Tak1 is Required for the Survival of Hematopoietic Cells and Hepatocytes in Mice

Transforming growth factor beta-activated kinase 1 (TAK1), a member of the MAPKKK family, is a key mediator of proinflammatory and stress signals. Activation of TAK1 by proinflammatory cytokines and T and B cell receptors induces the nuclear localization of nuclear factor kappaB (NF-kappaB) and the activation of c-Jun N-terminal kinase (JNK)/AP1 and P38, which play important roles in mediating inflammation, immune responses, T and B cell activation, and epithelial cell survival. Here, we report that TAK1 is critical for the survival of both hematopoietic cells and hepatocytes. Deletion of TAK1 results in bone marrow (BM) and liver failure in mice due to the massive apoptotic death of hematopoietic cells and hepatocytes. Hematopoietic stem cells and progenitors were among those hematopoietic cells affected by TAK1 deletion-induced cell death. This apoptotic cell death is autonomous, as demonstrated by reciprocal BM transplantation. Deletion of TAK1 resulted in the inactivation of both JNK and NF-kappaB signaling, as well as the down-regulation of expression of prosurvival genes

Dynamic profiling of intact glucosinolates in radish by combining UHPLC-HRMS/MS and UHPLC-QqQ-MS/MS

Glucosinolates (GSLs) and their degradation products in radish confer plant defense, promote human health, and generate pungent flavor. However, the intact GSLs in radish have not been investigated comprehensively yet. Here, an accurate qualitative and quantitative analyses of 15 intact GSLs from radish, including four major GSLs of glucoraphasatin (GRH), glucoerucin (GER), glucoraphenin (GRE), and 4-methoxyglucobrassicin (4MGBS), were conducted using UHPLC-HRMS/MS in combination with UHPLC-QqQ-MS/MS. Simultaneously, three isomers of hexyl GSL, 3-methylpentyl GSL, and 4-methylpentyl GSL were identified in radish. The highest content of GSLs was up to 232.46 μmol/g DW at the 42 DAG stage in the ‘SQY’ taproot, with an approximately 184.49-fold increase compared to the lowest content in another sample. That the GSLs content in the taproots of two radishes fluctuated in a similar pattern throughout the five vegetative growth stages according to the metabolic profiling, whereas the GSLs content in the ‘55’ leaf steadily decreased over the same period. Additionally, the proposed biosynthetic pathways of radish-specific GSLs were elucidated in this study. Our findings will provide an abundance of qualitative and quantitative data on intact GSLs, as well as a method for detecting GSLs, thus providing direction for the scientific progress and practical utilization of GSLs in radish

Protective Effect of 18 β

Triptolide (TP) is the major active component of Tripterygium wilfordii Hook F (TWHF) and possesses multiple pharmacological effects. However, hepatotoxicity of TP which is one of the toxic properties slows its progression in clinical application. 18β-Glycyrrhetinic acid (GA) is the main bioactive ingredient of Licorice (Glycyrrhiza glabra L.), a herbal medicine famous for its detoxification. This study aims to investigate whether GA possesses protective effect against TP-induced hepatotoxicity in rats. TP interference markedly elevated serum levels of ALT, AST, and ALP, caused evident liver histopathological changes, and elevated hepatic TNF-α, IL-6, IL-1β, and IFN-γ as well as nuclear translocation of NF-κB. TP also significantly elevated liver MDA and declined hepatic activities of SOD, CAT, and GSH-Px. Assay of TUNEL and apoptosis proteins (Bax, Bcl-2, and active caspase-3) showed that TP induced severe hepatocellular apoptosis. In contrast, low-dose GA (50 mg/kg) significantly reversed TP-induced changes above. However, high-dose GA (100 mg/kg) had no such effect. Overall, these findings indicated that low-dose GA but not high-dose GA exhibited a protective effect against TP-induced hepatotoxicity in rats by anti-inflammation, antioxidation, and antiapoptosis, which suggests that the doses of GA/Licorice should be carefully considered when used together with TWHF or TWHF preparations

Hsf transcription factor gene family in peanut (Arachis hypogaea L.): genome-wide characterization and expression analysis under drought and salt stresses

Heat shock transcription factors (Hsfs) play important roles in plant developmental regulations and various stress responses. In present study, 46 Hsf genes in peanut (AhHsf) were identified and analyzed. The 46 AhHsf genes were classed into three groups (A, B, and C) and 14 subgroups (A1-A9, B1-B4, and C1) together with their Arabidopsis homologs according to phylogenetic analyses, and 46 AhHsf genes unequally located on 17 chromosomes. Gene structure and protein motif analysis revealed that members from the same subgroup possessed similar exon/intron and motif organization, further supporting the results of phylogenetic analyses. Gene duplication events were found in peanut Hsf gene family via syntenic analysis, which were important in Hsf gene family expansion in peanut. The expression of AhHsf genes were detected in different tissues using published data, implying that AhHsf genes may differ in function. In addition, several AhHsf genes (AhHsf5, AhHsf11, AhHsf20, AhHsf24, AhHsf30, AhHsf35) were induced by drought and salt stresses. Furthermore, the stress-induced member AhHsf20 was found to be located in nucleus. Notably, overexpression of AhHsf20 was able to enhance salt tolerance. These results from this study may provide valuable information for further functional analysis of peanut Hsf genes

