Quercetin Mediated TET1 Expression Through MicroRNA-17 Induced Cell Apoptosis in Melanoma Cells.

A previous report suggested that the expression of ten-eleven translocation (TET) proteins is abnormal in certain cancers. Quercetin has been demonstrated as anti-cancer role in cancer development. In order to explore the inhibitory effect and mechanism of quercetin on uveal melanoma cells, the expression of TET proteins was analyzed in the present study. Our results suggest that the expression of TET1 was increased following treatment with quercetin in OCM-1, SK-MEL-1, and B16 cells. In addition, quercetin treatment induced apoptosis and inhibited migration and invasion. To further investigate the association of the expression of TET1 with cell growth, apoptosis, migration, and invasion, cell lines in which TET1 was knocked-down or overexpressed were constructed. The results showed that the increased expression of TET1-induced apoptosis, increased 5-hydroxymethylcytosine (5 hmC). and inhibited invasion. Our bioinformatics studies indicated that TET1 is a target gene of microRNA-17 (miR-17) Our results showed that inhibition of the expression of miR-17 resulted in increased TET1 expression in OCM-1 cells. Furthermore, our results indicated that quercetin treatment increased TET1 expression and inhibited melanoma growth in nude mice. Taken together, our results suggest that quercetin can regulate cell proliferation and apoptosis through TET1 via miR-17 in melanoma cells.

Field Network-A New Method to Detect Directional Object.

As the development of object detection technology in computer vision, identifying objects is always an active yet challenging task, and even more efficient and accurate requirements are being imposed on state-of-the-art algorithms. However, many algorithms perform object box regression based on RPN(Region Proposal Network) and anchors, which cannot accurately describe the shape information of the object. In this paper, we propose a new object detection method called Field Network (FN) and Region Fitting Algorithm (RFA). It can solve these problems by Center Field. Center field reflects the probability of the pixel approaching the object center. Different from the previous methods, we abandoned anchors and ROI technologies, and propose the concept of Field. Field is the intensity of the object area, reflecting the probability of the object in the area. Based on the distribution of the probability density of the object center in the visual field perception area, we add the Object Field in the output part. And we abstract it into an Elliptic Field with normal distribution and use RFA to fit objects. Additionally, we add two fields to predict the x,y components of the object direction which contain the neural units in the field array. We extract the objects through these Fields. Moreover, our model is relatively simple and have smaller size, which is only 73 M. Our method improves performance considerably over baseline systems on DOTA, MS COCO and PASCAL VOC datasets, with overall performance competitive with recent state-of-the-art systems.

3D Pose Estimation for Object Detection in Remote Sensing Images.

3D pose estimation is always an active but challenging task for object detection in remote sensing images. In this paper, we present a new algorithm for predicting an object's 3D pose in remote sensing images, called Anchor Points Prediction (APP). Compared to previous methods, such as RoI Transform, our object results of the final output can obtain direction information. We predict the object's multiple feature points based on the neural network to obtain the homograph transformation relationship between object coordinates and image coordinates. The resulting 3D pose can accurately describe the three-dimensional position and attitude of the object. At the same time, we redefine the method I o U A P P for calculating the direction and posture of the object. We tested our algorithm on the HRSC2016 dataset and the DOTA dataset with accuracy rates of 0.863 and 0.701, respectively. The experimental results show that the accuracy of the APP algorithm is significantly improved. At the same time, the algorithm can achieve one-stage prediction, which makes the calculation process easier and more efficient.

miR-375-3p/YWHAZ/ß-catenin axis regulates migration, invasion, EMT in gastric cancer cells.

YWHAZ (14-3-3ζ) plays crucial roles in regulating proliferation, apoptosis, migration, and invasion of gastric cancer (GC) cells. However, its extensive roles and potential mechanisms in GC cells remain unknown, and need to be researched deeply. In this study, we focus on the role of miR-375/YWHAZ axis in migration, invasion and epithelial-to-mesenchymal transition (EMT) of GC cells. YWHAZ level was assessed by western blot and qPCR assays in GC cells. Scratch and transwell assays were used to determine the migration and invasion of GC cells. The protein levels of correlative molecules were detected by western blot. The regulation of miR-375 on the expression of its target gene YWHAZ was verified by dual-luciferase report system. According to the results, knockdown of YWHAZ inhibited the migration, invasion and EMT of GC cells. Moreover, silencing of YWHAZ restrained the activation of wnt/ß-catenin signalling pathway. YWHAZ was confirmed to be a target gene of miR-375, and its expression was regulated by miR-375 in GC cells. Transfection of miR-375 inhibitor promoted the migration, invasion, EMT and activation of wnt/ß-catenin pathway in GC cells, which was suppressed by inhibition of YWHAZ. Taken together, this study suggests that miR-375/YWHAZ axis may be served as a novel therapeutic target for GC patients.

