Loss of Endothelial Annexin A1 Aggravates Inflammation-Induched Vascular Aging.

Chronic inflammation is increasingly considered as the most important component of vascular aging, contributing to the progression of age-related cardiovascular diseases. To delay the process of vascular aging, anti-inflammation may be an effective measure. The anti-inflammatory factor annexin A1 (ANXA1) is shown to participate in several age-related diseases; however, its function during vascular aging remains unclear. Here, an ANXA1 knockout (ANXA1-/-) and an endothelial cell-specific ANXA1 deletion mouse (ANXA1△EC) model are used to investigate the role of ANXA1 in vascular aging. ANXA1 depletion exacerbates vascular remodeling and dysfunction while upregulates age- and inflammation-related protein expression. Conversely, Ac2-26 (a mimetic peptide of ANXA1) supplementation reverses this phenomenon. Furthermore, long-term tumor necrosis factor-alpha (TNF-α) induction of human umbilical vein endothelial cells (HUVECs) increases cell senescence. Finally, the senescence-associated secretory phenotype and senescence-related protein expression, rates of senescence-ß-galactosidase positivity, cell cycle arrest, cell migration, and tube formation ability are observed in both ANXA1-knockdown HUVECs and overexpressed ANXA1-TNF-α induced senescent HUVECs. They also explore the impact of formyl peptide receptor 2 (a receptor of ANXA1) in an ANXA1 overexpression inflammatory model. These data provide compelling evidence that age-related inflammation in arteries contributes to senescent endothelial cells that promote vascular aging.

16S rRNA gene sequencing reveals the correlation between the gut microbiota and the susceptibility to pathological scars.

The gut microbiome profile in patients with pathological scars remains rarely known, especially those patients who are susceptible to pathological scars. Previous studies demonstrated that gut microbial dysbiosis can promote the development of a series of diseases via the interaction between gut microbiota and host. The current study aimed to explore the gut microbiota of patients who are prone to suffer from pathological scars. 35 patients with pathological scars (PS group) and 40 patients with normal scars (NS group) were recruited for collection of fecal samples to sequence the 16S ribosomal RNA (16S rRNA) V3-V4 region of gut microbiota. Alpha diversity of gut microbiota showed a significant difference between NS group and PS group, and beta diversity indicated that the composition of gut microbiota in NS and PS participants was different, which implied that dysbiosis exhibits in patients who are susceptible to pathological scars. Based on phylum, genus, species levels, we demonstrated that the changing in some gut microbiota (Firmicutes; Bacteroides; Escherichia coli, etc.) may contribute to the occurrence or development of pathological scars. Moreover, the interaction network of gut microbiota in NS and PS group clearly revealed the different interaction model of each group. Our study has preliminary confirmed that dysbiosis exhibits in patients who are susceptible to pathological scars, and provide a new insight regarding the role of the gut microbiome in PS development and progression.

Prevalence of Mycoplasma pneumoniae among children undergoing physical examination / 中华微生物学和免疫学杂志

Objective:To investigate the prevalence of Mycoplasma pneumoniae ( Mp) in children undergoing physical examination. Methods:This study randomly enrolled 1 303 children at the age of 6-12 years who underwent physical examination in 2023. Their oral and pharyngeal swabs as well as venous blood samples were collected. The prevalence of Mp in these subjects was detected using isolation and culturing, nucleic acid detection and serological test. Chi-square test was used for statistical analysis. Results:Among the 1 303 children, the detection rate of Mp was 4.1% (53/1 303) by culturing, 7.3% (95/1 303) by nucleic acid detection and 13.6% (177/1 303) by serological test. Statistical analysis showed that there were significant differences in the the detection rates of Mp among children undergoing physical examination between the three methods ( P<0.05). Conclusions:The detection rate of Mp in children undergoing physical examination in 2023 was about 4.1%. Isolation and culturing was more accurate than nucleic acid detection and serological test in the detection of Mp in healthy population as the latter two methods would overestimate the rate.

