Current knowledge of anthocyanin metabolism in the digestive tract: absorption, distribution, degradation, and interconversion.

Potential roles for anthocyanins in preventing various chronic diseases have been reported. These compounds are highly sensitive to external conditions and are susceptible to degradation, which increases the complexity of their metabolism in vivo. This review discusses anthocyanin metabolism in the digestive tract, phase I and II metabolism, and enterohepatic circulation (EHC), as well as their distribution of anthocyanins in blood, urine, and several organs. In the oral cavity, anthocyanins are partly hydrolyzed by microbiota into aglycones which are then conjugated by glucuronidase. In stomach, anthocyanins are absorbed without deglycosylation via specific transporters, such as sodium-dependent glucose co-transporter 1 and facilitative glucose transporters 1, while in small intestine, they are mainly absorbed as aglycones. High polymeric anthocyanins are easily degraded into low-polymeric forms or smaller phenolic acids by colonic microbiota, which improves their absorption. Anthocyanins and their derivatives are modified by phase I and II metabolic enzymes in cells and are released into the blood via the gastrovascular cavity into EHC. Notably, interconversion can be occurred under the action of enzymes such as catechol-O-methyltransferase. Taking together, differences in anthocyanin absorption, distribution, metabolism, and excretion largely depend on their glycoside and aglycone structures.

Synergistic effect of siRNA-mediated silencing of TGF-ß R1 and TGF-ß R2 genes on the proliferation and apoptosis of penile urethral epithelial cells in hypospadiac male rats.

The study elucidated the effects associated with silencing growth factor-ß R1 (TGF-ß R1) and TGF-ß R2 genes on the proliferation and apoptosis of penile urethral epithelial cells (UECs) in hypospadiac male rats. Seventy-five male rats were distributed into the normal, model, TGF-ß R1/2-siRNA, TGF-ß R1-siRNA and TGF-ß R2-siRNA groups. The UECs of the rats included in the study were cultured in vitro and subsequently divided into the control, blank, TGF-ß R1/2-siRNA, TGF-ß R1-siRNA and TGF-ß R2-siRNA groups. The mRNA and protein expressions of TGF-ß R1/R2 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Cell proliferation and apoptosis were evaluated by cell counting kit-8 (CCK-8) assay as well as by flow cytometry. Compared with the normal group, the apoptotic rate of the UECs in the model, TGF-ß R1/2-siRNA, TGF-ß R1-siRNA and TGF-ß R2-siRNA groups displayed remarkable increases; compared with the model group, the apoptotic rate of the UECs in the TGF-ß R1/2-siRNA, TGF-ß R1-siRNA and TGF-ß R2-siRNA groups displayed significant decreases, similar observations were made regarding mRNA and protein expressions of TGF-ß R1 and TGF-ß R2. Compared with the TGF-ß R1/2-siRNA group, the apoptotic rates of the UECs in the TGF-ß R1-siRNA and TGF-ß R2-siRNA groups were up regulated, while cell proliferation in the TGF-ß R1-siRNA and TGF-ß R2-siRNA groups decreased accompanied by an increased rate of apoptosis. This study ultimately demonstrated that the silencing of TGF-ß R1 and TGF-ß R2 genes could promote cell proliferation and inhibit apoptosis of penile UECs in hypospadiac male rats.

Expression of nestin in embryonic tissues and its effects on clinicopathological characteristics of patients with placenta previa.

In this study, we examined expression of nestin in the spinal cord, lung, kidney, stomach, colon, and intestine tissues at different stages of embryos in patients with placenta previa. Fetuses of 75 patients with placenta previa were assigned to case group and 80 fetuses from healthy pregnant women with normal placenta who voluntarily terminated pregnancy to control group. Clinical data of pregnant women were collected at the time of admission. Blood from elbow vein was collected to determine expression of serum nestin. Tissues from spinal cord, lung, kidney, stomach, colon, and intestine in 3-7 months fetuses of the two groups were extracted. Expression of nestin in tissues was detected by immunohistochemistry, Western blotting and RT-qPCR. The mRNA expression of nestin in the case group was increased. Nestin expression was correlated with the gestational age, age of foetus, and type of placenta previa in patients with placenta previa. Positive nestin expression was detected in the spinal cord, lung, kidney, stomach, intestine, and colon tissues in normal and placenta previa embryo at Stage I. The positive cell density and nestin expression decreased at Stage II, and further decreased at Stage III. The case group had higher nestin mRNA and protein levels throughout human fetal development. Findings of this study suggested that, nestin, as a specific marker of neural precursor cells, was expressed in various tissues of the embryo in patients with placenta previa and nestin expression was lower with increased maturation of the embryo.

