NHSP contained mainly 1,3-linked ß-D-glucose, 1,4-linked ß-D-glucose, 1,6-linked ß-D-mannose, 1,6-linked α-D-mannose, and 1,6-linked ß-D-galactose. The thermogravimetric analysis (TGA) showed that NHSP has good thermal stability below 250°C. NHSP notably reduced the blood glucose level (hypoglycemic effect) at dose 200 mg/kg for 21 days in a type 2 diabetic mouse model. NHSP reduced the liver index significantly, suggesting that it may help prevent hepatic steatosis or hepatomegaly.

A novel rat model for cerebral venous sinus thrombosis: verification of similarity to human disease via clinical analysis and experimental validation.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare neurovascular disorder with highly variable manifestations and clinical courses. Animal models properly matched to the clinical form of CVST are necessary for elucidating the pathophysiology of the disease. In this study, we aimed to establish a rat model that accurately recapitulates the clinical features of CVST in human patients. METHODS: This study consisted of a clinical analysis and animal experiments. Clinical data for two centres obtained between January 2016 and May 2021 were collected and analysed retrospectively. In addition, a Sprague-Dawley rat model of CVST was established by inserting a water-swellable rubber device into the superior sagittal sinus, following which imaging, histological, haematological, and behavioural tests were used to investigate pathophysiological changes. Principal component analysis and hierarchical clustering heatmaps were used to evaluate the similarity between the animal models and human patients. RESULTS: The imaging results revealed the possibility of vasogenic oedema in animal models. Haematological analysis indicated an inflammatory and hypercoagulable state. These findings were mostly matched with the retrospective clinical data. Pathological and serological tests further revealed brain parenchymal damage related to CVST in animal models. CONCLUSIONS: We successfully established a stable and reproducible rat model of CVST. The high similarity between clinical patients and animal models was verified via cluster analysis. This model may be useful for the study of CVST pathophysiology and potential therapies.

The Chemical Composition Characteristics and Health Risk Assessment of Cooking Fume Condensates from Residential Kitchens in Different Regions of China.

The aim of this study was to explore the similarities and differences of volatile organic pollutants (VOCs) in cooking fumes (COF) of residential buildings in different regions of China, as well as to evaluate their potential health risks. COF condensates were collected from 10 representative cities in China and analyzed by a GC-MS method. Their effects on α-glucosidase, acetylcholinesterase (AchE), and lactate dehydrogenase (LDH) activities were then detected to evaluate potential health risks. A total of 174 kinds of VOCs, including aldehydes, esters, hydrocarbons, alcohols, and carboxylic acid, were identified. There were 59 identical compounds in the northern and southern regions, and 56 common compounds in spicy and non-spicy regions. Health risk assessment results showed that COF condensate could inhibit the activity of α-glucosidase to varying degrees (61.73-129.25%), suggesting that it had a potential risk of causing hypoglycemia. Daily and 3 and 6 month intakes of COF in minors, adults, and the elderly had both activated and inhibited effects on AchE. The activated effect in the southern and spicy areas was higher than that in northern and non-spicy areas, revealing that different regions and dietary habits had different effects on the risk of neurological diseases caused by changes in AchE activity. For minors, adults, and the elderly, COF had different degrees of activation of LDH at different exposure times and regions. Activation in the northern and non-spicy areas was higher than that in southern and spicy areas, suggesting that the health risks caused by changes in LDH activity levels were significantly increased.

ERCC6L promotes cell growth and metastasis in gastric cancer through activating NF-κB signaling.

