LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis.

BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe-/-PSMB8-AS1KI) and global Apoe and proteasome subunit-ß type-9 (Psmb9) double knockout mice (Apoe-/-Psmb9-/-). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe-/-PSMB8-AS1KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe-/- mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe-/-PSMB8-AS1KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-ß type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe-/- mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.

Mechanism of TCF21 Downregulation Leading to Immunosuppression of Tumor-Associated Macrophages in Non-Small Cell Lung Cancer.

Lung cancer, as one of the high-mortality cancers, seriously affects the normal life of people. Non-small cell lung cancer (NSCLC) accounts for a high proportion of the overall incidence of lung cancer, and identifying therapeutic targets of NSCLC is of vital significance. This study attempted to elucidate the regulatory mechanism of transcription factor 21 (TCF21) on the immunosuppressive effect of tumor-associated macrophages (TAM) in NSCLC. The experimental results revealed that the expression of TCF21 was decreased in lung cancer cells and TAM. Macrophage polarization affected T cell viability and tumor-killing greatly, and M2-type polarization reduced the viability and tumor-killing of CD8+T cells. Meanwhile, overexpression of TCF21 promoted the polarization of TAM to M1 macrophages and the enhancement of macrophages to the viability of T cells. Furthermore, there appears to be a targeting relationship between TCF21 and Notch, suggesting that TCF21 exerts its influence via the Notch signaling pathway. This study demonstrated the polarization regulation of TAM to regulate the immunosuppressive effect, which provides novel targets for the treatment of lung cancer.

Multivariate analysis of medical adhesive-related skin injury at the site of peripherally inserted central catheter insertion in cancer patients: A prospective cohort study.

OBJECTIVE: At the site of peripherally inserted central catheter (PICC) catheterization in tumor patients, medical adhesive-related skin injury (MARSI) was reported related to patient age, infusion of certain chemotherapeutic agents, and tumor type, but did not review its relation to the use of clear patches and the puncture site of PICC. This study aims to analyze the risk factors for MARSI in more detail to provide supported data for reducing MARSI. METHOD: Total 382 cancer patients receiving catheterization via PICC were involved in this study from March 1, 2021, to September 28, 2021. According to MARSI occurrence or not, they were assigned into MARSI or non-MARSI group. Univariate and multivariate logistic regressions were used to analyze the risks of MARSI occurrence at PICC insertion site. RESULTS: 15% (60 of 382 cases) resulted in MARSI, out of which 8.1% (31/382) was categorized as contact dermatitis, and 7.1% (27/382) as mechanical injuries. The univariate analysis showed that there were significant differences in six aspects of the study, including BMI, MARSI history, dressing types, treatment by paclitaxel or 5-FU versus oxaliplatin, dressing frequency, and catheterization at biceps brachii medial (p < 0.05). Via multivariate logistic regression analysis, it was discovered that except for previously reported risk factors, dressing change frequency (OR (95% CI) = 7.49 (2.36-23.80), p = 0.001), catheterization at biceps brachii medial (OR (95% CI) = 4.07 (1.82-9.10), p = 0.001), and breast cancer (OR (95% CI) = 3.27 (1.05-10.15), p = 0.041), there were significant risk factors for MARSI occurrence in tumor patients with PICC catheterization. CONCLUSION: Our study revealed a high incidence of MARSI at the PICC insertion site of cancer patients, presenting with contact dermatitis and mechanical injury. Independent risk factors were previous history of MARSI, a diagnosis of breast cancer, frequent dressing replacement, use of paclitaxel or 5-FU, and PICC catheterization at biceps brachii medial.

A novel role for YPEL2 in mediating endothelial cellular senescence via the p53/p21 pathway.

Yippee-like 2 (YPEL2) is expressed in tissues and organs enriched in vascular networks, such as heart, kidney, and lung. However, the roles of YPEL2 in endothelial cell senescence and the expression of YPEL2 in atherosclerotic plaques have not yet been investigated. Here, we report the essential role of YPEL2 in promoting senescence in human umbilical vein endothelial cells (HUVECs) and the upregulation of YPEL2 in human atherosclerotic plaques. YPEL2 was significantly upregulated in both H2O2-induced senescent HUVECs and the arteries of aged mice. Endothelial YPEL2 deficiency significantly decreased H2O2-increased senescence-associated beta-galactosidase (SA-ß-gal) activity and reversed H2O2-inhibited cell viability. Additionally, endothelial YPEL2 knockdown reduced H2O2-promoted THP-1 cell adhesion to HUVECs and downregulated ICAM1 and VCAM1 expression. Mechanistic studies divulged that the p53/p21 pathway was involved in YPEL2-induced cellular senescence. We conclude that YPEL2 promotes cellular senescence via the p53/p21 pathway and that YPEL2 expression is elevated in atherosclerosis. These findings reveal YPEL2 as a potential therapeutic target in aging-associated diseases.

Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway.

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury. However, its effect on spinal cord injury in aged mice remains unclear. Considering the essential role of angiogenesis during the regeneration process, we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells, thereby promoting microvascular regeneration in aged mice after spinal cord injury. In this study, we established young and aged mouse models of contusive spinal cord injury using a modified Allen method. We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord. Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro. Furthermore, intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord, thereby improving neurological function. The role of metformin was reversed by compound C, an adenosine monophosphate-activated protein kinase inhibitor, both in vivo and in vitro, suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury. These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway, thereby improving the neurological function of aged mice after spinal cord injury.

Reproductive outcomes after uterine septum resection in patients with recurrent miscarriage or infertility: a retrospective study in Chinese women.

OBJECTIVE: Septate uterus is the most common structural uterine anomaly, which is related to the adverse pregnancy outcomes in women of childbearing age. This article provides a retrospective review of hysteroscopic uterine septum resection performed in our hospital during recent years, focusing on the patients with recurrent miscarriage and primary infertility, and also to identify which patients are more likely to benefit from the surgery. METHODS: This is a single-center retrospective study. Cases of women who underwent hysteroscopic septum resection at West China Second Hospital of Sichuan University from January 2014 to December 2019, retrieved through the medical record system, were divided into three groups: Group A was the recurrent miscarriage group, Group B had a history of pregnancy with spontaneous abortion once at most, and Group C was the primary infertility group. Each patient was followed up by telephone about further pregnancy, miscarriage and live birth for at least 1 year. RESULTS: A total of 176 surgical patients were included in this study. Group A, B, and C include 42, 74, and 60 cases, respectively. The postoperative pregnancy rates of the three groups were 71.4, 82.4, and 75.0%; live births rates were 50.0, 74.3, and 71.7%; and spontaneous abortion rates were 21.4, 17.6, and 13.3%. 62 patients had a complete uterine septum and 114 had a partial uterine septum. For patients with complete septate uterus, the preoperative pregnancy rate was 54.84% and the pregnancy rate increased to 85.48% after surgery; and yet the preoperative and postoperative pregnancy rates in patients with partial septate uterus were close (from 71.9 to 72.8%). CONCLUSIONS: After uterine septum resection, the pregnancy rate and spontaneous abortion rate in RSA patients were not significantly different from the other two groups, but the live birth rate was still significantly lower. Patients with complete uterine septum may benefit more from surgery. The surgical indications should be carefully and strictly evaluated.

EPSTI1 promotes monocyte adhesion to endothelial cells in vitro via upregulating VCAM-1 and ICAM-1 expression.

Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.

Knockdown of Long Noncoding RNA 01124 Inhibits the Malignant Behaviors of Colon Cancer Cells via miR-654-5p/HAX-1.

Background: Previous studies have shown that long noncoding RNAs (lncRNAs) play a key role in cancer, including colon cancer (CC). However, the exact role of long noncoding RNA 01124 (LINC01124) in CC and its mechanisms of action remain unknown. In this study, we investigated the functional effects and the possible mechanism of LINC01124 in CC. Methods: We first determined the expression of LINC01124 in CC tissues (The Cancer Genome Atlas (TCGA) database) and cell lines (quantitative real-time polymerase chain reaction (qRT-PCR)). Functional analysis via Cell Counting Kit-8 (CCK-8), colony formation, cell cycle, wound healing and Transwell assays were performed, and a mechanistic experiment was performed with the western blotting. The function of LINC01124 was also determined in vivo using nude BALB/c mice. Results: The results showed that LINC01124 was upregulated in CC tissues and cell lines. Functional studies showed that knockdown of LINC01124 significantly suppressed the proliferation, migration, and invasion of colon cancer cells in vitro and in vivo. Subsequent mechanistic experiments indicated that LINC01124 acted as a sponge to suppress microRNA 654-5p, which targeted HAX-1. Downregulation of LINC01124 decreased the expression of HAX-1, and overexpression of the miR-654-5p inhibitor attenuated the sh-LINC01124-induced inhibition of CC cell proliferation, migration, and invasion. Conclusion: Collectively, this study revealed that the knockdown of LINC01124 inhibited the malignant behaviors of CC via the miR-654-5p/HAX-1 axis, suggesting that LINC01124 might be a therapeutic target for CC treatment.

