Puerarin Induces Ferroptosis in Colorectal Cancer Cells via Triggering NCOA4 Upregulation.

Puerarin shows promise as an anti-cancer compound, but its mechanism of action remains unclear. Here we explored whether and how it promotes ferroptosis in a colorectal cancer cell line. The level of ferroptosis and expression of autophagy proteins were compared between puerarin-treated HT-29 cells expressing normal or reduced levels of the autophagy protein ATG5 or the ferritinophagy protein nuclear receptor coactivator 4 (NCOA4). Puerarin increased lipid peroxidation and inhibited cell proliferation in a dose-dependent manner, indicating the induction of ferroptosis. These effects were partially reversed by ferrostatin-1, a scavenger of reactive oxygen species; by the iron chelator deferiprone; by repression of autophagy through administration of 3-methyladenine or knockdown of autophagy-related gene 5 (ATG5); or by repression of ferritinophagy through NCOA4 knockdown. Puerarin may induce the proliferative inhibition of colorectal cancer cells by triggering ferroptosis through a mechanism requiring NCOA4 ferritinophagy.

The risk of intrauterine exposure to SARS-CoV-2 in female COVID-19 patients: A comprehensive review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that has caused fatal infectious diseases and global spread. This novel coronavirus attacks target cells through the interaction of spike protein and angiotensin-converting enzyme II (ACE2), leading to different clinical symptoms. However, for a successful pregnancy, a well-established in-uterine environment includes a specific immune environment, and multi-interactions between specific cell types are prerequisites. The immune-related changes in patients infected with novel coronavirus could interfere with the immune microenvironment in the uterus, leading to fetal loss. We first reviewed the intrauterine environment in the normal development process and the possible pregnancy outcome in the infection state. Then, we summarized the immune response induced by SARS-CoV-2 in patients and analyzed the changes in ACE2 expression in the female reproductive system. Finally, the present observational evidence of infection in pregnant women was also reviewed.

Dissection of the Pearl of Csaba pedigree identifies key genomic segments related to early ripening in grape.

Pearl of Csaba (PC) is a valuable backbone parent for early-ripening grapevine (Vitis vinifera) breeding, from which many excellent early ripening varieties have been bred. However, the genetic basis of the stable inheritance of its early ripening trait remains largely unknown. Here, the pedigree, consisting of 40 varieties derived from PC, was re-sequenced for an average depth of ∼30×. Combined with the resequencing data of 24 other late-ripening varieties, 5,795,881 high-quality single nucleotide polymorphisms (SNPs) were identified following a strict filtering pipeline. The population genetic analysis showed that these varieties could be distinguished clearly, and the pedigree was characterized by lower nucleotide diversity and stronger linkage disequilibrium than the non-pedigree varieties. The conserved haplotypes (CHs) transmitted in the pedigree were obtained via identity-by-descent analysis. Subsequently, the key genomic segments were identified based on the combination analysis of haplotypes, selective signatures, known ripening-related quantitative trait loci (QTLs), and transcriptomic data. The results demonstrated that varieties with a superior haplotype, H1, significantly (one-way ANOVA, P < 0.001) exhibited early grapevine berry development. Further analyses indicated that H1 encompassed VIT_16s0039g00720 encoding a folate/biopterin transporter protein (VvFBT) with a missense mutation. VvFBT was specifically and highly expressed during grapevine berry development, particularly at veraison. Exogenous folate treatment advanced the veraison of "Kyoho". This work uncovered core haplotypes and genomic segments related to the early ripening trait of PC and provided an important reference for the molecular breeding of early-ripening grapevine varieties.

The role of NMDA receptors in rat propofol self-administration.

