Colorectal cancer (CRC) ranks as the third most prevalent contributor to global disease burden and represents the second highest mortality rate among all malignancies worldwide. Long non-coding RNAs (lncRNAs) are a new class of regulatory RNAs, which play a crucial role in the occurrence and development of colorectal cancer. Therefore, it is potentially important to use bioinformatics and machine learning methods to study novel biomarkers for CRC. The RNA-seq data of colorectal cancer and normal colorectal tissue were downloaded from the GEO database. Random forest (RF) and LASSO (Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms were constructed to screen lncRNAs closely related to CRC, and their screening efficiency was verified. Predict the regulatory genes of lncRNA and construct the ceRNA regulatory network of lncRNA-miRNA-mRNA. Quantitative real-time PCR (qRT-PCR) was used to verify its expression in colorectal cancer tissues and adjacent tissues, as well as its relationship with clinical features of CRC patients. A total of 3028 CRC-related lncRNAs were initially screened from the GEO database, and 55 differentially expressed lncRNAs (DE lncRNAs) were finally selected through difference analysis. The key lncRNAs were further screened using RF and LASSO. The same gene in the screening results of the above two methods was selected as the key lncRNA of CRC. Finally, five key lncRNAs (NCAL1, CRNDE, HMGA1P4, EPIST and MT1JP) were selected, among them, the expressions of NCAL1, CRNDE and HMGA1P4 were upregulated compared with normal CRC tissues, while the expressions of EPIST and MT1JP were downregulated compared with normal colorectal tissues. The expression of 5 key CRC lncRNAs was verified, and each AUC is greater than 0.7, indicating a good screening effect. Since CRNDE has been studied by members of this research group before, it will not be further studied. It was predicted that 4 lncRNAs would interact with 16 miRNAs and 57 mRNAs. Four key lncRNAs, namely NCAL1, HMGA1P4, EPIST and MT1JP, were experimentally verified. qRT-PCR results showed that the expression of four key lncRNAs in CRC tissues and adjacent tissues had statistical significance (p < 0.001). In summary, we obtained 5 lncRNAs that may be closely related to colorectal cancer, including NCAL1, CRNDE, HMGA1P4, EPIST and MT1JP. This study found that NCAL1, HMGA1P4, EPIST and MT1JP may be candidate biomarkers for colorectal cancer.

Amino acids are considered an important class of clinical biomarkers, but their low physiological concentrations and conformational similarity demand biosensing technologies with exceptional sensitivity and specificity. Based on electromagnetic localization and molecular recognition, Terahertz (THz) metamaterial has been reported for trace detection. However, conventional approaches rely on surface modifications and exhibit limited detection limits (similar to nmol/mu L), underutilizing the potential of THz spectral fingerprints. A THz metamaterial biosensor integrating the toroidal dipole quasi-bound state in the continuum (TD-QBIC) principle with resonance frequency matching between the metamaterial and amino acid fingerprint frequencies is presented here. This dual mechanism dramatically enhances THz-analyte interactions, thereby optimizing both sensitivity and specificity in amino acid detection. In this work, a metamaterial was designed through electromagnetic simulations to feature a high quality (Q) factor toroidal dipole bound state in the continuum (TD-BIC) mode at 0.35 THz for sensitivity enhancement, along with a dipole resonance at 0.86 THz aligned with arginine's intrinsic vibrational fingerprint for specificity. The device was fabricated using photolithography and experimentally characterized via terahertz time-domain spectroscopy (THz-TDS). Results demonstrate a record-low limit of detection (LoD) of 10 pmol/mu L for arginine, surpassing existing THz biosensors by three orders of magnitude. Specificity is confirmed by distinct transmission responses at 0.86 THz (Delta I% = 13.12 % for arginine vs. <= 5.40 % for interferents). Clinical validation with human sweat demonstrates strong correlation with ELISA (R-2 >= 0.99), establishing its diagnostic reliability. This work synergizes spectral fingerprinting with high-Q resonance engineering, advancing label-free biosensing for precision diagnostics.