Genus Picrasma: A comprehensive review on its ethnopharmacology, phytochemistry and bioactivities.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Picrasma belongs to the Simaroubaceae family and contains six species which are mainly distributed in tropical and subtropical regions of Asia and America. The barks, roots, stems, branches, or leaves of several Picrasma species have been applied as folk medicines to treat fever, sore throat, dysentery, eczema, nausea, loss of appetite, diabetes mellitus, cancer, and hypertension. AIM OF THE STUDY: A systematic summary on the botanic characterization, ethnopharmacological uses, phytochemistry, bioactivities and toxicity of species belonging to Picrasma was presented to facilitate the exploitation of the therapeutic potential of these plants. MATERIALS AND METHODS: The literatures about Picrasma were retrieved from a series of scientific search engines including Web of Science, SciFinder, PubMed, CNKI, Google Scholar, Elsevier, Wiley, ACS publications, and SpringerLink between 1970 and 2020. Plant names were validated by "The Plant List" (www.theplantlist.org). RESULTS: As ethnopharmacological uses, Picrasma species are valuable folk medicines to treat fever, inflammation, dysentery, eczema, cancer, diabetics, skin infection, and so on. Up to now, a total of 361 compounds including 126 alkaloids, 132 quassinoids, 67 triterpenoids, and 36 miscellaneous compounds were reported from Picrasma species. Quassinoids and alkaloids are the principal constituents in the genus. The extracts and phytochemical constituents of Picrasma species demonstrate a wide range of bioactivities including cytotoxic, anti-inflammatory, antimicrobial, and other activities. CONCLUSIONS: Picrasma species are widely used as traditional medicines, have diverse chemical constituents with obvious biological activities. Nevertheless, further studies are required on the Picrasma species to assert the ethnopharmacological uses, clarify their bioactive constituents, determine pharmacological actions, and toxicity. Therefore, the present review may provide a critical clue for future studies and further exploitations on Picrasma species.

ETHYLENE RESPONSE FACTOR 74 (ERF74) plays an essential role in controlling a respiratory burst oxidase homolog D (RbohD)-dependent mechanism in response to different stresses in Arabidopsis.

Recent studies indicate that the ETHYLENE RESPONSE FACTOR VII (ERF-VII) transcription factor is an important regulator of osmotic and hypoxic stress responses in plants. However, the molecular mechanism of ERF-VII-mediated transcriptional regulation remains unclear. Here, we investigated the role of ERF74 (a member of the ERF-VII protein family) by examining the abiotic stress tolerance of an ERF74 overexpression line and a T-DNA insertion mutant using flow cytometry, transactivation and electrophoretic mobility shift assays. 35S::ERF74 showed enhanced tolerance to drought, high light, heat and aluminum stresses, whereas the T-DNA insertion mutant erf74 and the erf74;erf75 double mutant displayed higher sensitivity. Using flow cytometry analysis, we found that erf74 and erf74;erf75 lines lack the reactive oxygen species (ROS) burst in the early stages of various stresses, as a result of the lower expression level of RESPIRATORY BURST OXIDASE HOMOLOG D (RbohD). Furthermore, ERF74 directly binds to the promoter of RbohD and activates its expression under different abiotic stresses. Moreover, induction of stress marker genes and ROS-scavenging enzyme genes under various stress conditions is dependent on the ERF74-RbohD-ROS signal pathway. We propose a pathway that involves ERF74 acting as an on-off switch controlling an RbohD-dependent mechanism in response to different stresses, subsequently maintaining hydrogen peroxide (H2 O2 ) homeostasis in Arabidopsis.

[Litter decomposition and soil faunal diversity of two understory plant debris in the alpine timberline ecotone of western Sichuan in a snow cover season].