BACKGROUND: Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators neural plasticity, neuronal development, addiction, and neurodegeneration. In the present study, we explored the role of these receptors in the context of rat propofol self-administration. METHODS: Sprague-Dawley Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using a fixed-ratio (FR) schedule over the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, followed 10 min later by a propofol self-administration session. RESULTS: After training, rats successfully underwent acquisition of propofol self-administration, as evidenced by a significant and stable rise in the number of active nose-pokes resulting in propofol administration relative to the number of control inactive nose-pokes (P < 0.01). As compared to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited a significantly greater number of propofol infusions (F (3, 28) = 4.372, P < 0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg of this compound. In addition, MK-801 failed to alter the numbers of active (F (3, 28) = 1.353, P > 0.05) or inactive (F (3, 28) = 0.047, P > 0.05) responses in these study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg MK-801 (P = 0.006, P < 0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group displayed a significant reduction in the number of active nose-poke responses (F (3, 20) = 20.8673, P < 0.01) and the number of sucrose pellets (F (3, 20) = 23.77, P < 0.01), while their locomotor activity was increased (F (3, 20) = 22.812, P < 0.01). CONCLUSION: These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

[Research advances in the function of T cells at the maternal-fetal interface].

Immune tolerance at maternal-fetal interface is the basis for establishment and maintenance of successful pregnancy. T cells are pivotal compositions of uterine decidual immune cells, which are required to mediate anti-infection immunity and protect embryos from external antigens attack. T cells also participate in the complex immune regulation process of maternal acceptance of semi-allogeneic embryos, and play an important role in regulating embryo implantation and maintaining pregnancy. Its dysfunction may lead to early pregnancy failures or mid-late pregnancy complications. This review summarizes the compositions, phenotypic characteristics and functions of decidual T cells at the maternal-fetal interface in recent years, and further describes the regulation of decidual CD4+ and CD8+ T cells in maternal-fetal immune tolerance as well as the molecular mechanisms of abnormal regulation leading to early pregnancy failures. Through the in-depth understanding the mechanism of maternal-fetal immune regulation, it supplies a novel concept on maternal-fetal immune tolerance and new clues for the immunotherapy of pregnancy-related diseases.

microRNA-186 inhibition of PI3K-AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis.

Chondrocyte apoptosis has been implicated as a major pathological osteoarthritis (OA) change in humans and experimental animals. We evaluate the ability of miR-186 on chondrocyte apoptosis and proliferation in OA and elucidate the underlying mechanism concerning the regulation of miR-186 in OA. Gene expression microarray analysis was performed to screen differentially expressed messenger RNAs (mRNAs) in OA. To validate the effect of miR-186 on chondrocyte apoptosis, we upregulated or downregulated endogenous miR-186 using mimics or inhibitors. Next, to better understand the regulatory mechanism for miR-186 governing SPP1, we suppressed the endogenous expression of SPP1 by small interfering RNA (siRNA) against SPP1 in chondrocytes. We identified SPP1 is highly expressed in OA according to an mRNA microarray data set GSE82107. After intra-articular injection of papain into mice, the miR-186 is downregulated while the SPP1 is reciprocal, with dysregulated PI3K-AKT pathway in OA cartilages. Intriguingly, miR-186 was shown to increase chondrocyte survival, facilitate cell cycle entry in OA chondrocytes, and inhibit chondrocyte apoptosis in vitro by modulation of pro- and antiapoptotic factors. The determination of luciferase activity suggested that miR-186 negatively targets SPP1. Furthermore, we found that the effect of miR-186 suppression on OA chondrocytes was lost when SPP1 was suppressed by siRNA, suggesting that miR-186 affected chondrocytes by targeting and depleting SPP1, a regulator of PI3K-AKT pathway. Our findings reveal a novel mechanism by which miR-186 inhibits chondrocyte apoptosis in OA by interacting with SPP1 and regulating PI3K-AKT pathway. Restoring miR-186 might be a future therapeutic strategy for OA.

Effects of miR-338 on morphine tolerance by targeting CXCR4 in a rat model of bone cancer pain.