The detection of extremely rare circulating tumor cells (CTCs) in peripheral blood and simultaneously identifying their viabilities are significant for cancer diagnosis and prognosis as well as monitoring the efficacy of personalized treatment. A lens-free imaging system features high-resolution images taken over a large field of view (FOV), which has great potential for CTC detection and viability determination. But current still lens-free systems restrict the application for CTC detection in real samples due to the inherent limitations of lens-free technology: (1) the location of cells in the FOV will affect the imaging; (2) the extremely rare CTCs probably did not exist in one observation. In this paper, we realized the detection of CTCs in whole blood and the simultaneous determination of their viabilities by lens-free imaging cytometry. Our in-flow system plus a large FOV range of lens-free imaging highly increased the detection rate of rare CTCs with a high throughput of 150,000 cells per minute and improved the recognition efficiency for blood cells, living/dead CTCs by using a cell tracing-assisted deep learning algorithm. With this method, the average precision of blood cells, living/dead lung cancer cells A549, and living/dead colon cancer cells SW620 reached 98.80%, 97.88%, 97.93%, 97.72%, and 98.60%, respectively. Our system got a highly consistent result with the manual counting method using fluorescent staining (Pearson's r 99.93% for SW620) and can easily detect as few as 10 dead or living CTCs from 100,000 white blood cells (WBCs). Finally, real clinical samples were detected in our system. Both dead and living CTCs were found in all six advanced-stage cancer patients, and the number of living CTCs per million WBCs ranged from 13 to 39, more than that of the dead CTCs (5 to 25), while none of the CTCs were detected in six healthy control subjects. Moreover, we also found that CTCs died very quickly after leaving the human body, indicating that CTCs should be studied as soon as possible after sampling. Although this method is implemented for CTCs, it can also be used for the detection of other rare cells.

The CRISPR/Cas12a system is increasingly used in biosensor development. However, high background signal and low sensitivity for the non-nucleic acid targets detection is challenging. Here, a padlock activator which could inhibit the trans-cleavage activity of CRISPR/Cas12a system in the intact form by steric hindrance effect (PAIT effect) was designed for non-nucleic acid targets detection. The PAIT effect disappeared when padlock activator was separated into two split activators. To verify the feasibility of padlock activator, a Ca2+ sensor was developed based on PAIT effect with the assistance of DNAzyme, activity of which was Ca2+ dependent. In the presence of Ca2+, DNAzyme was activated to cleave its substrate, a padlock activator modified with adenine ribonucleotide, into split padlock activators which would trigger the trans-cleavage activity of Cas12a to generate fluorescence. There was a mathematical relationship between the fluorescence intensity and the logarithm of Ca2+ concentration ranging from 10 pM to 1 nM, with a limit of detection of 3.98 pM. The little interference of Mg2+, Mn2+, Cd2+, Cu2+, Na+, Al3+, K+, Fe2+, and Fe3+ indicated high selectivity. Recovery ranged from 93.32% to 103.28% with RSDs from 1.87% to 12.74% showed a good accuracy and reliability. Furthermore, the proposed sensor could be applied to detect Ca2+ in mineral water, milk powder and urine. The results were consistent with that of flame atomic absorption spectroscopy. Thus, PAIT effect is valuable for expanding the application boundary of CRISPR/Cas12a system.