MicroRNA-370 inhibits the proliferation, invasion and EMT of gastric cancer cells by directly targeting PAQR4.

It has been reported that PAQR4 (Progestin and AdipoQ Receptor 4) expression is closely associated with progression of many cancers and microRNA (miRNA) processing. However, the effects and its precise mechanisms of PAQR4 in gastric cancer (GC) have not been well clarified. Our study aimed to explore the interaction between PAQR4 and miR-370 in GC. In our study, we found that the miR-370 level was significantly down-regulated in GC tissues and cell lines, and the expression of PAQR4 was dramatically increased. Interestingly, the low miR-370 level was closely associated with up-regulated PAQR4 expression in GC tissues. Moreover, introduction of miR-370 dramatically suppressed proliferation, invasion and EMT of GC cells. Whereas, miR-370 knockdown increased the proliferation, invasion and EMT in GC cells. We demonstrated that miR-370 could directly target PAQR4 by using both bioinformatics analysis and luciferase reporter assay. In addition, PAQR4 silencing had the similar effects with miR-370 overexpression on GC cells. Overexpression of PAQR4 in GC cells partially reversed the inhibitory effects of miR-370 mimic. miR-370 inhibited cell proliferation, invasion and EMT of GC cells by directly down-regulating PAQR4 expression, and miR-370 targeting PAQR4 was responsible for inhibition of the proliferation, invasion and EMT of GC cells.

TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis.

Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. Methotrexate (MTX) is one of the earliest cytotoxic drugs and serves as an anti-metabolite and anti-folate chemotherapy for various types of cancer. However, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the efficacy of MTX therapies in clinics. Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years. More and more evidences have shown that lncRNAs play regulatory roles in various biological activities and disease progression including drug resistance in cancer cells. Here, we observed lncRNA TUG1 was associated to the MTX resistant in colorectal cancer cells. Firstly, quantitative analysis indicated that TUG1 was significantly increased in tumors which were resistant to MTX treatment. TUG1 knockdown re-sensitized the MTX resistance in colorectal cancer cells, which were MTX-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis.

Luteolin attenuates Staphylococcus aureus-induced endometritis through inhibiting ferroptosis and inflammation via activating the Nrf2/GPX4 signaling pathway.

Endometritis, a local inflammatory disease, has been known as the most common cause of infertility in mares. In this study, we investigated the protective effects of luteolin on endometritis induced by Staphylococcus aureus (S. aureus) and further clarified the possible molecular mechanisms. An S. aureus-induced endometritis model was established by the infusion of S. aureus into the uterus. Luteolin was intraperitoneally administered to mice 1 h before S. aureus treatment. The results showed that the mice of the S. aureus group showed severe histological changes of uterine tissues, increased myeloperoxidase (MPO) activity, and elevated TNF-α, IL-1ß, and IL-6 levels. These changes induced by S. aureus were dose-dependently inhibited by luteolin. Furthermore, luteolin inhibited MDA and Fe2+ production and increased the production of GSH decreased by S. aureus. Luteolin prevented S. aureus-induced endometrial barrier disruption through up-regulating ZO-1 and occludin expression. Luteolin dramatically inhibited S. aureus-induced NF-κB activation. The expression of Nrf2 and HO-1 was increased by luteolin. In addition, the inhibitory effects of luteolin on S. aureus-induced endometritis were reversed in Nrf2 knockdown mice. In conclusion, these data indicated that luteolin protected mice against S. aureus-induced endometritis through inhibiting inflammation and ferroptosis via regulating the Nrf2 signaling pathway.IMPORTANCEEndometritis is an inflammatory disease of the endometrium, which is a common gynecological disease. Up to now, there is no evidence for the protective effects of luteolin on endometritis. The purpose of this study was to investigate whether luteolin has protective effects against S. aureus-induced endometritis and attempts to clarify the mechanism.

Simultaneous quantitation of 15 bioactive components in Yupingfeng granules by LC-MS/MS.