Long noncoding RNA HULC modulates the phosphorylation of YB-1 through serving as a scaffold of extracellular signal-regulated kinase and YB-1 to enhance hepatocarcinogenesis.

Dysregulated expression of long noncoding RNAs has been reported in many types of cancers, indicating that it may play a critical role in tumorigenesis. The long noncoding RNA highly up-regulated in liver cancer (HULC) was first characterized in hepatocellular carcinoma. However, the detailed mechanisms of HULC remain unclear. Here, we demonstrate a novel mechanism by which long noncoding RNA plays oncogenic roles through modulating the phosphorylation status of its interaction protein. First, we validated the markedly increased expression levels of HULC in hepatocellular carcinoma tissues compared to their adjacent noncancerous tissues. Furthermore, up-regulation of HULC was correlated with grading and overall survival. Meanwhile, HULC could promote cell proliferation, migration, and invasion in vitro and inhibit cisplatin-induced apoptosis. Moreover, we show that HULC specifically binds to Y-box binding protein 1 (YB-1) protein both in vitro and in vivo. YB-1 is a major component of translationally inactive messenger ribonucleoprotein particles which keeps mRNA in a silent state. Our study further demonstrated that HULC could promote the phosphorylation of YB-1 protein, which leads to the release of YB-1 from its bound mRNA. As a consequence, translation of silenced oncogenic mRNAs would be activated, including cyclin D1, cyclin E1, and matrix metalloproteinase 3. In addition, we found that HULC promotes the phosphorylation of YB-1 protein mainly through extracellular signal-regulated kinase. CONCLUSION: We demonstrate that HULC promotes the phosphorylation of YB-1 through the extracellular signal-regulated kinase pathway, in turn regulates the interaction of YB-1 with certain oncogenic mRNAs, and consequently accelerates the translation of these mRNAs in the process of tumorigenesis. (Hepatology 2017;65:1612-1627).

Differential Expression of miR-34c and Its Predicted Target Genes in Testicular Tissue at Different Development Stages of Swine.

To verified the target genes of miR-34c, bioinformatics software was used to predict the targets of miR-34c. Three possible target genes of miR-34c related to spermatogenesis and male reproductive development: zinc finger protein 148 (ZNF148), kruppel-like factor 4 (KLF4), and platelet-derived growth factor receptor alpha (PDGFRA) were predicted. Then, the expression of miR-34c and its target genes were detected in swine testicular tissue at different developmental stages by quantitative polymerase chain reaction. The results suggested that the expression of PDGFRA has the highest negative correlation with miR-34c. Then immunohistochemical staining was done to observe the morphology of swine testicular tissue at 2-days and 3, 4, 5-months of age, which indicated that PDGFRA was mainly expressed in the support cells near the basement membrane during the early development stages of testicular tissue, but that the expression of PDGFRA was gradually reduced in later stages. Therefore, western blot analyzed that the highest expression of PDGFRA was generated in 2-days old testicular tissues and the expression levels reduced at 3 and 4-months old, which correlated with the results of immunohistochemical staining. In conclusion, PDGFRA is a target gene of miR-34c.

Symptom experiences and influencing factors in patients undergoing chemotherapy for gastrointestinal cancers: a qualitative study.

Objective: To explore the symptom experiences and influencing factors of gastrointestinal (GI) cancer patients on chemotherapy (CTX) in China. Methods: Semi-structured interviews were conducted with 13 GI cancer patients undergoing CTX. Following the Colaizzi 7-step analysis method, the interview data were read carefully, meaningful statements related to the research questions were extracted, coded, collected, and described in detail, and the authenticity of the theme was verified. Results: Nine themes were grouped into two main areas including the characteristics of symptom experiences and influences on symptom experiences. Conclusion: The symptom experiences of patients undergoing CTX for GI cancer is poor and influenced by multiple factors. Nurses need to pay attention to the assessment and monitoring of CTX-related symptoms, improve symptom recognition, enhance doctor-patient communication and social support, explore intelligent management methods, and increase the efficiency of healthcare services to improve patients' symptom experience.

Structural characterization, antioxidant and antibacterial activity of three pectin polysaccharides from blueberry.

