Clinical value of dual-energy CT for predicting occult metastasis in central neck lymph nodes of papillary thyroid carcinoma.

OBJECTIVES: To predict the probability of occult lymph node metastasis (OLNM) in the central cervical by analyzing the dual-energy computed tomography (DECT) parameters derived from papillary thyroid carcinoma (PTC). METHODS: Data were retrospectively collected from patients with pathologically confirmed PTC who underwent arterial and venous phases of enhanced DECT with concurrent central neck lymph node dissection (CLND). Three clinical features, three shape-related features, and twenty-six DECT-derived parameters were measured. The univariate and multivariate analyses were applied to select the relevant parameters and develop the nomogram. RESULTS: A total 140 cases with negative diagnosis of cervical central lymph node metastases by preoperative evaluation were included, among which 88 patients with metastasis (OLNM +) and 52 patients without metastasis (OLNM -) were finally confirmed by pathology. (1) Anteroposterior/transverse diameter ratio (A/T) derived from the PTC focus had significant difference between the OLNM + and OLNM - groups (p < 0.05). (2) In the arterial phase, iodine concentration (ICarterial), normalized iodine concentration (NICarterial), effective atomic number (Zeff-arterial), electron density (EDarterial), and slope of energy curve (karterial) from PTC focus showed significant difference (all p < 0.05) between the two groups. In the venous phase, only the CT value under the 40 keV (HU40keVvenous) had differences (p < 0.05). (3) The nomogram was produced to predict the probability of OLNM, and the AUC, sensitivity, and specificity in the training and test cohort were 0.830, 75.0%, 76.9%, and 0.829, 65.9%, 84.6%, respectively. CONCLUSIONS: DECT parameters combined with shape-related feature derived from PTC might be used as predictors of OLNM in the central neck. CLINICAL RELEVANCE STATEMENT: Preoperative imaging evaluation combining shape-related features and dual-energy CT parameters could serve as a reference to discern occult lymph node metastasis in central neck during the surgically planning of papillary thyroid carcinoma. KEY POINTS: • Papillary thyroid carcinoma (PTC) patients may have occult lymph node metastasis (OLNM) in the central neck, which is extremely difficult to find by preoperative imaging examination. • Dual-energy CT quantitative evaluation has higher accuracy than conventional CT and can predicting OLNM in the central neck of PTC. • Dual-energy CT quantitative parameters and morphology of PTC can serve as a useful tool in predicting OLNM in the central neck, and as a guide for personalized treatment.

Radiomics from dual-energy CT-derived iodine maps predict lymph node metastasis in head and neck squamous cell carcinoma.

OBJECTIVE: To develop and validate an iodine maps-based radiomics nomogram for preoperatively predicting cervical lymph node metastasis (LNM) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: A total of 278 patients who pathologically confirmed as HNSCC were retrospectively recruited from two medical centers between June 2012 and July 2022. The training set (n = 152) and internal set (n = 67) were randomly selected from medical center A, and the patients from medical center B were enrolled as the external set (n = 69). The minority group in the training set was balanced by the adaptive synthetic sampling (ADASYN) approach. Radiomics features were extracted from dual-energy CT-derived iodine maps at arterial phase (AP) and venous phase (VP), respectively. Three radiomics signatures were constructed to predict the LNM by using a random forest algorithm. The independent clinical predictors for LNM were identified by multivariate analysis and combined with radiomics signatures to establish a radiomic-clinical nomogram. The performance of radiomic-clinical nomogram was evaluated with respect to its discrimination and clinical usefulness. RESULTS: The AP-VP-incorporated radiomics model exhibited a great predictive performance for LNM prediction with an area under curve (AUC) of 0.885 (95% CI, 0.836-0.933) in ADASYN-training set and confirmed in all validation sets. The nomogram that incorporated AP-VP radiomics signatures, CT-reported LN status, and histological grades yielded AUCs of 0.920 (95% CI, 0.881-0.959) in ADASYN-training set, 0.858 (95% CI, 0.771-0.944) in internal validation, and 0.849 (95% CI, 0.752-0.946) in external validation, with good calibration in all cohorts (p > 0.05). Decision curve analyses indicated the nomogram was clinically useful. In addition, the predictive performance of clinical-radiomics nomogram was also validation in combing cohorts. Stratified analysis confirmed the stability of nomogram, particularly in group negative for CT-reported LNM. CONCLUSION: Clinical-radiomics nomogram based on iodine maps exhibited promising performance in predicting LNM and providing valuable information for making individualized therapy decisions.