Yupingfeng granules (YPFG) is commonly used in the treatment of immunological diseases, inflammations, and pulmonary diseases. Several studies have found that chromones, flavones, and saponins were the major bioactive compounds of YPFG. However, few studies have reported accurate quantification methods of these compounds. This study aimed to establish a simple and rapid method by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine 15 bioactive compounds in YPFG. The experimental parameters including extraction methods, extraction solvents, extraction time, solid-liquid ratio, and LC-MS/MS condition were optimized. The linearity, precision, repeatability, stability, and recovery of the established method were evaluated. The contents of 15 bioactive compounds in seven batches of YPFG samples were analyzed by the established method and the results were compared with the values determined by HPLC. The optimal extraction condition was to extract 0.1 g of YPFG by ultrasound with 50 mL 50% ethanol for 30 min. A Waters ACQUITY UPLCBEH C18 column using the 0.1% formic acid water solution and acetonitrile as mobile phase with a gradient elution was applied to the chromatographic separation. The linearity, precision, repeatability, stability, and recovery of the method were within acceptable ranges. Compared with HPLC analysis methods in Chinese Pharmacopoeia and literature, the established method was faster, simpler, more accurate, and more reliable. The method of simultaneous determination of 15 components in YPFG by LC-MS might provide a basis for the study of the bioactive compounds and the improvement of the quality standard of YPFG.

Comprehensive Quality Evaluation of Danggui-Jianzhong Decoction by Fingerprint Analysis, Multi-Component Quantitation and UPLC-Q-TOF-MS.

Danggui-Jianzhong decoction (DGJZ) is a famous classical traditional Chinese medicine formula, which ingredients are complex and the quality is difficult to control. Our study aimed to identify the overall chemical profile of DGJZ qualitatively by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and UPLC. A total of 77 components, including terpenoids, flavonoids, phenolic acids, gingerols and other components, were firstly detected and characterized by UPLC-Q-TOF-MS and 18 peaks marked after analyzing the UPLC fingerprint. Finally, paeoniflorin, liquiritin, ferulic acid, cinnamic acid, glycyrrhizic acid and 6-gingerol were quantified, which was validated in terms of linearity, precision, accuracy, repeatability and recovery. Taken together, the chemical constitutes of DGJZ were systematically identified and a reliable quantitative method coupled with fingerprint analysis was successfully employed for evaluating the holistic quality, which will provide a robust foundation for the quality control of DGJZ.

Changes in Tumor Immune Microenvironment after Radiotherapy Resistance in Colorectal Cancer: A Narrative Review.

BACKGROUND: Colorectal cancer (CRC) is a common digestive tract malignancy with high incidence and mortality rates. Radiotherapy is the most common anti-tumor therapeutic regime and is frequently used for treating CRC, especially rectal cancer. However, radiotherapy can lead to tumor resistance to treatment. While previous research on radiotherapy resistance in CRC has mostly focused on the tumor itself, recent advances, especially the emergence of immunotherapy, have led to a greater emphasis on the immune microenvironment of the tumor. SUMMARY: This review has summarized the recent literature on the role of the tumor immune microenvironment in CRC resistance to radiotherapy and provided new ideas for future anti-tumor treatment strategies. KEY MESSAGES: The proportion of immunosuppressive cells is greater than the numbers of cells associated with immune activation, leading to an overall state of immunosuppression; both the tumor and immunosuppressive cells secrete increased amounts of immunosuppressive regulatory factors, reduce the recognition and presentation of tumor antigens, inhibit immune cell's anti-tumor effect, and offset the non-targeted anti-tumor effect of radiotherapy.

By characterizing metabolic and immune microenvironment reveal potential prognostic markers in the development of colorectal cancer.

Colon adenocarcinoma (COAD) is one of the deadliest cancers in the world and survival rates vary significantly between early and advanced stage patients. Therefore, the identification of the pathogenesis in the development of COAD and prognostic markers is urgently demanded. Herein, we collected RNA-seq and somatic mutation data of COAD for statistical analysis. Clinical stage-specific differentially expressed genes (DEGs) and tumor development-dependent DEGs were identified. By characterizing the metabolic and immune features of COAD between stages, we found that the energy supply and inflammatory response of advanced tumors were suppressed. Next, the ETS1, AR, GATA1, GATA2, SREBF1, FOXP3, STAT4, and NFKB1 were identified to drive the metabolic and immune-related pathways in the development of COAD. The three potential prognostic markers (HOXC8, IRF7, and CXCL13) were identified based on Cox regression analysis. Additionally, immune infiltration analysis revealed that the resting CD4+ T cell was significantly related to the overall survival (OS) of COAD patients. Collectively, the specific metabolic and immune characteristics of advanced patients and the identified prognostic biomarkers will contribute to the development of precision medicine.

