Pulmonary embolism in patients with chronic coronary syndrome masquerading as acute coronary syndrome: a case report and literature review.

BACKGROUND: Pulmonary embolisms (PEs) exhibit clinical features similar to those of acute coronary syndrome (ACS), including electrocardiographic abnormalities and elevated troponin levels, which frequently lead to misdiagnoses in emergency situations. CASE PRESENTATION: Here, we report a case of PE coinciding with chronic coronary syndrome in which the patient's condition was obscured by symptoms mimicking ACS. A 68-year-old female with syncope presented to the hospital. Upon admission, she was found to have elevated troponin levels and an electrocardiogram showing ST-segment changes across multiple leads, which initially led to a diagnosis of ACS. Emergency coronary arteriography revealed occlusion of the posterior branches of the left ventricle of the right coronary artery, but based on the complexity of the intervention, the occlusion was considered chronic rather than acute. On the 3rd day after admission, the patient experienced recurrent chest tightness and shortness of breath, which was confirmed as acute PE by emergency computed tomography pulmonary angiography. Following standardized anticoagulation treatment, the patient improved and was subsequently discharged. CONCLUSIONS: This case report highlights the importance of recognizing the nonspecific features of PE. Clinicians should be vigilant when identifying other clinical features that are difficult to explain accompanying the expected disease, and it is necessary to carefully identify the causes to prevent missed diagnoses or misdiagnoses.

Causal relationship between nutritional assessment phenotypes and heart failure: A Mendelian randomization study.

Introduction: Malnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors. Methods: Two-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations. Results: Three phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60-1.90; P = 3.95 × 10-39), body mass index (BMI) (OR = 1.70; 95%CI, 1.60-1.80; P = 1.35 × 10-73), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44-1.65; P = 4.82 × 10-37). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27-3.31; P = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27-0.60; P = 8.41 × 10-6), educational attainment (EA) (OR = 0.73; 95%CI, 0.67-0.79; P = 2.27 × 10-13), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84-0.96; P = 4.22 × 10-3). There was a bidirectional causality between HF and UWP (Effect estimate = -0.03; 95%CI, -0.05 to -0.01; P = 1.95 × 10-3). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P < 0.05). Conclusions: BMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes.

Comprehensive analysis of cuproptosis-related long non-coding RNAs in prognosis, immune microenvironment infiltration and chemotherapy response of hepatocellular carcinoma.

The objective of this study is to explore the relationship between cuproptosis-related long noncoding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). RNA-seq data, including lncRNAs and related clinical information of HCC patients, were downloaded from The Cancer Genome Atlas database. A signature composed 3 cuproptosis-related lncRNAs was constructed by LASSO analysis, and HCC patients were classified into high- and low-risk groups. Patients in the high-risk group had a poorer prognosis compared with the low-risk group. Univariate Cox and multivariate Cox regression analyses confirmed that the signature model was an independent risk factor compared to other clinical biomarkers. Furthermore, gene set enrichment analysis indicated that metabolism-related pathways were enriched in low-risk group, including drug metabolism, and fatty acid metabolism. Further research demonstrated that there were markedly differences in drug response between the high- and low-risk group. Immune related analysis showed that the most type of immune cells and immunological function in the high-risk group were different with the risk-group. Finally, TP53 mutation rate and the tumor mutational burden in the high-risk group were higher compared with the low-risk group. In conclusion, we constructed a prognostic signature based on the expression of cuproptosis-related lncRNAs to predict HCC patients' prognosis, drug response and immune microenvironment, and further research will be conducted to uncover the mechanisms.

Morphinan and isoquinoline alkaloids from the tuberous roots of Stephania cepharantha.