CXCR4 blockade in macrophage promotes angiogenesis in ischemic hindlimb by modulating autophagy.

Chemokine receptor CXCR4 plays a crucial role in leukocyte recruitment and inflammation regulation to influence tissue repair in ischemic diseases. Here we assessed the effect of CXCR4 expression in macrophages on angiogenesis in the ischemic hindlimb of a mouse. Inflammatory cells were increased in the ischemic muscles of hindlimb, and CXCR4 was highly expressed in the infiltrated macrophages but not in neutrophils. Myeloid-specific CXCR4 knockout attenuated macrophage infiltration and subsequent reduced inflammatory response in the ischemic hindlimb, accompanied with better blood reperfusion and higher capillary density as compared with that in LysM Cre+/- (Cre) mice. Similar outcomes were also observed in CRE mice whose bone marrow cells were replaced with those from CXCR4-deficient mice. Gene ontology cluster analysis reviewed that Decorin, a negative regulator of angiogenesis, was reduced in CXCR4-deficient macrophages. CXCR4-deficient macrophages were less inducible into M1 phase by lipopolysaccharide and more favorable for M2 polarization under oxygen/glucose deprivation condition. Enhanced autophagy was detected in CXCR4-deficient macrophages, which was associated with less expression of both Decorin and the inflammatory cytokines. In summary, myeloid-specific CXCR4 deficiency reduced monocyte infiltration and the secretion of inflammatory cytokines and Decorin from macrophages, thus blunting inflammation response and promoting angiogenesis in the ischemic hindlimb.

Cardiac ankyrin repeat protein contributes to dilated cardiomyopathy and heart failure.

Cardiac ankyrin repeat protein (CARP) is a cardiac-specific stress-response protein which exerts diverse effects to modulate cardiac remodeling in response to pathological stimuli. We examined the role of CARP in postnatal cardiac development and function under basal conditions in mice. Transgenic mice that selectively overexpressed CARP in heart (CARP Tg) exhibited dilated cardiac chambers, impaired heart function, and cardiac fibrosis as assessed by echocardiography and histological staining. Furthermore, the mice had a shorter lifespan and reduced survival rate in response to ischemic acute myocardial infarction. Immunofluorescence demonstrated the overexpressed CARP protein was predominantly accumulated in the nuclei of cardiomyocytes. Microarray analysis revealed that the nuclear localization of CARP was associated with the suppression of calcium-handling proteins. In vitro experiments revealed that CARP overexpression resulted in decreased cell contraction and calcium transient. In post-mortem cardiac specimens from patients with dilated cardiomyopathy and end-stage heart failure, CARP was significantly increased. Taken together, our data identified CARP as a crucial contributor in dilated cardiomyopathy and heart failure which was associated with its regulation of calcium-handling proteins.

Genetic liability to sedentary behavior in relation to myocardial infarction and heart failure: A mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have indicated that sedentary behavior is associated with myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). Nevertheless, whether these associations are causal remain controversial, due to confounding factors (e.g., physical activity) and reverse causality. METHODS AND RESULTS: Instrumental variables were obtained from the largest genome-wide association studies of sedentary behavior (408,815 individuals) to date. We obtained summary statistics of MI from the CARDIoGRAMplusC4D consortium (171,875 individuals), HF from the HERMES Consortium (977,323 individuals), and AF from the Atrial Fibrillation Consortium (588,190 individuals). The inverse-variance weighted method was applied to obtain Mendelian randomization (MR) estimates, and other statistical methods were conducted in the sensitivity analyses. The main analyses were repeated using data from the FinnGen study. Multivariable MR analysis and mediation analysis were performed to evaluate the role of physical activity and other confounders. Genetically determined television watching was associated with MI (odds ratio [OR], 1.38; 95% CI, 1.19-1.59; p = 1.9 × 10-5) and HF (OR, 1.23; 95%CI, 1.09-1.38; p = 7.0 × 10-4) but not AF. The main results kept robust in most sensitivity analyses. The effect of sedentary behavior on MI and HF was partly mediated by body mass index (BMI). No consistent evidence was found for the causal effect of computer use and driving on MI, HF, or AF. CONCLUSIONS: Genetic liability to prolonged television watching is associated with higher risks of MI and HF. Interventions for reducing television watching time, such as public education and awareness campaigns, should be further investigated.