Asiaticoside reverses M2 phenotype macrophage polarization-evoked osteosarcoma cell malignant behaviour by TRAF6/NF-κB inhibition.

CONTEXT: M2 phenotype macrophage polarization is an attractive target for therapeutic intervention. Asiaticoside (ATS) has multiple pharmacological functions. OBJECTIVE: This study investigates the effect of ATS on M2 phenotype macrophage polarization in osteosarcoma. MATERIALS AND METHODS: The differentiation of human THP-1 monocytes into M0 phenotype macrophages was induced by 100 nM phorbol myristate acetate for 24 h, and treated with 20 ng/mL IL-4 and 20 ng/mL IL-13 for 48 h to obtain M2 phenotype macrophages. The function of ATS on the growth and invasion was investigated by cell counting kit-8, transwell, and western blot under the co-culture of M2 phenotype macrophages and osteosarcoma cells for 24 h. The mechanism of ATS on osteosarcoma was assessed using molecular experiments. RESULTS: ATS reduced the THP-1 cell viability with an IC50 of 128.67 µM. Also, ATS repressed the M2 phenotype macrophage polarization induced by IL-4/IL-13, and the effect was most notably at a 40 µM dose. ATS (40 µM) restrained the growth and invasion of osteosarcoma cells induced by M2 phenotype macrophages. In addition, ATS reduced the tumour necrosis factor receptor-associated factor 6 (TRAF6)/NF-κB activity in osteosarcoma cells and the TRAF6 knockdown reduced the growth and invasion of osteosarcoma cells induced by M2 phenotype macrophages. TRAF6 (2 µg/mL) attenuated the inhibitory effect of ATS on the growth and invasion of osteosarcoma cells caused by M2 phenotype macrophages. In vivo studies further confirmed ATS (2.5, 5, or 10 mg/kg) repressed osteosarcoma tumour growth. DISCUSSION AND CONCLUSIONS: ATS reversed M2 phenotype macrophage polarization-evoked osteosarcoma cell malignant behaviour by reducing TRAF6/NF-κB activity, suggesting ATS might be a promising drug for the clinical treatment of osteosarcoma.

PAX5 Haploinsufficiency Induces Low T Cell Infiltration in the Cancer Microenvironment via Reduced Chemokines.

AIM: To investigate the effects of PAXT mutations on tumor immunity. BACKGROUND: Loss of function of PAX5 plays a key role in the PAX5 mutation tumor. OBJECTIVE: PAX5 haploinsufficiency promoting tumorigenesis is related to immune escape, but there was no report about mechanisms of PAX5 mutation inducing tumor immunological escape. METHODS: We constructed the PAX5 haplodeletion A20 cell lines using gene-editing technology, built allografted A20 tumor models and evaluated the effect of PAX5 haplodeletion on T cells and chemokines in the tumor microenvironment (TME). RESULTS: Our results from different methods indicated percentages of CD3+ CD4+ T cells and CD3+ CD8+ T cells in TME of PAX5 haplodeletion clones decreased significantly compared with that of PAX5 wild type control. Several chemokines, such as Ccl2, Ccl4, Cxcl9 and Cxcl10, in TME of PAX5. CONCLUSION: Our study showed that PAX5 haploinsufficiency induced low T cell infiltration in TME using decreased chemokines.

Single-Cell RNA Sequencing and Assay for Transposase-Accessible Chromatin Using Sequencing Reveals Cellular and Molecular Dynamics of Aortic Aging in Mice.