The C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-albumin ratio (NAR) serve as established markers for inflammatory diseases. However, limited studies have investigated their potential in predicting response and prognosis following infliximab (IFX) treatment. The objective of this paper was to evaluate feasibility of CAR and NAR as biomarkers to assess response to IFX induction therapy. Additionally, we attempted to determine the capacity to predict clinical remission in ulcerative colitis (UC) after 54 weeks of IFX treatment. We enrolled a total of 157 UC patients diagnosed via endoscopic mucosal biopsy at our hospital between October 2018 and June 2023. Additionally, 199 patients presenting with gastrointestinal symptoms, who underwent physical examinations, constituted the control group. Comprehensive clinical data, laboratory indicators, and endoscopic findings were systematically collected. CAR and NAR values were computed before treatment, post-induction, and subsequently at 8-week intervals. Comparisons between two groups were analyzed using the Wilcoxon rank-sum test or the independent samples t-test, and comparisons between multiple groups were analyzed using the one-way ANOVA (analysis of variance) or the Kruskal-Wallis rank sum test. We found CAR and NAR emerged as sensitive biomarkers for assessing disease activity. Notably, our findings indicated their dual predictive capability: foreseeing response post-IFX induction therapy and prognosticating the likelihood of UC patients achieving clinical remission following 54 weeks on IFX therapy.

Exosome analysis plays pivotal roles in various physiological and pathological processes. Plasmonic scattering microscopy (PSM) has proven to be an excellent label-free imaging platform for exosome detection. However, accurately detecting images scattered from exosomes remains a challenging task due to noise interference. Herein, we proposed an image processing strategy based on a new blind super-resolution deep learning neural network, named ESRGAN-SE, to improve the resolution of exosome PSI images. This model can obtain super-resolution reconstructed images without increasing experimental complexity. The trained model can directly generate high-resolution plasma scattering images from low-resolution images collected in experiments. The results of experiments involving the detection of light scattered by exosomes showed that the proposed super-resolution detection method has strong generalizability and robustness. Moreover, ESRGAN-SE achieved excellent results of 35.52036, 0.09081, and 8.13176 in terms of three reference-free image quality assessment metrics, respectively. These results show that the proposed network can effectively reduce image information loss, enhance mutual information between pixels, and decrease feature differentiation. And, the single-image SNR evaluation score of 3.93078 also showed that the distinction between the target and the background was significant. The suggested model lays the foundation for a potentially successful approach to imaging analysis. This approach has the potential to greatly improve the accuracy and efficiency of exosome analysis, leading to more accurate cancer diagnosis and potentially improving patient outcomes.

S100 family members (S100s) are small molecular EF hand calcium binding proteins and widely expressed in many tissues and organs. S100s are shown to be biomarkers of disease progression and prognosis in various types of cancers. Nevertheless, the expression patterns, function, and prognostic values of S100s and its association with tumor-infiltrating immune cells in pancreatic adenocarcinoma (PAAD) patients have not been systematically clarified. We explored the expression and roles of the entire 20 S100s in PAAD patients by using the following public databases: Oncomine, gene expression profiling interactive analysis, cBioPortal, Metascape, search tool for recurring instances of neighboring genes, Tumor IMmune Estimation Resource, and GeneMANIA. The S100A2/A3/A4/A6/A8/A9/A10/A11/A13/A14/A16/B/P mRNA expressions were significantly upregulated in PAAD patients. The mRNA expression of S100A3/A4/A5/A6/A10/A11/A14/A16/Z were significantly negatively related with the tumor stage in PAAD patients. We found that the S100A2/A3/A5/A10/A11/A14/A16 were significantly correlated with poor overall survival, whereas the increased levels of S100A1/B/G/Z were strongly associated with good overall survival. We found significant correlations among S100s and tumor-infiltrating immune cells. Cox proportional risk models revealed that B cells, Dendritic cells and S100A1/A5/A6/A8/A9/A13/A14 were significantly related with outcomes in PAAD patients. These results suggest that S100A2/A3/A10/A11/A14/A16 may serve as new diagnostic and prognostic biomarkers for PAAD patients and provide new clues for immunotherapy in PAAD patients.