Surgical Reduction and Direct Repair Using Pedicle Screw-Rod-Hook Fixation in Adult Patients with Low-Grade Isthmic Spondylolisthesis.

Background: Although direct pars repair using a pedicle screw-rod-hook system has achieved satisfactory results in patients with spondylolysis, its application in adults with low-grade isthmic spondylolisthesis is rarely reported. Objective: To assess the surgical effect of reduction and direct repair surgery with a pedicle screw-rod-hook system combined with autogenous bone grafts in adult patients with low-grade isthmic spondylolisthesis. Methods: Sixty-four adult patients with low-grade isthmic spondylolisthesis underwent reduction and direct repair using a pedicle screw-rod-hook system in our department from September 2009 to April 2018. The clinical efficacy was evaluated by clinical and radiological assessments. Results: The average follow-up was 52.15 ± 9.96 months. The visual analog scale (VAS) scores (VAS-lumbar and VAS-leg) and Oswestry Disability Index (ODI) at the final follow-up (FFU) were significantly lower than the preoperative levels (P < 0.05). The modified Prolo score was "excellent" for 60 patients (93.75%) and "good" for 4 patients (6.25%). The slip distance and slipping percentage showed significant decreases postoperatively and FFU compared to preoperatively (P < 0.05). There were no significant differences in the disc height, slip angle, and range of motion of the surgical intervertebral space or upper intervertebral space between preoperation and FFU (P < 0.05). Successful bony fusion had a 96.86% success rate. Conclusion: Reduction of slip and direct repair using pedicle screw-rod-hook fixation combined with autogenous iliac bone grafting in adult patients with low-grade isthmic spondylolisthesis is a safe and effective technique.

The role of RNA modification in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly mortal type of primary liver cancer. Abnormal epigenetic modifications are present in HCC, and RNA modification is dynamic and reversible and is a key post-transcriptional regulator. With the in-depth study of post-transcriptional modifications, RNA modifications are aberrantly expressed in human cancers. Moreover, the regulators of RNA modifications can be used as potential targets for cancer therapy. In RNA modifications, N6-methyladenosine (m6A), N7-methylguanosine (m7G), and 5-methylcytosine (m5C) and their regulators have important regulatory roles in HCC progression and represent potential novel biomarkers for the confirmation of diagnosis and treatment of HCC. This review focuses on RNA modifications in HCC and the roles and mechanisms of m6A, m7G, m5C, N1-methyladenosine (m1A), N3-methylcytosine (m3C), and pseudouridine (ψ) on its development and maintenance. The potential therapeutic strategies of RNA modifications are elaborated for HCC.

Ginkgo biloba Extract Inhibited Cell Proliferation and Invasion by Stimulating TET2 Expression Through miR-29a in Colorectal Carcinoma Cells.

Ginkgo biloba extract (GBE) has antitumor and antioxidant properties, which play a role in regulating gene and protein expression. The ten-eleven translocation (TET) proteins have the ability to regulate epigenetic modifications. However, the abnormal expression of TET2 protein has also been demonstrated in cancer development. In the present study, we analyzed the effects of GBE administration on TET2 expression in human colorectal cancer (CRC). The Cancer Genome Atlas database suggested that the expression of TET2 was lost in CRC. To investigate the expression profiles of TET2, GBE was used to treat CRC cells. The results showed that GBE could increase the expression of TET2 and 5-hydroxymethylcytosine (5hmC). In addition, GBE inhibited cell growth and invasion in SW480 cells. Moreover, to confirm whether TET2 expression affected cell proliferation, apoptosis, migration, and invasion, TET2 was knocked down and a TET2-overexpressing vector was constructed in human CRC cells. The results showed that overexpression of TET2 induced cell proliferation and invasion. Bioinformatic analyses showed that TET2 is a target gene of microRNA-29a (miR-29a). Moreover, reduced expression of miR-29a and increased TET2 expression in CRC cells. GBE was also used to treat a tumor model in nude mice. Compared to the control group, tumor growth was inhibited, and there was increased expression of TET2 in the GBE-treatment group in vivo. In conclusion, these results indicated that GBE inhibited cell proliferation and invasion through TET2 protein expression regulated by miR-29a in the development of CRC.

Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers.

