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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

The Biology and Function of Extracellular Vesicles in Cancer Development.

Extracellular vesicles (EVs) exert their biological functions by delivering proteins, metabolites, and nucleic acids to recipient cells. EVs play important roles in cancer development. The anti-tumor effect of EVs is by their cargos carrying proteins, metabolites, and nucleic acids to affect cell-to-cell communication. The characteristics of cell-to-cell communication can potentially be applied for the therapy of cancers, such as gastric cancer. In addition, EVs can be used as an effective cargos to deliver ncRNAs, peptides, and drugs, to target tumor tissues. In addition, EVs have the ability to regulate cell apoptosis, autophagy, proliferation, and migration of cancer cells. The ncRNA and peptides that were engaged with EVs were associated with cell signaling pathways in cancer development. This review focuses on the composition, cargo, function, mechanism, and application of EVs in cancers.

A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis.

Long noncoding RNAs (lncRNAs) show emerging roles in colorectal cancer (CRC) development and are considered to be involved in the potential mechanism of tumor malignancy. While Sox2 overlapping transcript (SOX2OT) has been implicated in the progression of multiple cancers, its role in CRC remains to be explored. In this study, in situ hybridization (ISH) and qRT-PCR were performed to establish the functional relationships between SOX2OT and CRC deranged in CRC tissue and cells. Subsequently, SOX2OT shRNAs vectors were transfected into CRC cells to performed loss-of-function assays to detect the potential role of SOX2OT on proliferation and metastasis in vitro and vivo. The results showed SOX2OT was an oncogene that was up-regulated in human CRC tissues and cell lines. SOX2OT silencing suppressed cell proliferation, migration, and invasion in CRC cells in vitro, and inhibited tumorigenesis in the mouse xenografts. Bioinformatic predictive analysis coupled with the dual-luciferase reporter, RNA immunoprecipitation (RIP), and functional rescue assay elucidated the mechanistic network of the SOX2OT-miR-194-5p-SOX5 axis in CRC. Mechanistically, SOX2OT acted as a competing endogenous RNA (ceRNA) to upregulate SOX5 by sponging miR-194-5p. Downregulated SOX2OT boosted miR-194-5p expression, thus decreased the protein level of SOX5, which suppresses tumorgenesis of CRC.

The Role and Application of Exosomes in Gastric and Colorectal Cancer.

Gastric cancer and colorectal cancer are malignant tumors found in the human gastrointestinal tract. Bidirectional communication between tumor cells and their microenvironment can be realized through the transmission of exosomes-small, cell-derived vesicles containing complex RNA and proteins. Exosomes play an important role in the proliferation, metastasis, immune response, and drug resistance of cancer cells. In this review, we focus on the role and application of exosomes in gastric and colorectal cancer. We also summarize the role of exosomes secreted by different types of cells in tumor development and as drug carriers in cancer treatment.

Integrated metabolomics and network pharmacology approach to reveal immunomodulatory mechanisms of Yupingfeng granules.

Systems biology is an approach that employs modern biological techniques and methods to combine the overall regulation of the body by Chinese herbal formulas with systems analysis at the molecular level. In this study, the underlying immunomodulatory mechanisms of yupingfeng granules (YPFG) were investigated based on the integration of metabolomics and network pharmacology methods. Selected routine peripheral blood indicators, body weight, and organ indices related to immunity were firstly measured in order to evaluate the effects of YPFG in cyclophosphamide-induced immunocompromised rats. Plasma metabolomics analyses were carried out by UPLC-Q-TOF-MS combined with a multivariate data analysis. Our study indicates that the potential regulatory mechanism was related to bile acid and glycerophospholipid metabolism, involving the regulation of 11 metabolites, including 8 bile acids, 1 phosphatidylserine, and 2 phosphatidylethanolamines. By means of network pharmacology, the compound-target network between potential active components of YPFG and immune dysregulation was constructed, which releated to estrogen receptor, PPAR, MAPK, PI3K-Akt, JNK signaling pathways, and ubiquitin-mediated protein degradation. The immunomodulatory effect of YPFG may be exerted through regulating lipid metabolism, then bile acid metabolism and inflammation were affected. Biological verification was also performed on cyclophosphamide-induced immunocompromised BALB/c mice. Flavonoid and saponin, two types of compounds in YPFG, were found to be the major active ingredients in the immunomodulatory effects of YPFG, and these components may regulate the abnormal metabolism of bile acids by enhancing the expression of FXR and LXRα. This work elucidated active ingredients, potential biomarkers, and mechanisms of action in the immunoregulatory effects of YPFG from the perspective of systems biology, which provides a scientific basis for its precise clinical medication.

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.

Ileocolic intussusception caused by ileal lipoma: A case report.

RATIONALE: Adult intussusception is rarely observed, accounting for about 5% of all cases of intussusception. Most ileal lipomas are asymptomatic and do not need any special treatment. Herein, we describe a case with ileocolic intussusception caused by ileal lipoma. PATIENT CONCERNS: A 27-year-old woman complaints of intermittent abdominal pain for 10 days. DIAGNOSIS: Abdominal computed tomography demonstrated ileocolic intussusception. Colonoscopy revealed a spherical polypoid lesion with surface capillary rising from the lateral wall of the ileum. A diagnosis of ileocolic intussusception was made. INTERVENTIONS: The patient underwent primary resection of the intussuscepted intestine after which an end-to-end anastomosis was performed. OUTCOMES: Histopathology report confirmed a 4.5 cm × 3.5 cm lipoma in the terminal ileum. The patient was discharged on a postoperative day 9 without complications. LESSONS: We describe the difficulties in diagnosis and treatment of this rare cause of intussusception and review the literature on adult intussusceptions. The ileal lipoma is a very rare cause of ileocolic intussusception. Abdominal CT and colonoscopy are important for the diagnosis of intussusception and abdominal lipomas. Surgical resection remains the treatment of choice.