Influencing factors for esophageal stenosis caused by sclerotherapy for esophageal varices

ObjectiveTo investigate the influencing factors for esophageal stenosis caused by sclerotherapy for esophageal varices. MethodsA retrospective analysis was performed for the clinical data of 17 patients with esophageal stenosis caused by sclerotherapy for esophageal varices who were treated in Beijing You′an Hospital from February 2011 to December 2016, and 17 patients who were given sclerotherapy for esophageal varices and did not experience esophageal stenosis were enrolled as control group. The two groups were compared in terms of dose of sclerosing agent, number of treatments, injection site, and other related factors. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsThe esophageal stenosis group had a significantly lower number of treatments with sclerosing agent than the control group (3.11±0.90 vs 5.12±2.11, t=-3267, P=0.003). Compared with the control group, the esophageal stenosis group had significantly higher total dose of sclerosing agent (36.12±3.55 ml vs 28.36±5.08 ml, t=4.046, P＜0.001) and dose of sclerosing agent for last injection (19.13±4.19 ml vs 12.46±2.61 ml, t=4.179, P＜0.001), and the injection sites were close to each other or located on the same plane. Repeated sclerotherapy caused esophageal stenosis in case of improper operation. ConclusionIt is of great clinical significance to properly determine injection dose, site, and number of injections and avoid overlap between ulcers, in order to prevent esophageal stenosis after sclerotherapy for esophageal varices

Outcome Evaluation in Social Context Measured by Event-Related Potentials Is Partially Dependent on the Partner’s Sex

Outcome evaluation is a cognitive process that people rely on feedback information to evaluate behavior results. It can help people to modify the previous mistakes in order to facilitate the performance of the behavior. In the present study, we examined sex differences in outcome evaluation when men and women performed a “Chuck-A-Luck” dice game with a same-versus opposite-sex partner. We recruited 40 college students (Half of women) to perform the gambling game task, and event-related potentials (ERPs) were recorded for outcome feed back when male or female participants performed the game alone, or with same-versus opposite-sex partners. Two main findings are reported in our study. (1) FRN amplitude of same-sex condition was significantly greater than alone condition for male when the feedback was loss. However, FRN amplitude of opposite-sex condition was significantly greater than alone condition for female when feedback was loss. (2) The loss feedback induced greater P300 than gain only in alone condition. It suggests that sex differences in outcome evaluation is a complex process that is partially influenced by the partner’s sex

Bioactive natural compounds against human coronaviruses: a review and perspective

Coronaviruses (CoVs), a family of enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, unusually large RNA genome, and unique replication capability. CoVs are known to cause various potentially lethal human respiratory infectious diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the very recent coronavirus disease 2019 (COVID-19) outbreak. Unfortunately, neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs. Therefore, effective prevention and treatment medications against human coronavirus are in urgent need. In the past decades, many natural compounds have been reported to possess multiple biological activities, including antiviral properties. In this article, we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS, and discussed their potential use for the treatment of COVID-19

IFN-τ Displays Anti-Inflammatory Effects on Staphylococcus aureus Endometritis via Inhibiting the Activation of the NF-κB and MAPK Pathways in Mice

The aim of the present study was to determine the anti-inflammatory effect of IFN-τ on endometritis using a mouse model of S. aureus-induced endometritis and to elucidate the mechanism of action underlying these effects. In the present study, the effect of IFN-τ on S. aureus growth was monitored by turbidimeter at 600 nm. IFN-τ did not affect S. aureus growth. The histopathological changes indicated that IFN-τ had a protective effect on uterus tissues with S. aureus infection. The ELISA and qPCR results showed the production of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 was decreased with IFN-τ treatment. In contrast, the level of the anti-inflammatory cytokine IL-10 was increased. We further studied the signaling pathway associated with these observations, and the qPCR results showed that the expression of TLR2 was repressed by IFN-τ. Furthermore, the western blotting results showed the phosphorylation of IκB, NF-κB p65, and MAPKs (p38, JNK, and ERK) was inhibited by IFN-τ treatment. The results suggested that IFN-τ may be a potential drug for the treatment of uterine infection due to S. aureus or other infectious inflammatory diseases