A new morphinan alkaloid (6S, 9S, 13 R, 14S)-6-O-acetyl-7,8-Didehydro-4-hydroxy-3,7-dimethoxymorphinan-6-ol (1), and a new naturally occurring cularine alkaloid (S)-2, 3, 12, 12a-tetrahydro-5, 6, 9, 10-tetramethoxy-1-methyl-1H-[1]benzoxepino[2, 3, 4-ij]isoquinoline(5), along with four known alkaloids were isolated from the roots of Stephania cepharantha. The structures of these compounds were elucidated based on spectroscopic data analyses. Cytotoxic activities of the compounds against three human cancer cell lines (A549, MCF-7 and SW480) were also evaluated.

Bibliometric analysis of traditional Chinese medicine research on heart failure in the 21st century based on the WOS database.

Introduction: Heart Failure (HF) is a key area of research in human medicine, and traditional Chinese medicine (TCM) is an important branch of this field. This study aimed to use bibliometric methods to sort out the trajectory of TCM research on HF in this century (2000-2022) from a high dimension and to analyze its characteristics, hotspots and frontiers. Methods: In this study, the search formula "TS=(("traditional Chinese medicine") OR ("Chinese medicine")) AND TS=("heart failure")" was used to find relevant studies included in the Web of Science Core Collection from 2000 to 2022. Targeted literature records were analyzed and mapped using CiteSpace and VOSviewer. Results: The authors and collaborators of this study were still in the formation process, but several well-known scholars were included: YONG WANG, WEI WANG, etc. The main research institutions in this research area were Beijing Univ Chinese Med, China Acad Chinese Med Sc, etc. The main country of study was China. Current research hotspots and frontiers were Qili Qiangxin capsules, extracts (Tanshinone ⅡA, Panax ginseng, etc.), cardiac hypertrophy, ventricular remodeling, oxidative stress, signaling pathways, network pharmacology, etc. Influential journals that publish papers in this field were the Journal of Ethnopharmacology, Scientific Reports, Biomedicine & Pharmacotherapy, etc. The top 3 co-cited journals were Circulation, J ethnopharmacol, and J am coll cardiol. Conclusions: We analyzed valuable details in TCM research on HF in the 21st century, which may help researchers identify potential collaborators and partner institutions, hotspots, and frontiers in the field.

Predicting the Number of Reported Pulmonary Tuberculosis in Guiyang, China, Based on Time Series Analysis Techniques.

Tuberculosis (TB) is one of the world's deadliest infectious disease killers today, and despite China's increasing efforts to prevent and control TB, the TB epidemic is still very serious. In the context of the COVID-19 pandemic, if reliable forecasts of TB epidemic trends can be made, they can help policymakers with early warning and contribute to the prevention and control of TB. In this study, we collected monthly reports of pulmonary tuberculosis (PTB) in Guiyang, China, from January 1, 2010 to December 31, 2020, and monthly meteorological data for the same period, and used LASSO regression to screen four meteorological factors that had an influence on the monthly reports of PTB in Guiyang, including sunshine hours, relative humidity, average atmospheric pressure, and annual highest temperature, of which relative humidity (6-month lag) and average atmospheric pressure (7-month lag) have a lagging effect with the number of TB reports in Guiyang. Based on these data, we constructed ARIMA, Holt-Winters (additive and multiplicative), ARIMAX (with meteorological factors), LSTM, and multivariable LSTM (with meteorological factors). We found that the addition of meteorological factors significantly improved the performance of the time series prediction model, which, after comprehensive consideration, included the ARIMAX (1,1,1) (0,1,2)12 model with a lag of 7 months at the average atmospheric pressure, outperforms the other models in terms of both fit (RMSE = 37.570, MAPE = 10.164%, MAE = 28.511) and forecast sensitivity (RMSE = 20.724, MAPE = 6.901%, MAE = 17.306), so the ARIMAX (1,1,1) (0,1,2)12 model with a lag of 7 months can be used as a predictor tool for predicting the number of monthly reports of PTB in Guiyang, China.

Literature review of imaging, pathological diagnosis, and outcomes of metachronous lung and pancreatic metastasis of cecal cancer.