In order to understand the relationship between litter decomposition and soil fauna diversity during snow cover season, litterbags with plant debris of Actinothuidium hookeri, Cystopteris montana, two representative understory plants in the alpine timberline ecotone, and their mixed litter were incubated in the dark coniferous forest, timberline and alpine meadow, respectively. After a snow cover season, the mass loss and soil fauna in litterbags were investigated. After decomposition with a snow cover season, alpine meadow showed the highest mass loss of plant debris in comparison with coniferous forest and timberline, and the mass loss of A. hookeri was more significant. The mixture of two plants debris accelerated the mass loss, especially in the timberline. A total of 968 soil invertebrates, which belonged to 5 classes, 10 orders and 35 families, were captured in litterbags. Acarina and Collembola were the dominant groups in plant debris. The numbers of individuals and groups of soil faunal communities in litter of timberline were higher than those of alpine meadow and dark coniferous forest. Canonical correspondence analysis (CCA) indicated that the groups of soil animals were related closely with the average temperature, and endemic species such as Isoptera and Geophilomorpha were observed only in coniferous forest, while Hemiptera and Psocoptera only in.the alpine meadow. The diversity of soil faunal community was more affected by plant debris varieties in the timberline than in the coniferous forest and alpine meadow. Multiple regression analysis indicated that the average temperature and snow depth explained 30.8% of the variation of litter mass loss rate, soil animals explained 8.3%, and altogether explained 34.1%. Snow was one of the most critical factors impacting the decomposition of A. hookeri and C. montana debris in the alpine timberline ecotone.

[Litter decomposition and lignocellulose enzyme activities of Actinothuidium hookeri and Cys- topteris montana in alpine timberline ecotone of western Sichuan, China].

The mass loss and lignocellulose enzyme activities of Actinothuidium hookeri residues and Cystopteris montana leaf litter in coniferous forest and timberline of western Sichuan, China were investigated. The results showed that both the mass loss rates of A. hookeri and C. Montana in timberline were higher than those in coniferous forest, while enzyme activities in timberline were lower than those in coniferous forest which was contrast with the hypothesis. The mass loss of two ground covers had significant differences in different seasons. The mass loss rate of A. hookeri in snow-covered season accounted for 69.8% and 83.0% of the whole year' s in timberline and coniferous forest, while that of C. montana in the growing season accounted for 82.6% and 83.4% of the whole year' s in timberline and coniferous forest, respectively. C. montana leaf litter decayed faster in the growing season, which was consistent with its higher cellulase activity in the growing season. The result illustrated that the enzymatic hydrolysis of cellulose and hemicellulose might be the main driving force for the early stage of litter decomposition. Multiple linear regression analysis showed that environmental factors and initial litter quality could explain 45.8%-85.1% variation of enzyme activity. The enzyme activities of A. hookeri and C. montana in the process of decomposition were mainly affected by the freeze-thaw cycle in snow-covered season.

Formation of N-heterocyclic diphosphine ligands from Ag(I)-assisted condensation reactions between bdppeda and formaldehyde and their binuclear silver(I) complexes.

The reaction of [Ag(MeCN)(4)]ClO(4) with N,N,N',N'-tetra(diphenylphosphanylmethyl)ethylenediamine (dppeda) in CH(2)Cl(2)/MeOH afforded an unexpected cationic binuclear complex [Ag(2)(L(1))(2)(η,η-µ-ClO(4))(2)](ClO(4))(2) (L(1) = N,N'-bis(diphenylphosphanylmethyl)-3H-4,5-dihydroimidazole-1-ium) (1). Compound 1 was also prepared in high yield from reactions of [Ag(MeCN)(4)]ClO(4) with N,N'-bis(diphenylphosphanylmethyl)ethylenediamine (bdppeda) in the presence of formaldehyde (HCHO) or formic acid (HCOOH). Analogous reactions of AgCl with bdppeda and HCHO resulted in the formation a neutral binuclear complex [Ag(2)(L(2))(2)(µ-Cl)(2)] (L(2) = N,N-bis(diphenylphosphanylmethyl)-tetrahydroimidazole) (2). Treatment of 1 with concentrated HCl gave rise to a partially anion-exchanged product [Ag(2)(L(1))(2)(µ-Cl)(2)](ClO(4))(2) (3). Compounds 1 and 3 have a similar cationic binuclear structure, in which a [Ag(2)(η,η-µ-ClO(4))(2)] or [Ag(2)(µ-Cl)(2)] ring is sandwiched by two in situ-formed cationic L(1) ligands. The L(1) ligand may be generated by the Ag(I)-assisted condensation reaction between bdppeda and HCHO or HCOOH. Compound 2 holds a neutral binuclear structure, in which a [Ag(2)(µ-Cl)(2)] ring is connected by two in situ-formed L(2) ligands from its top and bottom sites. The neutral ligand L(2) may be produced from another Ag(I)-assisted condensation reaction between bdppeda and HCHO. The in situ formation of the L(1) and L(2) ligands provides a new route to the N-heterocyclic diphosphine ligands, and an interesting insight into the coordination chemistry of their metal complexes.