N6-methyladenosine (m6A) serves as a major RNA methylation modification and impacts the initiation and progression of various human cancers through diverse mechanisms. It has been reported that m6A RNA methylation is involved in different physiological and pathological processes, including stem cell differentiation and motility, immune response, cellular stress, tissue renewal and viral infection. In this review, the m6A modification and its regulatory functions in a few major cancers is introduced. The detection approaches for the m6A sites identification are discussed. Additionally, the potential of the RNA m6A modification in clinical application is discussed.

A 44-year-old man went to the local hospital with a 3-day history of nausea, vomiting, abdominal pain, and difficulty eating after drinking. Gastrointestinal endoscopy showed a kidney-shaped bezoar obstructing the esophagus at 30 cm from incisors. On esophagography, the esophageal walls were seen to be stretched thin by the large bezoar (▶Fig. 1). Computed tomography scanning showed that the bezoar, which was located in the lower esophagus, was about 30-mm wide, 25mm in the anteroposterior direction, and 53mm in length (▶Fig. 2 a, b). Multiplanar reformation showed that the bezoar was close to the major blood vessels and heart (▶Fig. 2 c). On day 4 of admission, the patient underwent laser lithotripsy. After the bezoar had been partially broken up by the lithotripsy, we attempted removal with a wireguided retrieval basket and snare, but neither were successful (▶Video 1). Laser lithotripsy was performed again. The broken bezoar fragments were then pushed into the stomach and crushed by the wire-guided retrieval basket. Once the bezoar had been removed from the esophagus, multiple ulcers, including two large ones, were seen at 30–36 cm from the incisors (▶Fig. 3 a). Following the lithotripsy procedure, the patient was treated with sodium bicarbonate to facilitate dissolution of the bezoars. At follow-up 1 month later, gastroscopy showed that the bezoars had disappeared and the esophageal ulcers were well healed (▶Fig. 3b). Esophageal bezoars are rare, in contrast to the more common gastric bezoars. Esophageal bezoars are often associated with mechanical obstruction of the esophagus or reflux of gastric bezoars [1, 2]. A bezoar that lodges in the esophagus often causes acute obstruction; its most acute onset can cause chest pain and difficulty in swallowing. If the bezoar is incarcerated in the esophagus for a longer time, the esophageal wall can ulcerate, bleed, and even perforate [3]. Usually, a wire-guided retrieval basket or snare is used as the first approach for foreign body removal in the esophagus [4, 5]; however, alternative methods to manage large foreign bodies should be considered. As in our case, the hard bezoar was E-Videos

PURPOSE:We aimed to study the role of anoikis-related genes (ARGs) in colorectal cancer (CRC) using bioinformatics. METHODS:GSE39582 and GSE39084, which collectively contain 363 CRC samples, were downloaded from the NCBI Gene Expression Omnibus (GEO) database as a test set. TCGA-COADREAD, with 376 CRC samples, was downloaded from the UCSC database as a validation set. Univariate Cox regression analysis was used to screen for ARGs that were significantly associated with prognosis. The top 10 ARGs were used to classify the samples into different subtypes based on unsupervised cluster analysis. The immune environments of the different subtypes were analyzed. ARGs that were significantly associated with CRC prognosis were used to construct a risk model. Univariate and multivariate Cox regression analyses were used to screen independent prognostic factors and construct a nomogram. RESULTS:Four anoikis-related subtypes (ARSs) with differential prognoses and immune microenvironments were identified. KRAS and epithelial-mesenchymal transition pathways were enriched in subtype B, which had the worst prognosis. Three ARGs (DLG1, AKT3, and LPAR1) were used to construct the risk model. Both the test and validation sets showed worse outcomes for patients in the high-risk group than those in the low-risk group. Risk score was found to be an independent prognostic factor for CRC. Moreover, there was a difference in drug sensitivity between the high- and low-risk groups. CONCLUSION:The identified ARGs and risk scores were associated with CRC prognosis and could predict the responses of patients with CRC to immunotherapy strategies.

