Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective.

The highly conserved Notch signaling pathway affects embryonic development, neurogenesis, homeostasis, tissue repair, immunity, and numerous other essential processes. Although previous studies have demonstrated the location and function of the core components of Notch signaling in various animal phyla, a more comprehensive summary of the Notch core components in lower organisms is still required. In this review, we objectively summarize the molecular features of the Notch signaling pathway constituents, their current expression profiles, and their functions in invertebrates, with emphasis on their effects on neurogenesis and regeneration. We also analyze the evolution and other facets of Notch signaling and hope that the contents of this review will be useful to interested researchers.

Study on Psychological Stress Response and Intervention Countermeasures of Exposed Population under Sudden Public Health Crisis.

Background: After the occurrence of public health emergencies, people will have a series of physiological reactions, which will develop into psychological stress disorder in serious cases. Based on this, the purpose of this study is to analyze the psychological stress response and intervention countermeasures of exposed people under sudden public health crisis. Objective: To explore the psychological stress response and intervention countermeasures of exposed population under sudden public health crisis. Methods: A total of 400 people under the sudden public health crisis that bring about serious damage to public health, mass diseases of unknown causes, major food and occupational poisoning, and other events that seriously affect public health from December 2020 to December 2021 were selected as the subjects of the study. It was randomly and equally divided into two groups to take different intervention measures, the control group was given routine public health crisis intervention measures, and the research group was given comprehensive intervention. The metabolism, social function defects, health symptoms, psychological status, quality of life, sleep quality, and stress reaction were compared between the two groups. Results: The rate of good metabolism in the research group was significantly higher than that in the control group (P < 0.05). After intervention, the scores of Social Disability Screening Schedule (SDSS) and Symptom Checklist 90 (SCL-90) decreased in both groups, and the scores of SDSS and SCL-90 in the research group were lower than those in the control group. After intervention, the scores of self-rating depression scale and self-rating anxiety scale in the two groups decreased, and the scores of self-rating depression scale and self-rating anxiety scale in the research group were lower than those in the control group (P < 0.05). The sleep quality of the research group was better than that of the control group (P < 0.05). The stress response indexes such as cortisol, blood glucose, and C-reactive protein in the two groups were decreased after intervention. The stress response indexes such as cortisol, blood glucose, and C-reactive protein in the research group were lower than those in the control group (P < 0.05). Conclusion: Giving that comprehensive intervention measures to people exposed to sudden public health crisis can effectively relax their stress response, reinvigorate their quality of life and sleep, reduce depression and anxiety, and improve their metabolism, therefore, in the case of the outbreak of public health crisis in the future, it is worth applying for reference and popularizing.

Tumor microenvironment contributes to Epstein-Barr virus anti-nuclear antigen-1 antibody production in nasopharyngeal carcinoma.

Nuclear antigen-1 (NA1) protein of Epstein-Barr virus (EBV) is expressed in EBV-infected cells in the microenvironment of cancer. Since immune cells infiltrate abundantly in nasopharyngeal carcinoma (NPC) tumor tissues, we hypothesized that the local tumor microenvironment may perform an important role in the production of antibodies directed at NA1. Furthermore, we hypothesized that anti-NA1 antibody originating in the local microenvironment could be secreted into the saliva of patients with NPC. In the present study, 20 healthy controls and 39 patients with NPC treated with intensity-modulated radiation therapy were recruited for the study. Saliva and serum samples were collected from the NPC patients, and nasopharyngeal tissue samples from the patients with NPC. The titers of anti-NA1 antibody [immunoglobulin A (IgA)] were determined by ELISA. Expression of NA1, human leukocyte antigen-antigen D related (HLA-DR), cluster of differentiation (CD)80, CD86, CD3, CD4, CD19 and IgA was detected by immunohistochemical staining on paraffin-embedded nasopharyngeal tissue sections. Anti-NA1 antibodies were detected in the serum and saliva samples of the patients with NPC. In infiltrating cells, expression of HLA-DR, CD80, CD86, CD3, CD4, CD19 and IgA was detected, indicating that dendritic cells, T lymphocytes and B lymphocytes were all present in the local tumor tissues. Furthermore, expression of EBNA1 protein was detected on the membrane of the NPC tumor cells. Therefore, the NPC tumor microenvironment has the potential to initiate a humoral response to EBNA1 by producing IgA antibodies.

Elevation of urinary adipsin in preeclampsia: correlation with urine protein concentration and the potential use for a rapid diagnostic test.