In this study, three pectin polysaccharides BP1, BP2 and BP3, were purified from blueberries. The weight-average molecular weight (Mw) of BP1, BP2, and BP3 were detected to be 9.027 × 104, 9.313 × 104, and 1.223 × 106 Da, respectively. The structures of the three pectin polysaccharides were characterized and compared based on the results of molecular weight, monosaccharide composition, GC-MS and NMR analysis. Structural characterization revealed that BP1, BP2, and BP3 all contain homogalacturonan (HG) and rhamnogalacturonan I (RG-I) domains, and the rhamnose residues in RG-I domains are substituted at C-4 with side chains such as araban and galactosan. BP2 had the highest degree of esterification and HG domain ratio, followed by BP3 and BP1. In addition, BP1, BP2 and BP3 showed great antioxidant and antibacterial activities, and could destroy the cell membrane of Staphylococcus aureus and Escherichia coli. Moreover, the better DPPH and ABTS free radical scavenging and antibacterial activities of BP1 and BP2 than BP3 might be related to their lower molecular weight. The results of this study will provide essential information for the structure-activity relationship of pectin polysaccharides and research basis for development and application of blueberry pectin polysaccharides.

Placental vessel segmentation and registration in fetoscopy: Literature review and MICCAI FetReg2021 challenge findings.

Fetoscopy laser photocoagulation is a widely adopted procedure for treating Twin-to-Twin Transfusion Syndrome (TTTS). The procedure involves photocoagulation pathological anastomoses to restore a physiological blood exchange among twins. The procedure is particularly challenging, from the surgeon's side, due to the limited field of view, poor manoeuvrability of the fetoscope, poor visibility due to amniotic fluid turbidity, and variability in illumination. These challenges may lead to increased surgery time and incomplete ablation of pathological anastomoses, resulting in persistent TTTS. Computer-assisted intervention (CAI) can provide TTTS surgeons with decision support and context awareness by identifying key structures in the scene and expanding the fetoscopic field of view through video mosaicking. Research in this domain has been hampered by the lack of high-quality data to design, develop and test CAI algorithms. Through the Fetoscopic Placental Vessel Segmentation and Registration (FetReg2021) challenge, which was organized as part of the MICCAI2021 Endoscopic Vision (EndoVis) challenge, we released the first large-scale multi-center TTTS dataset for the development of generalized and robust semantic segmentation and video mosaicking algorithms with a focus on creating drift-free mosaics from long duration fetoscopy videos. For this challenge, we released a dataset of 2060 images, pixel-annotated for vessels, tool, fetus and background classes, from 18 in-vivo TTTS fetoscopy procedures and 18 short video clips of an average length of 411 frames for developing placental scene segmentation and frame registration for mosaicking techniques. Seven teams participated in this challenge and their model performance was assessed on an unseen test dataset of 658 pixel-annotated images from 6 fetoscopic procedures and 6 short clips. For the segmentation task, overall baseline performed was the top performing (aggregated mIoU of 0.6763) and was the best on the vessel class (mIoU of 0.5817) while team RREB was the best on the tool (mIoU of 0.6335) and fetus (mIoU of 0.5178) classes. For the registration task, overall the baseline performed better than team SANO with an overall mean 5-frame SSIM of 0.9348. Qualitatively, it was observed that team SANO performed better in planar scenarios, while baseline was better in non-planner scenarios. The detailed analysis showed that no single team outperformed on all 6 test fetoscopic videos. The challenge provided an opportunity to create generalized solutions for fetoscopic scene understanding and mosaicking. In this paper, we present the findings of the FetReg2021 challenge, alongside reporting a detailed literature review for CAI in TTTS fetoscopy. Through this challenge, its analysis and the release of multi-center fetoscopic data, we provide a benchmark for future research in this field.

The recent advance of Interleukin-1 receptor associated kinase 4 inhibitors for the treatment of inflammation and related diseases.

The interleukin-1 receptor associated kinase 4 (IRAK-4) is a member of serine-threonine kinase family, which plays an important role in the regulation of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs) related signaling pathways. At present, the IRAK-4 mediated inflammation and related signaling pathways contribute to inflammation, which are also responsible for other autoimmune diseases and drug resistance in cancers. Therefore, targeting IRAK-4 to develop single-target, multi-target inhibitors and proteolysis-targeting chimera (PROTAC) degraders is an important direction for the treatment of inflammation and related diseases. Moreover, insight into the mechanism of action and structural optimization of the reported IRAK-4 inhibitors will provide the new direction to enrich the clinical therapies for inflammation and related diseases. In this comprehensive review, we introduced the recent advance of IRAK-4 inhibitors and degraders with regards to structural optimization, mechanism of action and clinical application that would be helpful for the development of more potent chemical entities against IRAK-4.