Joint application of hybrid iterative reconstruction and adaptive filters on neck-and-shoulder CT imaging: A clinical evaluation.

PURPOSE: To assess whether the joint application of hybrid iterative reconstruction (HIR) and an adaptive filter (AF) could reduce streak artifacts and improve image quality of neck-and-shoulder computed tomography (CT). METHODS: This study included 96 patients with suspicious neck lesions who underwent a routine nonenhanced scan on a 64-slice CT scanner. The raw data were reconstructed using four different settings: filtered back projection (FBP), HIR, FBP + AF, and HIR + AF. Regions of interest were manually drawn in erector spine, axillary fat, latissimus dorsi, and dorsal cervical fat. Mean and standard deviation (SD) of the CT number, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were obtained and compared using Wilcoxon signed-rank tests. The qualitative assessments of five factors were compared by two independent investigators. RESULTS: Compared to the other three settings, HIR + AF reduced noise in the area where the streak artifact of the lower neck were most serious (SD; all p ≤ 0.001). The SNR and CNR were improved significantly (all p ≤ 0.001). Compared to the other three settings, HIR + AF showed a significant improvement in CT image quality regarding the visibility of suspicious lesions, the extent of streaking artifacts, noise, soft-tissue contrast, and visualization of small structures (all p ≤ 0.02). CONCLUSIONS: The combination of HIR and AF can significantly reduce streaking artifacts and improve image quality in neck-and-shoulder CT imaging.

PBL teaching in ultrasonography resident standardization training in the COVID-19 pandemic.

OBJECTIVE: To study the effect of the problem-based learning (PBL) method in ultrasonography (US) resident standardization training during the COVID-19 pandemic. METHODS: Fifty residents were divided into two groups to participate in a 30-day US training program. The residents in the observation group underwent PBL combined with the lecture-based learning (LBL) method, while the residents in the control group experienced the LBL method alone, with 25 residents in each group. A basic theoretical test, practical examination, and questionnaire were used to evaluate the teaching effect of the PBL + LBL method and the LBL method alone. RESULTS: The basic theoretical pretest score of the observation group was not significantly different from that of the control group. However, the posttest theoretical score and practical score were significantly higher in the observation group than in the control group (P < 0.01). The results of the questionnaire showed that the resident satisfaction level in the observation group with PBL combined with the LBL method was 96%, which was significantly higher than that of the control group with the LBL method alone (80%) (P < 0.05). CONCLUSION: The combination of PBL with the LBL method has obvious advantages over the LBL method alone in regard to the training of US residents during the COVID-19 pandemic.

Genome-Wide Identification and Expression Analysis of the 14-3-3 Gene Family in Mango (Mangifera indica L.).

Members of the Mi14-3-3 gene family interact with target proteins that are widely involved in plant hormone signal transduction and physiology-related metabolism and play important roles in plant growth, development and stress responses. In this study, 14-3-3s family members are identified by the bioinformatic analysis of the mango (Mangifera indica L.) genome. The gene structures, chromosomal distributions, genetic evolution, and expression patterns of these genes and the physical and chemical properties and conserved motifs of their proteins are analysed systematically. The results identified 16 members of the 14-3-3 genes family in the mango genome. The members were not evenly distributed across the chromosomes, and the gene structure analysis showed that the gene sequence length and intron number varied greatly among the different members. Protein sequence analysis showed that the Mi14-3-3 proteins had similar physical and chemical properties and secondary and tertiary structures, and protein subcellular localization showed that the Mi14-3-3 family proteins were localized to the nucleus. The sequence analysis of the Mi14-3-3s showed that all Mi14-3-3 proteins contain a typical conserved PFAM00244 domain, and promoter sequence analysis showed that the Mi14-3-3 promoters contain multiple hormone-, stress-, and light-responsive cis-regulatory elements. Expression analysis showed that the 14-3-3 genes were expressed in all tissues of mango, but that their expression patterns were different. Drought, salt and low temperature stresses affected the expression levels of 14-3-3 genes, and different 14-3-3 genes had different responses to these stresses. This study provides a reference for further studies on the function and regulation of Mi14-3-3 family members.