In the fight against the worldwide pandemic coronavirus disease 2019 (COVID-19), simple, rapid, and sensitive tools for nucleic acid detection are in urgent need. PCR has been a classic method for nucleic acid detection with high sensitivity and specificity. However, this method still has essential limitations due to the dependence on thermal cycling, which requires costly equipment, professional technicians, and long turnover times. Currently, clustered regularly interspaced short palindromic repeats (CRISPR)-based biosensors have been developed as powerful tools for nucleic acid detection. Moreover, the CRISPR method can be performed at physiological temperature, meaning that it is easy to assemble into point-of-care devices. Microfluidic chips hold promises to integrate sample processing and analysis on a chip, reducing the consumption of sample and reagent and increasing the detection throughput. This review provides an overview of recent advances in the development of CRISPR-based biosensing techniques and their perfect combination with microfluidic platforms. New opportunities and challenges for the improvement of specificity and efficiency signal amplification are outlined. Furthermore, their various applications in healthcare, animal husbandry, agriculture, and forestry are discussed.

Gastric cancer is one of the most common cancers with few effective treatments, a new treatment agent is desperately needed. C-2, a Jaspine B derivative, has shown anti-cancer efficacy in gastric cancer cells. The anticancer mechanism, however, remains unknown. As a result, we investigate the anti-cancer effect and the underlying mechanism of C-2 in gastric cancer cells. The results showed that C-2 selectively reduced the proliferation of gastric cancer cells when compared to normal epithelial gastric cells. Western blotting and flow cytometry further demonstrated that Caspase9 is involved in causing cell death. Meanwhile, C-2 triggered autophagy in gastric cancer cells, inhibition of which with LY294002 can enhance the anti-proliferative activity of C-2. Next, we found that C-2 triggered autophagy through activating JNK/ERK, and that inhibitors of these proteins exacerbated C-2 induced cell death. Mechanically, enhanced phosphorylation of JNK/ERK elevated Beclin-1 by disturbing Beclin-1/Bcl-xL or Beclin-1/Bcl-2 complexes, resulting in autophagy and up-regulation of p62. Finally, p62 binds Keap1 competitively to release Nrf2, boosting Nrf2 translocation from the cytoplasm to the nucleus and triggering expression of Nrf2 target genes, so enhancing survival. C-2 inhibited the growth of gastric cancer cells, while JNK/ERK dependent autophagy antagonized C-2 induced cell growth inhibition through p62/Keap1/Nrf2 pathway.

BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. A total of 45 kinesin superfamily proteins (KIFs) have been identified in humans, among which several family members have demonstrated varied functions in tumor pathobiology via different mechanisms, including regulation of cell cycle progression and metastasis. KIFC3 has microtubule motor activity and is involved in cancer cell invasion and migration, as well as survival. However, the role of KIFC3 in ESCC is still unknown. AIM:To evaluate the role of KIFC3 in ESCC and the underlying mechanisms. METHODS:Expression of KIFC3 was evaluated in ESCC tissues and adjacent normal esophageal tissues. The prognostic value of KIFC3 was analyzed using Kaplan-Meier Plotter. Colony formation, EdU assays, cell cycle analysis, Transwell assay, immunofluorescence, and western blotting were performed in ESCC cell lines after transfection with pLVX-Puro-KIFC3-shRNA- and pLVX-Puro-KIFC3-expressing lentiviruses. A xenograft tumor model in nude mice was used to evaluate the role of KIFC3 in tumorigenesis. Inhibitor of β-catenin, XAV-939, was used to clarify the mechanism of KIFC3 in ESCC. To analyze the differences between groups, t test and nonparametric tests were used. P < 0.05 was considered statistically significant. RESULTS:Immunohistochemical staining indicated that KIFC3 was upregulated in ESCC tissues compared with adjacent normal tissues. Kaplan-Meier Plotter revealed that overexpressed KIFC3 was associated with poor prognosis in ESCC patients. Colony formation and EdU assay showed that KIFC3 overexpression promoted cell proliferation, while KIFC3 knockdown inhibited cell proliferation in ESCC cell lines. In addition, cell cycle analysis showed that KIFC3 overexpression promoted cell cycle progression. KIFC3 knockdown suppressed ESCC tumorigenesis in vivo. Transwell assay and western blotting revealed that KIFC3 overexpression promoted cell migration and invasion, as well as epithelial-mesenchymal transition (EMT), while KIFC3 knockdown showed the opposite results. Mechanistically, KIFC3 overexpression promoted β-catenin signaling in KYSE450 cells; however, the role of KIFC3 was abolished by XAV-939, the inhibitor of β-catenin signaling. CONCLUSION:KIFC3 was overexpressed in ESCC and was associated with poor prognosis. Furthermore, KIFC3 promoted proliferation, migration and invasion of ESCC via β-catenin signaling and EMT.