OBJECTIVE: The impact of vascular aging on cardiovascular diseases has been extensively studied; however, little is known regarding the cellular and molecular mechanisms underlying age-related vascular aging in aortic cellular subpopulations. Approach and Results: Transcriptomes and transposase-accessible chromatin profiles from the aortas of 4-, 26-, and 86-week-old C57/BL6J mice were analyzed using single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. By integrating the heterogeneous transcriptome and chromatin accessibility data, we identified cell-specific TF (transcription factor) regulatory networks and open chromatin states. We also determined that aortic aging affects cell interactions, inflammation, cell type composition, dysregulation of transcriptional control, and chromatin accessibility. Endothelial cells 1 have higher gene set activity related to cellular senescence and aging than do endothelial cells 2. Moreover, construction of senescence trajectories shows that endothelial cell 1 and fibroblast senescence is associated with distinct TF open chromatin states and an mRNA expression model. CONCLUSIONS: Our data provide a system-wide model for transcriptional and epigenetic regulation during aortic aging at single-cell resolution.

Mechanism of Traditional Chinese Medicine in Treatment of Autism Spectrum Disorder Based on Heart and Spleen / 中国实验方剂学杂志

Autism spectrum disorder （ASD） is a common neurodevelopmental disorder in childhood， whereas there is no specific medicine at present. There are more and more researches on the treatment of ASD with traditional Chinese medicine（TCM） which the curative effect is reliable. The heart and spleen are the main viscera for the treatment of ASD， but there is still a lack of in-depth analysis of the mechanism of TCM. In order to explore the relationship between the core symptoms of ASD and the heart and spleen， this article specifically explores the theoretical origins of the heart and the spleen in the formation of the core symptoms of ASD， and to clarify the role of the heart and spleen in the occurrence and development of the two core symptoms of ASD from the perspective of TCM. In view of social communication and communication obstacles， the author puts forward and explains the language problems of children with ASD based on the functions of the heart and spleen， the theory of the viscera， the ascription of the meridians， and the classics. The mechanism of the heart and spleen in TCM about the failure of the spleen， the loss of the heart， and the endogenous phlegm. Aiming at the mechanism of the stereotyped symptoms of abnormal behaviors in children with ASD， this paper proposes and explains the TCM mechanism of constant deficiency of the spleen and dereliction of duty， leading to loss of mind， heart and spleen injury， and finally a series of stereotypes and strange syndromes due to lack of spirit. Through the analysis and excavation of TCM theory， it explores theoretical basis for ASD from the theory of heart and spleen， with a view to preliminarily constructing the theoretical framework of TCM syndrome differentiation and treatment of the deficiency of both the heart and spleen， and provide theoretical reference for TCM syndrome differentiation and treatment of ASD. The treatment of ASD from the differentiation of symptoms and signs of the heart and spleen is supported by a strong theoretical basis of TCM， and the rationale， law and prescriptions are complete， which may be the direction of screening effective TCM prescriptions for the treatment of ASD in the future.

Knockdown lncRNA DLEU1 Inhibits Gliomas Progression and Promotes Temozolomide Chemosensitivity by Regulating Autophagy.

Gliomas are the most fatal malignant cerebral tumors. Temozolomide (TMZ), as the primary chemotherapy drug, has been widely used in clinics. However, resistance of TMZ still remains to poor defined. LncRNAs have been reported to play crucial roles in progression of various cancers and resistance of multiple drugs. However, the biological function and underlying mechanisms of most lncRNAs in glioma still remains unclear. Based on the TCGA database, a total of 94 differentially expressed lncRNAs, including 16 up-regulated genes and 78 downregulated genes were identified between gliomas and normal brain tissues. Subsequently, lncRNA DLEU1, HOTAIR, and LOC00132111 were tested to be significantly related to overall survival (OS) between high- and low-expression groups. Additionally, we verified that lncRNA DLEU1 was high expressed in 108 gliomas, compared with 19 normal brain tissues. And high expression of lncRNA DLEU1 predicted a poor prognosis (HR = 1.703, 95%CI: 1.133-2.917, p-value = 0.0159). Moreover, functional assays revealed that knockdown of lncRNA DLEU1 could suppress the proliferation by inducing cell cycle arrest at G1 phase and reducing the S phase by down-regulating the CyclinD1 and p-AKT, as the well as migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) markers, such as ZEB1, N-cadherin, ß-catenin and snail in glioma cells. Furthermore, silencing lncRNA DLEU1 suppressed TMZ-activated autophagy via regulating the expression of P62 and LC3, and promoted sensitivity of glioma cells to TMZ by triggering apoptosis. Conclusively, our study indicated that lncRNA DLEU1 might perform as a prognostic potential target and underlying therapeutic target for sensitivity of glioma to TMZ.