BACKGROUND: Pancreatic metastasis from colorectal cancer is extremely rare. Here, we report a case of colorectal cancer with lung and pancreatic metastasis and analyze the histopathology, immunohistochemistry, and next-generation sequencing (NGS) to generate a differential diagnosis and treatment of metastatic colon cancer. CASE PRESENTATION: AC1 A 78-year-old man was admitted because of a recently elevated carcinoembryonic antigen. This patient had undergone laparoscopic right hemicolectomy for cecal cancer IIA (T3N0M0) 5 years before admission, and thoracoscopic left upper lung wedge resection for primary colon cancer lung metastasis 2 years before admission. At that time, the patient was thought to have pancreatic metastasis from colon cancer. He underwent laparoscopic distal pancreatectomy (combined with splenectomy). Postoperative pathology revealed colon cancer metastasis. We performed NGS on tumor samples at three loci and found colon cancer's most common oncogenic driver genes (KRAS, APC, and TP53). One month after surgery, the patient was given capecitabine for six cycles of chemotherapy. At present, no high adverse reactions have been reported. DISCUSSION: For patients with pancreatic space-occupying, such as a previous history of colorectal cancer, and recent carcinoembryonic antigen elevation, we should highly suspect pancreatic metastatic colorectal cancer. NGS is an essential auxiliary for identifying metastatic tumors. Surgery combined with postoperative chemotherapy is an effective treatment.

Alkaloids from Aconitum carmichaelii Alleviates DSS-Induced Ulcerative Colitis in Mice via MAPK/NF-κB/STAT3 Signaling Inhibition.

Fuzi (Aconitum carmichaelii Debx) has been traditionally used for the treatment of ulcerative colitis (UC) in China for thousands of years. The total alkaloids of A. carmichaelii (AAC) have been considered as the main medicinal components of fuzi, whereas its underlying anti-UC mechanisms remain elusive. In the present study, the dextran sulfate sodium (DSS)-induced UC mice model, which was consistent with the symptoms and pathological features of human UC, was established to comprehensively evaluate the anti-UC effects of AAC. The results indicated that AAC effectively improved the weight loss, disease activity index (DAI), spleen hyperplasia, and colon shortening, and thus alleviated the symptoms of UC mice. Meanwhile, AAC not only inhibited the MPO enzyme and the abnormal secretion of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IFN-γ, and IL-17A) and suppressed the overexpression of inflammatory mediators (TNF-α, IL-1ß, and IL-6) of mRNA but also reduced the phosphorylation of p38 MAPK, ERK, and JNK, and the protein expressions of NF-κB, IκB-α, STAT3, and JAK2 in the colon tissue. Furthermore, the LC-MS/MS quantitative determination suggested that the three low toxic monoester alkaloids were higher in both contents and proportion than that of the three high toxic diester alkaloids. Additionally, molecular docking was hired to investigate the interactions between alkaloid-receptor complexes, and it suggested the three monoester alkaloids exhibited higher binding affinities with the key target proteins of MAPK, NF-κB, and STAT3. Our finding showcased the noteworthy anti-UC effects of AAC based on the MAPK/NF-κB/STAT3 signaling pathway, which would provide practical and edge-cutting background information for the development and utilization of A. carmichaelii as a potential natural anti-UC remedy.

Study on the Mechanism of Treating Femoral Head Necrosis with Drynariae Rhizoma Based on Network Pharmacology.