CCL7 contributes to angiotensin II-induced abdominal aortic aneurysm by promoting macrophage infiltration and pro-inflammatory phenotype.

Chemokine C-C motif ligand 7 (CCL7), a member of CC chemokine subfamily, plays pivotal roles in numerous inflammatory diseases. Hyper-activation of inflammation is an important characteristic of abdominal aortic aneurysm (AAA). Therefore, in the present study, we aimed to determine the effect of CCL7 on AAA formation. CCL7 abundance in aortic tissue and macrophage infiltration were both increased in angiotensin II (Ang II)-induced AAA mice. Ex vivo, CCL7 promoted macrophage polarization towards M1 phenotype. This effect was reversed by the blockage of CCR1, a receptor of CCL7. CCL7 up-regulated JAK2/STAT1 protein level in macrophage, and CCL7-induced M1 activation was suppressed by JAK2/STAT1 pathway inhibition. To verify the effect of CCL7 on AAA in vivo, either CCL7-neutralizing antibody (CCL7-nAb) or vehicles were intraperitoneally injected 24 hours prior to Ang II infusion and subsequently every three days for 4 weeks. CCL7-nAb administration significantly attenuated Ang II-induced luminal and external dilation as well as pathological remodelling. Immunostaining showed that CCL7-nAb administration significantly decreased aneurysmal macrophage infiltration. In conclusion, CCL7 contributed to Ang II-induced AAA by promoting M1 phenotype of macrophage through CCR1/JAK2/STAT1 signalling pathway.

Overexpression of four MiTFL1 genes from mango delays the flowering time in transgenic Arabidopsis.

BACKGROUND: TERMINAL FLOWER 1 (TFL1) belongs to the phosphatidylethanolamine-binding protein (PEBP) family, which is involved in inflorescence meristem development and represses flowering in several plant species. In the present study, four TFL1 genes were cloned from the mango (Mangifera indica L.) variety 'SiJiMi' and named MiTFL1-1, MiTFL1-2, MiTFL1-3 and MiTFL1-4. RESULTS: Sequence analysis showed that the encoded MiTFL1 proteins contained a conserved PEBP domain and belonged to the TFL1 group. Expression analysis showed that the MiTFL1 genes were expressed in not only vegetative organs but also reproductive organs and that the expression levels were related to floral development. Overexpression of the four MiTFL1 genes delayed flowering in transgenic Arabidopsis. Additionally, MiTFL1-1 and MiTFL1-3 changed the flower morphology in some transgenic plants. Yeast two-hybrid (Y2H) analysis showed that several stress-related proteins interacted with MiTFL1 proteins. CONCLUSIONS: The four MiTFL1 genes exhibited a similar expression pattern, and overexpression in Arabidopsis resulted in delayed flowering. Additionally, MiTFL1-1 and MiTFL1-3 overexpression affected floral organ development. Furthermore, the MiTFL1 proteins could interact with bHLH and 14-3-3 proteins. These results indicate that the MiTFL1 genes may play an important role in the flowering process in mango.

Ectopic thyroid tissue: An unusual cause of intracardiac mass.

Intracardiac ectopic thyroid tissue is an extremely rare condition, with only 37 cases reported in the English literature. We present a case of intracardiac ectopic thyroid adenoma and briefly review the published reports.

Isolation and Functional Characterization of Two SHORT VEGETATIVE PHASE Homologous Genes from Mango.