Early diagnosis and treatment of preeclampsia are essential for prevention of seizure development and fetus maturation. Although various methods have been developed for predicting or monitoring the onset of preeclampsia, a simple assay that can be used as a home or point of care test remains unavailable. We attempted to find a urinary protein that could be used as a biomarker for developing such a test. Urinary samples were collected from 124 preeclampsia and 135 healthy pregnant women for screening using a protein array technology and quantification by ELISA. A urinary protein, adipsin, was found significantly increased, and the adipsin creatinine ratio was closely correlated with the urinary 24-hour protein in patients with preeclampsia. When combined with the increased diastolic blood pressure (≥90 mm Hg), the sensitivity was 90.3% and the specificity reached 100.0% for preeclampsia diagnosis. We then developed a laminar flow immunoassay for rapid diagnosis, and the sensitivity and specificity were 89.04% and 100%, respectively, when combined with increased diastolic blood pressure. Because of the easiness of sample collection, assay conduction, and result interpretation, this urine test can be potentially used as a home test for monitoring preeclampsia onset for high-risk pregnant women and as a rapid test for a preliminary diagnosis for emergency patients at hospitals.

Bioactive proteins in healthy pregnancies and preeclampsia: relevance to hypertension and proteinuria.

BACKGROUND: Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia. METHODS: Samples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay. RESULTS: Interleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preeclampsia patients. In particular, interleukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients. CONCLUSIONS: Because of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.

Association between polymorphisms in the promoter region of miR-143/145 and risk of colorectal cancer.

Emerging evidence suggests that down-regulated miRNAs play an important role in the carcinogenesis of colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) in the promoter region of miRNAs may disturb miRNAs processing, alter their expression, and ultimately affect an individual's susceptibility to CRC. We conducted a case-control study and analyzed twelve SNPs in the promoter region of miR-143/145 of 525 subjects including 242 cases with CRC and 283 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The mutant genotypes or alleles of rs41291957, rs353292, rs353293, and rs4705341 were significantly associated with an increased risk of CRC compared with the wild genotypes or alleles, while rs4705343, rs17796757, rs3733845, and rs3733846 were significantly associated with a decreased risk of CRC. When stratification analysis was done by different variables, such as tumor size, tumor site, differentiated status, clinical stage, and metastasis status, we found that patients with the mutant allele of rs41291957 had an increased risk to develop a tumor size larger than 5 cm. These findings suggest that SNPs in the promoter region of miR-143/145 may be related to the etiology of CRC. However, further larger studies with different ethnic origins are needed to confirm our results due to limited sample sizes in the study.

Clinical evaluation of soluble intercellular adhesion molecule-1 and insulin like growth factor-binding protein-1-based rapid immunoassays for the diagnosis of prelabor rupture of membranes.

AIMS: To evaluate the clinical value of two rapid tests, based on soluble intercellular adhesion molecule-1 (Leakection) and insulinlike growth factor-binding protein-1 (Amnioquick), for the diagnosis of prelabor rupture of membranes. METHODS: A total of 200 pregnant women were recruited in this study: 100 pregnant women with membrane rupture and 100 healthy pregnant women as controls. Patients and controls were randomly divided into Leakection and Amnioquick groups, respectively. Sensitivity and specificity were calculated on the basis of the detection results. RESULTS: For the 100 women tested with Leakection, the sensitivity and specificity was 94% and 96%, respectively; the total accuracy was 95%. For the 100 women tested with Amnioquick, the sensitivity and specificity was 80% and 100%, respectively; the total accuracy was 90%. CONCLUSIONS: Both Leakection and Amnioquick are noninvasive and inexpensive rapid tests for the diagnosis of premature or prelabor rupture of membranes with high sensitivity and specificity. These tests could greatly help the timely diagnosis of premature or prelabor rupture of membranes in clinical practice.

Determination of antibodies directed at EBV proteins expressed in both latent and lytic cycles in nasopharyngeal carcinoma.

OBJECTIVES: Serologic analyses for anti-EBV antibodies used alone usually have low sensitivity for the diagnosis of nasopharyngeal carcinoma (NPC). We assumed that a combined determination of antibodies directed at EBV proteins expressed in both lytic and latent cycles could increase the sensitivity. MATERIALS AND METHODS: Sixty healthy controls and 100 NPC patients treated with intensity-modulated radiation therapy were recruited for the study. Serial blood samples of NPC patients were collected before, during and after the treatment. The titers of antibodies directed at Rta (IgG), EA (IgG), VCA (IgA), and NA1 (IgA) were determined in duplicate by ELISA. RESULTS: Results showed that the combined tests of EA and Rta antibodies significantly improved the sensitivity from 89.0% for EA alone to 95%. For VCA or NA1 in combination with the EA test, it was revealed that either the increase of the specificity was minimal, or the decrease of the specificity was unacceptable. Rta, EA, VCA, and NA1 antibody titers in serial samples were followed from 53 patients of complete remission and 9 patients with recurrence or distal metastasis post the treatment for 2 years. However, the trend of antibody titers of Rta, VCA or NA1 in combination with EA failed to indicate a difference between patients with good and poor prognosis. CONCLUSION: Combined measurements of anti-Rta and anti-EA antibodies could significantly increase the sensitivity for the diagnosis of NPC while maintain a high specificity.