Emerging evidence indicates the early growth response 1 (Egr1) plays an important role in the pathogenesis of chronic pain. However, the regulation of Egr1 expression in the DRG and spinal cord in neuropathic pain remains unclear. In the current study, the neuropathic pain was conducted by lumber 5 spinal nerve ligation (SNL) in rats. The role of miR-124-3p in Egr1 expression was examined. Our results showed that the SNL led to a significant increase in the expression of Egr1 mRNA and protein in the DRG and dorsal horn. This increased expression of Egr1 correlated with a reduction of miR-124-3p in the same region. Prior i.t. injection of Egr1 decoy AYX1 inhibited the expression of Egr1 and attenuated the neuropathic pain-like hypersensitivity following SNL. The dual-luciferase reporter assay revealed the luciferase activity of the Egr1 3 '-UTR plasmid was inhibited by the miR-124-3p agomir. But this inhibition was completely reversed in the mutant 3 '-UTR Egr1 group. In vivo, the SNL-induced behavioral signs of neuropathic pain and the increases in Egr1 mRNA and protein in the DRG and dorsal horn were prevented by prior to i.t. injection of miR-124-3p agomir. While, i.t. injection of miR-124-3p antagomir in naive rats resulted in mechanical allodynia and thermal hyperalgesia and an overexpression of Egr1 in the DRG and dorsal horn. Together, our results suggest that the miR-124-3p-regulated Egr1 expression in the DRG and dorsal horn contributes to the development of neuropathic pain. Targeting miR-124-3p might be a promising therapeutic strategy in the treatment of chronic pain.

The effect of circular RNA MTO1 (circMTO1) signaling on the expression of miR-199a-3p in gastric carcinoma cells, and its effect on proliferation and apoptosis of gastric cancer cells were investigated in this study. RT-qPCR was performed to detect the expression levels of circMTO1 and miR-199a-3p in the cell lines and tissues of gastric cancer. The effect of circMTO1 and miR-199a-3p on the growth and apoptosis of tumor cells was detected by BrdU incorporation and Annexin V/PI staining. Target gene prediction and screening, and luciferase reporter assays were performed to validate downstream interested genes of circMTO1 and miR-199a-3p. The expression levels of miR-199a-3p target gene PAWR (named as PRKC apoptosis WT1 Regulator Protein) was measured by RT-qPCR and Western blotting. Tumor changes in mice were detected by transfecting circMTO1. The expression of circMTO1 was significantly downregulated in the cell lines and tissues of gastric cancer, and low expression levels of circMTO1 were closely associated with poor prognosis. Overexpression of circMTO1 inhibited tumor growth, enhanced apoptosis rate and decreased cell invasion and migration. There was a significant negative relationship between the expression levels of circMTO1 and miR-199a-3p in gastric cancer tissues. Inhibiting miR-199a-3p expression or overexpression of PAWR could decrease the promotive effects of knockdown of circMTO1 on the progression of gastric cancer, and a positive relationship was established between the expression of circMTO1 and PAWR. circMTO1 can regulate the growth of gastric cancer cells by regulating miR-199a-3p/PAWR axis, thus inhibiting the development and progression of gastric cancer. Abbreviation GC: Gastric cancer; circ RNA: Circular RNA; MTO1: mitochondrial translation optimized 1 homolog.