M6A RNA Methylation Regulator HNRNPC Contributes to Tumorigenesis and Predicts Prognosis in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most malignant glioma with a high death rate. N6-methyladenosine (m6A) RNA methylation plays an increasingly important role in tumors. The current study aimed to determine the function of the regulators of m6A RNA methylation in GBM. We evaluated the difference, interaction, and correlation of these regulators with TCGA database. HNRNPC, WTAP, YTHDF2 and, YTHDF1 were significantly upregulated in GBM. To explore the expression characteristics of regulators in GBM, we defined two subgroups through consensus cluster. HNRNPC, WTAP, and YTHDF2 were significantly upregulated in the cluster2 which had a good overall survival (OS). To investigate the prognostic value of regulators, we used lasso cox regression algorithm to screen an independent prognostic risk characteristic based on the expression of HNRNPC, ZC3H13, and YTHDF2. The prognostic feature between the low and high-risk groups was significantly different (P < 0.05), which could predict significance of prognosis (area under the curve (AUC) = 0.819). Moreover, we used western blot, RT-PCR, and immunohistochemical staining to verify the expression of HNRNPC was associated with malignancy and development of gliomas. Similarly, the high expression of HNRNPC had a good prognosis. In conclusion, HNRNPC is a vital participant in the malignant progression of GBM and might be valuable for prognosis.

[Construction and Denitrification Performance of A2/O Based on Partial Nitrification Coupled with an ANAMMOX System].

To resolve the issue of existing municipal wastewater treatment plants (WWTPs) in China with an insufficient influent carbon source, a bench-scale A2/O process based on partial nitrification coupled with ANAMMOX was constructed by controlling aeration partition ratio, dissolved oxygen (DO) concentration, and sludge retention time (SRT). In this study, the nitrogen removal performance, nitrogen removal pathway, and microbial community structure of the system under different conditions were investigated. The results showed that the system had excellent nitrogen removal efficiency at low-C/N influent (C/N=5). The A2/O reactor had experienced the co-culture stage (Phase 1), screening stage (Phase 2-3), and enrichment stage (Phase 4) successively during the 140-day experiment, and the nitrogen removal pathway changed from nitrification and denitrification to partial nitrification coupled ANAMMOX in the end. The optimal removal efficiencies of 97.69% for NH4+-N and 87.83% for TN were obtained in the enrichment stage (Phase 4), and the effluent concentration of NH4+-N and TN were 1.20 mg·L-1 and 7.03 mg·L-1, respectively. Illumina MiSeq sequencing results showed that the enrichment of AOB including Nitrosomonas and Nitrosospira and the elimination of NOB including Nitrospira, Nitrococcus, and Nitrobacter were the main causes of achieving partial nitrification in the system. The enrichment of AnAOB including Candidatus Kuenenia and Candidatus Jettenia was the key point for the occurrence of ANAMMOX in the system, and thus, played an important role in the achievement of advanced nitrogen removal.

Effect of baicalin on growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡ and ERK1/2 / 中国中药杂志