Through the network pharmacology thought, the action target of the active ingredients of Drynariae Rhizoma was predicted, and the mapping was combined with the related targets of ONFH, and the key nodes of interaction were identified for enrichment analysis, so as to comprehensively explore the pharmacological mechanism of Drynariae Rhizoma against ONFH. The main active ingredients of Drynariae Rhizoma were screened based on pharmacokinetic characteristics in pharmacokinetic database and analysis platform of TCM system (TCMSP). We used the organic small molecule bioactivity database (PubChem) and Swiss target prediction database to predict related targets based on 2D or 3D structural similarity and then mined the known ONFH therapeutic targets through the Human Mendelian Genetic Database (OMIM) and Pubmed texts. Combined with the predicted targets, String database was imported to construct the OP target interaction network diagram of bone fracture therapy. CytoNCA software was used to topology the key nodes of interaction according to relevant node parameters, and String was imported again to construct the protein interaction network diagram. Finally, biological functions and metabolic pathways of key nodes were analyzed through DAVID database. It was revealed that Drynariae Rhizoma may regulate stem cells, osteoblasts, osteoclasts, and immune cells through multiple pathways, including proliferation, differentiation, immunity, and oxidative stress. Conclusion: Pharmacological studies based on network indicate that Drynariae Rhizoma may participate in the regulation of several major signaling pathways through direct or indirect action targets and affect the proliferation and differentiation of multiple types of cells, thus playing an anti-ONFH role, which provides a scientific basis for explaining the material basis and mechanism of its anti- ONFH.

A Traditional Chinese Medicine Formula Danshen Baibixiao Ameliorates Imiquimod-Induced Psoriasis-Like Inflammation in Mice.

Background: Danshen Baibixiao (DB) is a traditional Chinese medicine formula, which has been used to treat psoriasis for decades. Although DB shows good efficacy in clinical practice, the pharmacological effects and underlying mechanisms of DB remain elusive. This study aimed to evaluate the anti-psoriatic effects of DB and explore its underlying mechanisms in an imiquimod (IMQ)-induced psoriasis-like mouse model. Materials and methods: DB was orally administered on IMQ-induced psoriatic mice. Psoriasis area severity index (PASI) was used to evaluate the severity of the inflammation in skin, and histological changes were evaluated by hematoxylin and eosin (H and E) staining. Levels of inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-17A, IL-23, IL-6, IL-1ß and IL-22 in serum were assessed by enzyme-linked immunosorbent assay (ELISA). mRNA expressions of IL-17A, IL-23, IL-6 and IL-22 were determined by real-time polymerase chain reaction (PCR). Expression levels of proteins related to NF-κB, STAT3 and MAPKs signaling pathways were measured by western blotting (WB). Results: DB significantly ameliorated the psoriatic symptoms in IMQ-induced mice. The serum levels of inflammatory cytokines (TNF-α, IL-17A, IL-23, IL-6, IL-1ß and IL-22) were decreased, and mRNA expressions of IL-17A, IL-23, IL-6 and IL-22 in skin tissues were down-regulated. Moreover, WB analysis indicated that DB inhibited the activation of NF-κB, STAT3 and MAPKs signaling pathways. Conclusion: This study confirms the anti-psoriatic activity of DB in IMQ-induced psoriasis-like mice. The possible mechanism may relate to the activities of regulating the IL-23/TH-17 axis and suppressing the activation of NF-κB, STAT3 and MAPKs signaling pathways.

Extended-aperture Hartmann wavefront sensor with raster scanning.

In this paper, we propose an extended-aperture Hartmann wavefront sensor (HWFS) based on raster scanning. Unlike traditional HWFS, where there is a trade-off between the dynamic range and spatial resolution of wavefront measurement, our extended-aperture HWFS breaks the trade-off and thus could achieve a large dynamic range and high spatial resolution simultaneously. By applying a narrow-beam raster-scanning scheme, the detection aperture of our HWFS is extended to 40 × 40 mm2 without using the enlarging 4f relay system. The spatial resolution of our setup depends on the scanning step, the pinhole size, and the wavelength. The sensitivity and dynamic range can be adjusted flexibly by varying the axial distance between the pinhole plane and the imaging sensor plane, because our decoupled large dynamic range could be reasonable traded-off to achieve better sensitivity. Furthermore, compared with tradition HWFS, our method does not need to compute the positions of a two-dimensional spots array where complicated spots tracking algorithms are necessary to achieve high dynamic range, thus remarkably reduces the spots aliasing issue and the computational cost. It should be noted that this scheme is not only applicable for HWFS but also for Shack-Hartmann wavefront sensor (SHWFS) with microlens array to achieve higher accuracy and better power efficiency. Experiments were performed to demonstrate the capability of our method.