[Advances in the Study of Tumor-associated Macrophages in Lung Cancer].

Lung cancer is one of the malignant tumors with the highest morbidity and mortality in China. Therefore, the research on the treatment of lung cancer is also deepening. At present, there are mainly systemic chemotherapy, targeted therapy for positive driver genes, the application of immune checkpoint inhibitors, anti-tumor angiogenesis therapy and the combination of the different treatment methods mentioned above. The use of these regimens has significantly improved the prognosis of most lung cancer patients, but the prognosis of patients with advanced lung cancer remains unsatisfactory. Recently, more and more attention has been paid to the study of tumor microenvironment (TME). TME consists of immune cells, fibroblasts, vascular endothelial cells and other cellular components as well as related cytokines, which is the basis for the survival and development of tumor cells. As an important immune cell of TME, tumor-associated macrophages (TAMs) refer to macrophages infiltrating in tumor tissues, which can promote tumor cell proliferation, induce tumor immune tolerance, stimulate tumor angiogenesis, and increase the invasion and metastasis ability of tumor cells. Therefore, targeting TAMs has become a hot topic in lung cancer immunotherapy. In this review, the sources, phenotypes, mechanisms of TAMs in lung cancer, as well as future therapeutic targets of TAMs were reviewed to provide reference for optimal treatment of lung cancer.
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Antiviral activities of Radix isatidis polysaccharide against pseudorabies virus in swine testicle cells.

BACKGROUND: Radix isatidis has been used in China and other Asian countries for its antiviral and anti-inflammatory effects for thousands of years. However, the antiviral effect of Radix isatidis polysaccharide against pseudorabies virus (PRV) is still unknown. METHODS: The polysaccharide were isolated from extract of the roots of Radix isatidis. MTT assays were used to determine the preventive effect, inhibitory effect and antiviral effect of Radix isatidis polysaccharide on PRV in vitro. RESULTS: This study found that different concentrations of polysaccharides from this plant can inhibit PRV replication by 14.674-30.840%, prevent infection at rates of 6.668-14.923%, and kill this virus at rates of 32.214-67.422%. CONCLUSION: These results broaden the understanding of this traditional Chinese herb and provide a theoretical basis for further research. Moreover, Radix isatidis polysaccharide could be used for antiviral therapy.

Clinical investigation of acute myocardial infarction according to age subsets.

A growing number of 'Young' patients less than 40 years of age are being hospitalized with a diagnosis of acute myocardial infarction (AMI) due to increased prevalence of risk factors for atherosclerosis. The aim of this study was to compare clinical characteristics and performances of AMI between young and elderly patients. We conducted a retrospective study to compare AMI in young patients and elder patients. Based on the medical record databases in our hospital, we enrolled 114 'young' AMI patients (age ≤42 years) and 179 'elder' AMI patients (≥60 years), and then collected and analyzed their demographic information, clinical performances, and coronary angiography results. In the young AMI group, the proportion of male patients was higher than that in the elder AMI group (94.7 vs. 64.2%, P<0.05). Compared with the elder AMI patients, young patients had higher rates of smoking history and positive family medical history, but lower rates of hypertension and diabetes. Elder patients with AMI were more likely to develop various clinical performances, and multiple-branch lesions; however, young AMI patients had relatively fewer symptoms, and the tissue lesions were more limited. The clinical profiles of AMI in young patients were different from that in elder AMI patients. Specific interventions should be carried out to prevent and control the prevalence of AMI in the young population.

Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells.

EGCG [(-)-epigallocatechin-3-gallate] has shown its antitumor ability and perhaps a potential regimen for cancer patients. The goal of this study was to investigate the effect of EGCG on human papilloma virus (HPV) positive cervical cancer cell lines. EGCG inhibited the growth of CaSki (HPV16 positive) and HeLa (HPV18 positive) cells in a time- and concentration-dependent manner. Cell cycle arrest and apoptosis were observed in two cell lines after EGCG exposure. More importantly, we focused on EGCG regulation ability on pivotal genes involved in cervical cancer: viral oncogenes E6/E7, estrogen receptor (ER) and aromatase. Our results suggested that EGCG may be suitable for prevention and treatment of cervical cancer.