The aim of this study was to observe the effect of baicalin on the growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡand ERK1/2.In the present study,a total of 40 SHR rats were randomly divided into model group,methylphenidate hydrochloride group,and low,medium,and high dose baicalin groups,with 8 rats in each group.Eight WKYrats were selected as a normal control group.The methylphenidate hydrochloride group(0.07 g·L~(-1))and the low(3.33 g·L~(-1)),medium(6.67 g·L~(-1)),and high dose(10 g·L~(-1))baicalin groups received corresponding drugs by gavage administration according to the body weight(0.015 m L·g~(-1)),while the normal group and the model group received the same volume of normal saline by gavage.Thegavage administration lasted for 4 weeks,twice a day.The body weight of the rats and the amount of remaining feed were weighed daily,and the growth state of the rats was statistically evaluated weekly.Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structures.The Ca MKⅡand ERK1/2 protein and mRNA expression levels were detected with Western blot and Real-time PCR methods,respectively.RESULTS: showed that baicalin did not affect the normal eating and weight gain of rats,and the weight gain of rats was even more significant than that in the normal group(P<0.05).In the study of its effects on Ca MKⅡand ERK1/2 protein expression in rat synaptosomes,the expression of both proteins in each drug-administered group was higher than that in the model group(P<0.05);besides,the expression levels of Ca MKⅡand ERK1/2 protein were significantly increased in both baicalin high dose group and the methylphenidate hydrochloride group(P<0.05).The relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosome was detected by PCR.The results showed that medium and high doses of baicalin and methylphenidate hydrochloride significantly increased the relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosomes of SHR rats(P<0.05).In conclusion,baicalin does not affect the normal growth and development of SHR rats,so it is safe for administration.Both baicalin and methylphenidate hydrochloride could up-regulate the relative expression of Ca MKⅡand ERK1/2 in mRNA and protein,and the pharmacodynamic stability of baicalin is in a dose-dependent manner to certain extent.

Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice.

Gut microbiota can influence the aging process and may modulate aging-related changes in cognitive function. Trimethylamine-N-oxide (TMAO), a metabolite of intestinal flora, has been shown to be closely associated with cardiovascular disease and other diseases. However, the relationship between TMAO and aging, especially brain aging, has not been fully elucidated. To explore the relationship between TMAO and brain aging, we analysed the plasma levels of TMAO in both humans and mice and administered exogenous TMAO to 24-week-old senescence-accelerated prone mouse strain 8 (SAMP8) and age-matched senescence-accelerated mouse resistant 1 (SAMR1) mice for 16 weeks. We found that the plasma levels of TMAO increased in both the elderly and the aged mice. Compared with SAMR1-control mice, SAMP8-control mice exhibited a brain aging phenotype characterized by more senescent cells in the hippocampal CA3 region and cognitive dysfunction. Surprisingly, TMAO treatment increased the number of senescent cells, which were primarily neurons, and enhanced the mitochondrial impairments and superoxide production. Moreover, we observed that TMAO treatment increased synaptic damage and reduced the expression levels of synaptic plasticity-related proteins by inhibiting the mTOR signalling pathway, which induces and aggravates aging-related cognitive dysfunction in SAMR1 and SAMP8 mice, respectively. Our findings suggested that TMAO could induce brain aging and age-related cognitive dysfunction in SAMR1 mice and aggravate the cerebral aging process of SAMP8 mice, which might provide new insight into the effects of intestinal microbiota on the brain aging process and help to delay senescence by regulating intestinal flora metabolites.

Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress.

Trimethylamine-N-oxide (TMAO), gut microbiota-dependent metabolites, has been shown to be associated with cardiovascular diseases. However, little is known about the relationship between TMAO and vascular aging. Here, we observed a change in TMAO during the aging process and the effects of TMAO on vascular aging and endothelial cell (EC) senescence. We analyzed age-related plasma levels of TMAO in young adults (18-44 years old), older adults (≥ 65 years old), and 1-month-old, 3-month-old, 6-month-old and 10-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-accelerated mouse resistance 1 (SAMR1) models. We found that circulating TMAO increased with age both in humans and mice. Next, we observed that a TMAO treatment for 16 weeks induced vascular aging in SAMR1 mice and accelerated the process in SAMP8 mice, as measured by an upregulation of senescence markers including senescence-associated ß-galactosidase (SA-ß-gal), p53, and p21, vascular dysfunction and remodeling. In vitro, we demonstrated that prolonged TMAO treatment induced senescence in human umbilical vein endothelial cells (HUVECs), characterized by reduced cell proliferation, increased expressions of senescence markers, stagnate G0/G1, and impaired cell migration. Furthermore, TMAO suppressed sirtuin 1 (SIRT1) expression and increased oxidative stress both in vivo and in vitro and then activated the p53/p21/Rb pathway resulting in increased p53, acetylation of p53, p21, and decreased CDK2, cyclinE1, and phosphorylation of Rb. In summary, these data suggest that elevated circulating TMAO during the aging process may deteriorate EC senescence and vascular aging, which is probably associated with repression of SIRT1 expression and increased oxidative stress, and, thus, the activation of the p53/p21/Rb pathway.