Extended aperture line-scanning Hartmann wavefront sensor.

We first propose a line-scanning Hartmann wavefront sensor (LS-HWS) with extended aperture. In the LS-HWS, a line-scanning imaging sensor was driven by a motor and scanning behind a large-area Hartman mask. Compared to the traditional Hartman wavefront sensor with two-dimensional imaging sensors, our method can significantly enlarge the aperture because of the larger imaging area with line-scanning imaging sensors. Cross correlation registration was adopted to reduce the scanning error. Experiments on two single spherical lenses and a free-form lens were performed to demonstrate the capability of the LS-HWS method. The results show that our method can achieve an aperture of 17.5×37.5mm2 with the prototype system, which could be further extended easily and is limited only by the size of the line-scanning imaging sensor and the scanning range of the motor. We believe that the LS-HWS method is promising for many wavefront sensing applications where a large aperture is preferred.

MicroRNA-20b inhibits trophoblast cell migration and invasion by targeting MMP-2.

Insufficient trophoblast migration/invasion is associated with the preeclampsia (PE) development. Recently, microRNAs (miRNAs) have been confirmed to be involved in the pathogenesis of PE. The aim of the present study was to evaluate whether miRNAs is involved in the procession of PE by regulating the migration/invasion of trophoblast. First, we compared the expression profiles of miRNAs between normal and preeclamptic placentas using microarray. Validation analysis of miR-20b level in placentas and peripheral blood specimens was performed using quantitative reverse transcription PCR (qRT-PCR). Then, the effects of miR-20b on trophoblast cell migration and invasion were evaluated using wound healing assay and transwell migration assay. Further bioinformatics analysis, luciferase reporter assays and Western blot were performed to identify its target genes. The correlation between miR-20b and matrix metalloproteinase-2 (MMP-2) in placentas was determined by Pearson's correlation coefficient. Finally, HTR8/SVneo cells were co-transfected with miR-20b inhibitor and si-MMP-2 to explore the molecular mechanism by which miR-20b functions in the trophoblast migration/invasion. We found that miR-20b was elevated in placentas and peripheral blood specimens from preeclampsia patients. Further results show that overexpression of miR-20b significantly inhibited the invasiveness of human trophoblast cells, whereas miR-20b knockdown enhanced trophoblast cell invasion. Matrix metalloproteinase-2 (MMP-2), the most common enzymes in remodeling extracellular matrix components for metastasis, was proved to be a direct target of miR-20b. Inhibition of MMP-2 by siRNA could reverse the promoting effect of miR-20b inhibition on the invasion of trophoblast cells. Taken together, our study indicates that miR-20b inhibited trophoblastic invasion by targeting MMP2. The miR-20b/MMP-2 axis may provide novel insights into understanding the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for PE.

PGC-1 alpha interacts with microRNA-217 to functionally regulate breast cancer cell proliferation.

BACKGROUND: In this study, we explored the functional mechanism of PPARg co-activator 1-alpha (PGC-1α) in regulating miR-217-mediated breast cancer development in vitro. METHODS: Dual-luciferase activity assay was applied to examine the binding of miR-217 on PGC-1α gene. Breast cancer cell lines, MCF-7 and MDA-MB-231 were infected by lentivirus to constitutively downregulate miR-217. Its regulation on PGC-1α expression was investigated by qRT-PCR and western blot. PGC-1α gene was subsequently downregulated by siRNA in miR-217-downregulated breast cancer cells to examine its effect on cancer proliferation and cell-cycle progression. In addition, another downstream target gene of miR-217, DACH1, was further downregulated in breast cancer cells to investigate the functional association of PGC-1α and DACH1 in miR-217-mediated breast cancer regulation. RESULTS: PGC-1α gene was directly bound by human miR-217. Downregulation of miR-217 in MCF-7 and MDA-MB-231 cells increased PGC-1α production at both mRNA and protein levels. SiRNA-mediated PGC-1α downregulation reversed the inhibition of miR-217-downregulaiton on breast cancer proliferation and cell-cycle progression. Moreover, siRNA-mediated DACH1 downregulation further reversed miR-217-downregulaiton induced inhibition on cancer proliferation and cell-cycle progression in PGC-1α downregulated MCF-7 and MDA-MB-231 cells. CONCLUSION: MiR-217 is the upstream regulator of PGC-1α in breast cancer regulation in vitro, possibly independent of DACH1 signaling pathway.