Bile duct, pancreatic, and gastric cancers are deadly digestive system tumors with high malignancy and poor patient prognosis. The efficiencies of conventional surgical treatment, radiation therapy, and chemotherapy are limited. In contrast, chimeric antigen receptor (CAR) T-cell therapy represents a landmark therapeutic approach to antitumor immunity with great efficacy in treating several hematological malignancies. CAR T-cell therapy involves genetically engineering the expression of specific antibodies based on the patient's T-cell surface and amplifying these antibodies to identify and target tumor-associated antigens. CAR T-cell therapy can effectively inhibit disease progression and improve the survival of patients with bile duct, pancreatic, and gastric cancers. The effectiveness of CAR T cells in tumor therapy can be validated using xenograft models, providing a scientific testing platform. In this study, we have reviewed the progress in CAR T-cell production and its development, focusing on the current status and optimization strategies for engineered CAR T cells in the bile duct, pancreatic, and gastric cancers.

The application of collagen in the repair of peripheral nerve defect.

Collagen is a natural polymer expressed in the extracellular matrix of the peripheral nervous system. It has become increasingly crucial in peripheral nerve reconstruction as it was involved in regulating Schwann cell behaviors, maintaining peripheral nerve functions during peripheral nerve development, and being strongly upregulated after nerve injury to promote peripheral nerve regeneration. Moreover, its biological properties, such as low immunogenicity, excellent biocompatibility, and biodegradability make it a suitable biomaterial for peripheral nerve repair. Collagen provides a suitable microenvironment to support Schwann cells' growth, proliferation, and migration, thereby improving the regeneration and functional recovery of peripheral nerves. This review aims to summarize the characteristics of collagen as a biomaterial, analyze its role in peripheral nerve regeneration, and provide a detailed overview of the recent advances concerning the optimization of collagen nerve conduits in terms of physical properties and structure, as well as the application of the combination with the bioactive component in peripheral nerve regeneration.

Interferon and interferon-stimulated genes in HBV treatment.

Human hepatitis B virus (HBV) is a small enveloped DNA virus with a complex life cycle. It is the causative agent of acute and chronic hepatitis. HBV can resist immune system responses and often causes persistent chronic infections. HBV is the leading cause of liver cancer and cirrhosis. Interferons (IFNs) are cytokines with antiviral, immunomodulatory, and antitumor properties. IFNs are glycoproteins with a strong antiviral activity that plays an important role in adaptive and innate immune responses. They are classified into three categories (type I, II, and III) based on the structure of their cell-surface receptors. As an effective drug for controlling chronic viral infections, Type I IFNs are approved to be clinically used for the treatment of HBV infection. The therapeutic effect of interferon will be enhanced when combined with other drugs. IFNs play a biological function by inducing the expression of hundreds of IFN-stimulated genes (ISGs) in the host cells, which are responsible for the inhibiting of HBV replication, transcription, and other important processes. Animal models of HBV, such as chimpanzees, are also important tools for studying IFN treatment and ISG regulation. In the present review, we summarized the recent progress in IFN-HBV treatment and focused on its mechanism through the interaction between HBV and ISGs.

Non-coding RNAs in diabetes mellitus and diabetic cardiovascular disease.

More than 10% of the world's population already suffers from varying degrees of diabetes mellitus (DM), but there is still no cure for the disease. Cardiovascular disease (CVD) is one of the most common and dangerous of the many health complications that can be brought on by DM, and has become the leading cause of death in people with diabetes. While research on DM and associated CVD is advancing, the specific mechanisms of their development are still unclear. Given the threat of DM and CVD to humans, the search for new predictive markers and therapeutic ideas is imminent. Non-coding RNAs (ncRNAs) have been a popular subject of research in recent years. Although they do not encode proteins, they play an important role in living organisms, and they can cause disease when their expression is abnormal. Numerous studies have observed aberrant ncRNAs in patients with DM complications, suggesting that they may play an important role in the development of DM and CVD and could potentially act as biomarkers for diagnosis. There is additional evidence that treatment with existing drugs for DM, such as metformin, alters ncRNA expression levels, suggesting that regulation of ncRNA expression may be a key mechanism in future DM treatment. In this review, we assess the role of ncRNAs in the development of DM and CVD, as well as the evidence for ncRNAs as potential therapeutic targets, and make use of bioinformatics to analyze differential ncRNAs with potential functions in DM.

Corrigendum: Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers.

[This corrects the article DOI: 10.3389/fimmu.2022.1025608.].