The SHORT VEGETATIVE PHASE (SVP) gene is a transcription factor that integrates flowering signals and plays an important role in the regulation of flowering time in many plants. In this study, two full-length cDNA sequences of SVP homologous genes-MiSVP1 and MiSVP2-were obtained from 'SiJiMi' mango. Sequence analysis showed that the MiSVPs had typical MADS-box domains and were highly conserved between each other. The analysis of expression patterns showed that the MiSVPs were expressed during flower development and highly expressed in vegetative tissues, with low expression in flowers/buds. The MiSVPs could responded to low temperature, NaCl, and PEG treatment. Subcellular localization revealed that MiSVP1 and MiSVP2 were localized in the nucleus. Transformation of Arabidopsis revealed that overexpression of MiSVP1 delayed flowering time, overexpression of MiSVP2 accelerated flowering time, and neither MiSVP1 nor MiSVP2 had an effect on the number of rosette leaves. Overexpression of MiSVP1 increased the expression of AtFLC and decreased the expression of AtFT and AtSOC1, and overexpression of MiSVP2 increased the expression levels of AtSOC1 and AtFT and decreased the expression levels of AtFLC. Point-to-point and bimolecular fluorescence complementation (BiFC) assays showed that MiSVP1 and MiSVP2 could interact with SEP1-1, SOC1D, and AP1-2. These results suggest that MiSVP1 and MiSVP2 may play a significant roles in the flowering process of mango.

Insight into the Pro-inflammatory and Profibrotic Role of Macrophage in Heart Failure With Preserved Ejection Fraction.

The prevalence of heart failure (HF) with preserved ejection fraction (HFpEF) is higher than that of HF with reduced/midrange ejection fraction (HFrEF/HFmrEF). However, no evidence-based guidelines for managing HFpEF have been generated. The current body of knowledge indicates that fibrosis and inflammation are important components of the cardiac remodeling process in HFpEF. In addition, macrophages potentially play an important role in pro-inflammatory and profibrotic processes in HFpEF patients, whereas HFpEF comorbidities could be a driving force for systemic microvascular inflammation and endothelial dysfunction. Under such circumstances, macrophages reportedly contribute to inflammation and fibrosis through 3 phases namely, inflammation, repair, and resolution. Signal transduction pathway-targeted therapies using animal experiments have generated important discoveries and breakthroughs for understanding the underlying mechanisms of HFpEF. However, only a handful of studies have reported promising results using human trials. Further investigations are therefore needed to elucidate the exact mechanisms underlying HFpEF and immune-pathogenesis of cardiac fibrosis.

The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian randomization study.

BACKGROUND: Growth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor ß cytokine superfamily. Some evidence support that it's involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it's still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence. METHODS: Genetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses. RESULTS: Among 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. CONCLUSIONS: The MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.

The risk of bleeding for antiplatelet agents in Haemodialysis patients: a Meta-analysis.

BACKGROUND: The safety of antiplatelet therapy in haemodialysis (HD) patients remains controversial. we conducted the first meta-analysis to evaluate the bleeding risk with antiplatelet agents in these populations. METHODS: The relevant literature was searched using the following electronic databases without any language restrictions: the Cochrane Library, EMBASE, Global Health, MEDLINE, PubMed, and the Chinese Biomedical Database. RESULTS: Seven randomized controlled trials (RCTs) and 2 prospective cohort studies, consisting of 1131 patients, were identified for detailed evaluation. The meta-analysis suggested that the use of double antiplatelet agents increased the risk of bleeding in HD patients [odds ratio (OR) = 2.78; 95% confidence interval (CI) 1.63 to 4.76; I2 = 0], and antiplatelet agents increased the risk of bleeding in 7 RCTs [odds ratio (RR) = 1.40, 95% CI 1.08 to 1.79; I2 = 23%,]; however, the use of a single antiplatelet agent was not found to significantly increase the risk of bleeding (RR = 0.88; 95% CI 0.51 to 1.50; I2 = 0). CONCLUSION: The results suggested that the use of double antiplatelet agents increased the risk of bleeding in HD patients.

Ginkgo biloba extracts prevent aortic rupture in angiotensin II-infused hypercholesterolemic mice.