The effect of circular RNA MTO1 (circMTO1) signaling on the expression of miR-199a-3p in gastric carcinoma cells, and its effect on proliferation and apoptosis of gastric cancer cells were investigated in this study. RT-qPCR was performed to detect the expression levels of circMTO1 and miR-199a-3p in the cell lines and tissues of gastric cancer. The effect of circMTO1 and miR-199a-3p on the growth and apoptosis of tumor cells was detected by BrdU incorporation and Annexin V/PI staining. Target gene prediction and screening, and luciferase reporter assays were performed to validate downstream interested genes of circMTO1 and miR-199a-3p. The expression levels of miR-199a-3p target gene PAWR (named as PRKC apoptosis WT1 Regulator Protein) was measured by RT-qPCR and Western blotting. Tumor changes in mice were detected by transfecting circMTO1. The expression of circMTO1 was significantly downregulated in the cell lines and tissues of gastric cancer, and low expression levels of circMTO1 were closely associated with poor prognosis. Overexpression of circMTO1 inhibited tumor growth, enhanced apoptosis rate and decreased cell invasion and migration. There was a significant negative relationship between the expression levels of circMTO1 and miR-199a-3p in gastric cancer tissues. Inhibiting miR-199a-3p expression or overexpression of PAWR could decrease the promotive effects of knockdown of circMTO1 on the progression of gastric cancer, and a positive relationship was established between the expression of circMTO1 and PAWR. circMTO1 can regulate the growth of gastric cancer cells by regulating miR-199a-3p/PAWR axis, thus inhibiting the development and progression of gastric cancer.

LncRNA GAS8-AS1 inhibits thyroid carcinoma, while its role in colorectal cancer (CRC) is unknown. In the present study we found that plasma GAS8-AS1 was upregulated in early stage CRC patients, and downregulation of GAS8-AS1 effectively distinguished CRC patients from healthy controls. LncRNA AFAP1-AS1 was upregulated in CRC patients and was inversely correlated with GAS8-AS1 only in CRC patients but not in healthy controls. GAS8-AS1 overexpression mediated the downregulation of AFAP1-AS1 in colon cancer cells, while AFAP1-AS1 overexpression did not significantly affect GAS8-AS1 expression. Expression level of GAS8-AS1 decreased, while expression level of AFAP1-AS1 increased with the increase of primary tumor diameters. GAS8-AS1 overexpression led to inhibited, while AFAP1-AS1 overexpression led to promoted proliferation of CRC cells, and AFAP1-AS1 overexpression reduced the inhibitory effects of GAS8-AS1 overexpression on cancer cell proliferation. Therefore, GAS8-AS may inhibit CRC cell proliferation by downregulating AFAP1-AS1.

Ulcerative colitis is closely associated with colorectal cancer, the long-standing chronic inflammation being the key etiology of ulcerative colitis. The aim of the present study was to identify the anti-inflammatory and anti-apoptosis activity of taraxasterol in ulcerative colitis. MTT assay was used to obtain the optimal concentrations of lipopolysaccharide (LPS) and taraxasterol for cell treatments in vitro. A mouse model of colitis was established via dextran sodium sulphate (DSS) administration. Levels of IL-6 and TNF-α were detected through ELISA. Flow cytometry and western blotting were used to detect apoptosis and related protein expression levels, respectively. Hematoxylin and eosin staining was performed to detect the pathological damage. The results from the MTT assay identified the optimal concentration of LPS and taraxasterol, and ELISA results demonstrated that taraxasterol treatment decreased the expression levels of IL-6 and TNF-α in vitro and in vivo, in a dose-dependent manner. Taraxasterol treatment inhibited apoptosis, and reduced the protein levels of p53, Bcl-2 associated X (BAX) and caspase-3. Finally, pathological damages were reduced in colonic tissues of mice treated with taraxasterol. Taken together, taraxasterol treatment markedly inhibited inflammation and apoptosis in ulcerative colitis. Therefore, taraxasterol may be a promising agent for decreasing the inflammatory response in ulcerative colitis and other inflammation-related diseases.