The present study aimed to investigate the effects of miR-338 on morphine tolerance through the targeting of CXC chemokine receptor-4 (CXCR4) in a rat model of bone cancer pain (BCP). Sprague-Dawley (SD) rats were obtained and divided into model saline (n=10), model morphine (n=50), normal saline (n=10) and normal morphine (healthy rats, n=10) groups. After BCP rat model establishment, the remaining SD rats (n=40) in the model saline group were assigned into pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA, blank and PBS groups. Luciferase reporter gene assay was used for luciferase activity. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to detect the miR-338 and CXCR4 mRNA and protein expression. The model saline group showed increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group, and the model morphine group had increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group. The mRNA and protein expressions of miR-338 in the pLV-THM-miR-338 group increased remarkably while those of the pLV-THM-anti-miR-338 group decreased significantly compared with the CXCR4 shRNA, blank and PBS groups. The pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA and CXCR4 mRNA groups all had lower mRNA and protein expressions of CXCR4 than those in the blank and PBS groups. miR-338 exerts significant influence in the inhibition of morphine tolerance by suppressing CXCR4 in BCP.

[FISH analysis of meiotic segregation results of the spermatozoa from male pericentric inversion carriers].

OBJECTIVE: To analyze the meiotic segregation results of the spermatozoa from male pericentric inversion carriers by fluorescence in-situ hybridization (FISH). METHODS: Using chemical depolymerization and multicolor FISH, we analyzed the meiotic segregation results of the spermatozoa from 4 male pericentric inversion carriers. RESULTS: Of the 4 males studied, 46,XY,inv(9) (p11q12) was found in 2, 46,XY,inv(9) (p11q13) in 1 and 46,XY,inv(6) (p22q24) in the other; the lengths of the inverted segments represented 16.0, 16.0, 21.0 and 76.0% of the size of the whole chromosome involved; and the frequencies of recombinant sperm were 0.2, 0.4, 0.3 and 43.9%, del(p)/dup(q) accounting for 22.4% and del(q)/dup(p) 21.5%, respectively. CONCLUSION: Males with pericentric inversion may produce spermatozoa with recombinant chromosomes and the rate of recombination varies principally according to the size proportion to the whole chromosome involved. The results of FISH analysis of chromosomal unbalanced spermatozoa can provide accurate personalized information on the genetic risk of fertility.

[Effect of the new propofol target controlled infusion system in children undergoing high ligation of hernial sac].

OBJECTIVE: To discuss the effect of the new target controlled infusion (TCI) system in Chinese children undergoing minor operation and compared with TCI system with Marsh parameters. METHODS: Ninety ASA I, aged 3 - 5 yrs children undergoing elective unilateral high ligation of hernial sac under general anesthesia were randomly divided into group L (n = 45) and group M (n = 45) 2 groups. All subjects were unpremedicated. Systolic blood pressure (SBP), diastolic blood pressure (DBP), ECG, SpO2 and BIS were monitored. Patients of Group L and group M were anesthetized with propofol by Lian propofol TCI system and Marsh system respectively, combined with regional block. The target plasma concentration of TCI system was set at 6 microg/ml initially and up-regulated 1 microg/ml gradually if obvious body movement occurred while skin incision. If the target plasma concentration up to 8 microg/ml but there still had body movement, the TCI venous anesthesia was replaced by inhaled anesthesia. HR, RR, SBP, DBP and BIS were recorded in time points of baseline (T(0)), after the induction (T(1)), skin incision (T(2)), 3, 5 min after skin incision (T(3), T(4)), the end of operation (T(5)). Complications, the awakening time and the number of cases which anesthetized with different propofol plasma concentrations or inhaled anesthesia were recorded respectively as well. RESULTS: The number of cases which completed the operation under TCI plasma concentration 6 microg/ml in group L were significantly more than those in group M (P < 0.01). There were significantly different of T(1)-T(4) values of HR, RR, SBP, DBP and BIS in group M (P < 0.05), but not in group L. Compared with group L, T(2)-T(4) values of HR, RR, SBP, DBP and BIS were higher in group M (P < 0.05 or 0.01). Complications were lower in group L than those in group M. CONCLUSION: Compared with Marsh system, propofol 6 microg/ml plasma concentration with the new target controlled infusion system applied in Chinese children undergoing unilateral high ligation of hernial sac could maintain stable hemodynamics, less stress reaction and complications.