ERCC6L has been reported to act as a potential oncogenic protein in various cancers. However, the role of ERCC6L in the progression of gastric cancer (GC) remains to be elucidated. Herein, we aimed to assess the clinical significance, the role, and the underlying mechanism of ERCC6L in GC progression. In this study, the mRNA and protein expression levels of ERCC6L were measured in GC specimens by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry, and its clinical significance was assessed. The effect of ERCC6L overexpression or knockdown on GC cell growth, migration, and invasion was explored by functional experiments. Notably, the possible mechanisms underlying the action of ERCC6L were also investigated. We found that ERCC6L was upregulated in GC tissues, and its expression was associated with tumor size, clinical stage, and poor prognosis in GC patients. Besides, ERCC6L facilitated GC cell proliferation and metastasis in vitro and in vivo. Mechanically, ERCC6L modulated GC cell behavior via activation of NF-κB signaling. Our results indicated that ERCC6L played a critical role in GC progression and metastasis. In addition, ERCC6L promoted GC cell growth and metastasis via activation of NF-κB signaling, thus possibly providing a target for GC.

Upregulated long noncoding RNAs LINC02163 and FEZF1-AS1 exert oncogenic roles in colorectal cancer.

A growing number of evidence has revealed that aberrantly expressed long noncoding RNAs (lncRNAs) are involved in the development of a variety of malignancies, including colorectal cancer (CRC). However, the clinical relevance of most lncRNAs and their potential biological functions in CRC remains poorly understood. The aim of this study was to identify the key lncRNAs related to patient prognosis as well as their biological function and underlying mechanism in CRC. Therefore, five independent datasets containing CRC and normal tissue RNA sequencing, microarray data and the corresponding clinical data from The Cancer Genome Atlas and Gene Expression Omnibus were screened. Hundreds of significantly differentially expressed lncRNAs in CRC were determined, and Kaplan-Meier analyses revealed that some of these lncRNAs were related to the overall survival and progression-free survival of patients with CRC, such as RP11-108K3.2, FOXD3-AS1, H19 and AP001469.9. Among these dysregulated lncRNAs, LINC02163 and FEZF1-AS1 were significantly upregulated in CRC tissues, suggesting that they may have oncogenic roles in CRC. Furthermore, loss of function assays revealed that downregulation of LINC02163 and FEZF1-AS1 impaired CRC cell proliferation. In addition, RNA Immunoprecipitation and Chromatin Immunoprecipitation assays determined that FEZF1-AS1 regulates CRC cell growth via interacting with LSD1 and repressing KLF2 expression. Collectively, hundreds of dysregulated lncRNAs and their associated biological roles identified in this study may provide potentially useful biomarkers and therapeutic targets for CRC.

Galectin-1 promotes vasculogenic mimicry in gastric adenocarcinoma via the Hedgehog/GLI signaling pathway.

BACKGROUND: Galectin-1 (GAL-1), which is encoded by LGALS1, promotes vasculogenic mimicry (VM) in gastric cancer (GC) tissue. However, the underlying mechanism remains unclear. METHODS: Immunohistochemical (IHC) and CD34-periodic acid-Schiff (PAS) double staining were used to investigate Glioma-associated oncogene-1(GLI1) expression and VM in paraffin-embedded sections from 127 patients with GC of all tumor stages. LGALS1 or GLI1 were stably transduced into MGC-803 cells and AGS cells, and western blotting, IHC, CD34-PAS double staining and three-dimensional culture in vitro, and tumorigenicity in vivo were used to explore the mechanisms of GAL-1/ GLI1 promotion of VM formation in GC tissues. RESULTS: A significant association between GAL-1 and GLI1 expression was identified by IHC staining, as well as a significant association between GLI1 expression and VM formation. Furthermore, overexpression of LGALS1 enhanced expression of GLI1 in MGC-803 and AGS cells. GLI1 promoted VM formation both in vitro and in vivo. The effects of GLI1 on VM formation were independent of LGALS1. Importantly, the expression of VM-related molecules, such as MMP2, MMP14 and laminin5γ2, was also affected upon GLI1 overexpression or silencing in GC cell lines. CONCLUSION: GAL-1 promotes VM in GC through the Hh/GLI pathway, which has potential as a novel therapeutic target for treatment of VM in GC.