MIR210HG is a novel long noncoding RNA (lncRNA) and has been found to be overexpresed in osteosarcoma and glioma. However, the level of MIR210HG and its clinical significance in hepatocellular carcinoma (HCC) are not well known. In results of our research, MIR210HG expression was increased in HCC tissue samples and cells compared with paired adjacent normal liver tissue samples and normal liver cell line respectively, and a good marker to discriminate HCC tissues from non-tumorous tissues. MIR210HG high-expression was correlated advanced clinical stage, big tumor size, present vascular invasion and unfavorable histological differentiation. The survival analysis from our cohort and TCGA cohort consistently suggested that HCC patients with MIR210HG high-expression had poorer prognosis than HCC patients with MIR210HG low-expression. Furthermore, univariate and multivariate Cox regression analyses showed that MIR210HG high-expression was an independent unfavorable prognostic factor for overall survival in HCC patients. The in vitro study showed that silencing of MIR210HG depressed HCC cell proliferation, migration and invasion. In conclusion, MIR210HG functions as an oncogenic lncRNA in HCC, and may be a potential biomarker for predicting clinical progression and prognosis.

The aim of this article is to investigate the effects of intra-abdominal infection on immunological function and high-mobility group box 1 protein (HMGB1)/toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in patients with severe acute pancreatitis (SAP). Clinical data of SAP patients were retrospectively analyzed. SAP patients were divided into intra-abdominal infection group (103 SAP patients) and control group (115 SAP patients without intra-abdominal infection). All patients were evaluated with the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Enzyme-linked immunosorbent assay (ELISA) assays were used to detect the levels of serum endotoxin, d-lactate, diamine oxidase, IgG, IgM, IgA, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and HMGB1. Western blotting was performed to detect the levels of TLR4 and NF-κB in peripheral blood lymphocytes. Compared with control group, the APACHE II score (12.60 ± 3.81 vs 9.55 ± 3.02) and serum endotoxin (0.33 ± 0.15 vs 0.19 ± 0.09 EU/mL), d-lactate (4.33 ± 0.16 vs 4.02 ± 0.12 mg/L), and diamine oxidase (3.88 ± 0.16 vs 3.65 ± 0.13 EU/mL) levels in intra-abdominal infection group were increased significantly (all P < 0.001); serum IgG (7.33 ± 0.82 vs 9.05 ± 0.90 g/L), IgM (1.04 ± 0.49 vs 1.18 ± 0.53 g/L), and IgA (1.65 ± 0.79 vs 1.96 ± 0.88 g/L) levels in intra-abdominal infection group were decreased significantly, while serum IL-1β (118.55 ± 17.04 vs 83.61 ± 12.28 ng/L), IL-6 (12.05 ± 7.69 vs 9.89 ± 6.77 ng/L), TNF-α (25.61 ± 8.76 vs 19.20 ± 8.33 ng/L), and HMGB1 (48.91 ± 20.63 vs 32.74 ± 17.05 μg/L) levels were increased significantly (all P < 0.05); TLR4 and NF-κB in intra-abdominal infection group were increased significantly (both P < 0.001). The intra-abdominal infection can lead to intestinal barrier dysfunction, aggravated inflammatory response, and immune dysfunction in SAP patients, which may be related to the activation of HMGB1/TLR4/NF-κB pathway caused by intra-abdominal infection.