Cilia loss sensitizes cells to transformation by activating the mevalonate pathway.

Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through ß catenin-T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by ß-catenin-TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples. Moreover, disruption of ciliogenesis by depleting Tg737 dramatically promoted tumorigenesis in the PDAC mouse model, driven by KrasG12D , which was inhibited by statin, an inhibitor of the MVA pathway. Collectively, this study emphasizes the crucial roles of cilia in governing the early steps of the transformation by activating the MVA pathway, suggesting that statin has therapeutic potential for pancreatic cancer treatment.

Evidence For Hmgn2 Involvement in Mouse Embryo Implantation and Decidualization.

BACKGROUND/AIMS: Hmgn2 is involved in regulating embryonic development, but its physiological function during embryo implantation and decidualization remains unknown. METHODS: In situ hybridization, real-time PCR, RNA interference, gene overexpression and MTS assay were used to examine the expression of Hmgn2 in mouse uterus during the pre-implantation period and explore its function and regulatory mechanisms in epithelial adhesion junction and stromal cell proliferation and differentiation. RESULTS: Hmgn2 was primarily accumulated in uterine luminal epithelia on day 4 of pregnancy and subluminal stromal cells around the implanting blastocyst at implantation sites on day 5. Similar results were observed during delayed implantation and activation. Meanwhile, Hmgn2 expression was visualized in the decidua. In uterine epithelial cells, silencing of Hmgn2 by specific siRNA reduced the expression of adhesion molecules Cdh1, Cdh2 and Ctnnb1 and enhanced the expression of Muc1, whereas constitutive activation of Hmgn2 exhibited the opposite effects, suggesting a role for Hmgn2 in attachment reaction during embryo implantation. Estrogen stimulated the expression of Hmgn2 in uterine epithelia, but the stimulation was abrogated by ER antagonist ICI 182,780. Further analysis evidenced that attenuation of Hmgn2 might eliminate the regulation of estrogen on the expression of Cdh1, Cdh2 and Ctnnb1. In uterine stromal cells, progesterone induced the accumulation of Hmgn2 which advanced the expression of Prl8a2 and Prl3c1, two well-known differentiation markers for decidualization, but did not affect the proliferation of stromal cells. Knockdown of Hmgn2 blocked the progesterone-induced differentiation of uterine stromal cells. Moreover, Hmgn2 might serve as an intermediate to mediate the regulation of progesterone on Hand2. CONCLUSION: Hmgn2 may play an important role during embryo implantation and decidualization.

Analysis on the Potential Security Risks of the VPN Application under Android Platform / 医学信息学杂志

The paper states the principles and characteristics of the Virtual Private Network (VPN) connection built under Android platform,analyzes whether VPN application has potential security risks by combining static analysis with dynamic verification,and introduces the detection result.

Hmgn5 functions downstream of Hoxa10 to regulate uterine decidualization in mice.