Abdominal aortic aneurysms (AAAs) are a chronic vascular disease characterized by pathological luminal dilation. Aortic rupture is the fatal consequence of AAAs. Ginkgo biloba extracts (GBEs), a natural herb extract widely used as food supplements, drugs, and cosmetics, has been reported to suppress development of calcium chloride-induced AAAs in mice. Calcium chloride-induced AAAs do not rupture, while angiotensin II (AngII)-induced AAAs in mice have high rate of aortic rupture, implicating potentially different mechanisms from calcium chloride-induced AAAs. This study aimed to determine whether GBE would improve aortic dilation and rupture rate of AngII-induced AAAs. Male apolipoprotein E (apoE) -/- mice were infused with AngII and administered either GBE or its major active ingredients, flavonoids and ginkgolides, individually or in combination. To determine the effects of GBE in mice with established AAAs, male apoE-/- mice were firstly infused with AngII for 28 days to develop AAAs, and then administered either GBE or vehicle in mice with established AAAs, which were continuously infused with AngII for another 56 days. GBE, but not the two major active components separately or synergistically, prevented aortic rupture, but not aortic dilation. The protection of GBE from aortic rupture was independent of systolic blood pressure, lipid, and inflammation. GBE also did not attenuate either aortic rupture or progressive aortic dilation in mice with established AAAs. GBE did not reduce the atherosclerotic lesion areas, either. In conclusion, GBE prevents aortic rupture in AngII-infused hypercholesterolemic mice, but only in the early phase of the disease development.

[Prenatal diagnosis of a fetus with trisomies of 11q23.3q25 and 22q11.1q11.21].

OBJECTIVE: To explore the phenotype and pathogenesis of a fetus with a rare chromosomal abnormality. METHODS: The fetus was analyzed by clinical prenatal ultrasonography, G-banding karyotyping and next generation sequencing (NGS). RESULTS: Prenatal ultrasonography of the fetus showed Dandy-Walker syndrome, growth restriction, and right-heart system dysplasia. The fetus had a chromosomal karyotype of 47,XY,t(11;22)(q23.3;q11.2),+der(22)t(11;22). Duplication of 11q23.3q25 and 22q11.1q21 were also detected by NGS. The chromosomal translocation carried by the fetus was derived from his father. CONCLUSION: Duplications of chromosome 11q23.3q25 and 22q11.1q11.21 segments probably underlie the Dandy-Walker syndrome, growth restriction, and hypoplasia of the right heart system in the fetus.

Triterpenoid Saponins from Anemone rivularis var. Flore-Minore and Their Anti-Proliferative Activity on HSC-T6 Cells.

Five previously undescribed triterpenoid saponins (1-5), along with eight known ones (6-13), were isolated from the whole plants of Anemone rivularis var. flore-minore. Their structures were clarified by extensive spectroscopic data and chemical evidence. For the first time, the lupane-type saponins (3 and 12) were reported from the Anemone genus. The anti-proliferative activity of all isolated saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13, which possess more monosaccharides than the others, displayed potent anti-proliferative activity, with IC50 values of 18.21 and 15.56 µM, respectively.

Cardiac ankyrin repeat protein attenuates cardiomyocyte apoptosis by upregulation of Bcl-2 expression.

Cardiac ankyrin repeat protein (CARP) is a nuclear transcriptional co-factor that has additional functions in the myoplasm as a component of the muscle sarcomere. Previous studies have demonstrated increased expression of CARP in cardiovascular diseases, however, its role in cardiomyocyte apoptosis is unclear and controversial. In the present study, we investigated possible roles of CARP in hypoxia/reoxygenation (H/R) -induced cardiomyocyte apoptosis and the underlying mechanisms. Neonatal mouse ventricular cardiomyocytes were isolated and infected with adenovirus encoding Flag-tagged CARP (Ad-CARP) and lentivirus encoding CARP targeted shRNA (sh-CARP), respectively. Cardiomyocyte apoptosis induced by exposure to H/R conditions was evaluated by TUNEL staining and western blot analysis of cleaved caspase-3. The results showed that H/R-induced apoptosis was significantly decreased in Ad-CARP cardiomyocytes and increased in sh-CARP cardiomyocytes, suggesting a protective anti-apoptosis role for CARP. Interestingly, over-expressed CARP was mainly distributed in the nucleus, consistent with its role in regulating transcriptional activity. qPCR analysis showed that Bcl-2 transcripts were significantly increased in Ad-CARP cardiomyocytes. ChIP and co-IP assays confirmed the binding of CARP to the Bcl-2 promoter through interaction with transcription factor GATA4. Collectively, our results suggest that CARP can protect against H/R induced cardiomyocyte apoptosis, possibly through increasing anti-apoptosis Bcl-2 gene expression.