Although Hmgn5 is involved in the regulation of cellular proliferation and differentiation, its physiological function during decidualization is still unknown. Here we showed that Hmgn5 was highly expressed in the decidual cells. Silencing of Hmgn5 expression by specific siRNA reduced the proliferation of uterine stromal cells and expression of Ccnd3 and Cdk4 in the absence or presence of estrogen and progesterone, whereas overexpression of Hmgn5 exhibited the opposite effects. Simultaneously, Hmgn5 might induce the expression of Prl8a2 and Prl3c1 which were 2 well-known differentiation markers for decidualization. In the uterine stromal cells, cAMP analog 8-Br-cAMP and progesterone could up-regulate the expression of Hmgn5, but the up-regulation was impeded by H89 and RU486, respectively. Attenuation of Hmgn5 expression could block the differentiation of uterine stromal cells in response to cAMP and progesterone. Further studies found that regulation of cAMP and progesterone on Hmgn5 expression was mediated by Hoxa10. During in vitro decidualization, knockdown of Hmgn5 could abrogate Hoxa10-induced upregulation of Prl8a2 and Prl3c1, while overexpression of Hmgn5 reversed the inhibitory effects of Hoxa10 siRNA on the expression of Prl8a2 and Prl3c1. In the stromal cells undergoing decidualization, Hmgn5 might act downstream of Hoxa10 to regulate the expression of Cox-2, Vegf and Mmp2. Collectively, Hmgn5 may play an important role during mouse decidualization.

Association of coronary artery calcium with bone mineral density in postmenopausal women.

OBJECTIVES: Atherosclerosis and osteoporosis (OP) are common diseases in elderly individuals and may share common pathogenetic mechanisms. The aim of this study was to investigate the association between bone mineral density (BMD) and coronary artery calcium (CAC) in postmenopausal women. METHODS: In this cross-sectional study, 186 postmenopausal women 50-80 years of age were included. BMD of the spine and femoral neck was measured by dual-energy X-ray absorptiometry. The coronary artery calcium score (CACS) was measured by multidetector computed tomography. RESULTS: The study included postmenopausal women aged 65.6±7.3 years, 109 of whom (58.6%) showed CAC. Thirty-three (17.7%) of the patients were found to have OP in the lumbar spine and 83 (44.6%) had osteopenia, whereas in the femoral neck, 26 patients (14.0%) had OP and 87 patients (46.8%) had osteopenia. The mean CACS was 57.6±108.3 in normal status, 89.7±143.5 in OP, and 156.4±256.9 in osteopenia at the spine (P<0.05). The mean CACS was 43.2±89.9 in normal status, 126.9±180.3 in OP, and 198.2±301.2 in osteopenia at the femoral neck (P<0.05). Multivariable logistic regression analysis showed that BMD was an independent marker for an increased risk of developing CAC in postmenopausal women. The multiple regression model showed that T-scores were the independent predictors of CACS. CONCLUSION: BMD identified on images from dual-energy X-ray absorptiometry were strongly related to multidetector computed tomography measures of CAC. This low-cost, minimal radiation technique used widely for OP screening is a promising marker of generalized coronary atherosclerosis.

Runx2 acts downstream of C/EBPß to regulate the differentiation of uterine stromal cells in mice.

Although Runx2 is involved in the regulation of cellular differentiation, its physiological roles in the differentiation of uterine stromal cells during decidualization still remain unknown. The aim of this study was to examine the expression, regulation and function of Runx2 in mouse uterus during decidualization. The results showed that Runx2 was highly expressed in the decidua and oil-induced decidualized cells. In the uterine stromal cells, recombinant human Runx2 (rRunx2) could induce the expression of Prl8a2 and Prl3c1 which are two well-known differentiation markers for decidualization, while inhibition of Runx2 with specific siRNA reduced their expression. Further study found that rRunx2 could improve the expression of Prl8a2 and Prl3c1 in the C/EBPß siRNA-transfected stromal cells. In the stromal cells, cAMP analogue 8-Br-cAMP could induce the expression of Runx2. Moreover, the induction was blocked by PKA inhibitor H89. Simultaneously, attenuation of C/EBPß with siRNA could also reduce the cAMP-induced Runx2 expression. Furthermore, siRNA-mediated silencing of Runx2 expression alleviated the effects of cAMP on the differentiation of stromal cells. Runx2 might act downstream of C/EBPß to regulate the expression of Cox-2, Vegf and Mmp9 in the uterine stromal cells. Collectively, Runx2 may play an important role during mouse decidualization.