Optical watermarking based on single-shot-ptychography encoding.

A novel optical encoding method based on single-shot ptychography is proposed for the application of optical watermarking. For the inherent properties of single-shot ptychography, the watermark is encoded into a series of tiny diffraction spots just in one exposure. Those tiny spots have high imperceptibility and compressibility, which are quite suitable for the optical watermarking application. The security of the proposed watermarking is mainly supported by the strong imperceptibility, as well as the introduction of compression encoding and scrambling encoding. In addition, the diversity of the multi-pinhole array and the structural parameters can also be served as security keys. Both numerical simulation and optical experiment demonstrate the high security and the easy implementation of the single-shot-ptychography-based optical watermarking. Further, the compression encoding can largely improve the embedding capacity that enables the multiple-watermarking for more transmitted information and higher security.

Clerodane-type diterpenoids from tuberous roots of Tinospora sagittata (Oliv.) Gagnep.

Three new clerodane type diterpenoids (2-4), together with one known analogues (1), were isolated from the tuberous roots of Tinospora sagittata (Oliv.) Gagnep. Compound 3 is an unusual clerodane diterpenoid with the carbonyl functionality at C-3, which represents the first example from this diterpenoid compounds class. The structures were established on the basis of spectroscopic data interpretation. The absolute configuration of 1 was determined for the first time by single-crystal X-ray diffraction analysis with CuKα irradiation. These isolates were evaluated for their cytotoxic activities against five human cancer cell lines and inhibitory activities on LPS-induced NO production in RAW264.7 cells.

Indole diketopiperazines from endophytic Chaetomium sp 88194 induce breast cancer cell apoptotic death.

Diketopiperazines are important secondary metabolites of the fungi with variety bioactivities. Several species belonging to genus Chaetomium produce compounds of this class, such as chetomin. To identify new antitumor agents, secondary metabolites of fungus Chaetomium sp 88194 were investigated and three new indole diketopiperazines, Chaetocochins G (1), Oidioperazines E (2) and Chetoseminudin E (3), along with two known compounds Chetoseminudins C (4) and N-acetyl-ß-oxotryptamine (5), were obtained. Chaetocochins G and Chetoseminudin E were recrystallized in CHCl3 containing a small amount of MeOH, and their structures with absolute configuration were established by spectroscopic data interpretation and single-crystal X-ray diffraction analysis. The absolute configuration of Oidioperazines E was defined by comparing of experimental and calculated electronic circular dichroism spectra. These isolates were also evaluated the anticancer activity, and Chaetocochins G displayed more potent cytotoxicity in MCF-7 cells than the common chemotherapeutic agent (5-fluorouracil) associated with G2/M cell cycle arrest. More importantly, Chaetocochins G induced cell apoptotic death via caspase-3 induction and proteolytic cleavage of poly (ADP-ribose) polymerase, concomitantly with increased Bax and decreased Bcl-2 expression. Our findings suggested that indole diketopiperazines from endophytic Chaetomium sp 88194 may be potential resource for developing anti-cancer reagents.

Two new secondary metabolites from Xylaria sp. cfcc 87468.

A new isocoumarin glycoside, 3R-(+)-5-O-[6'-O-acetyl]-α-D-glucopyranosyl-5-hydroxymellein (1), and a new phenylethanol glycoside, (-)-phenylethyl-8-O-α-L-rhamno-pyranoside (2), were isolated from the ethyl acetate extract of the fungus Xylaria sp. cfcc 87468, together with five known steroids, ß-sitosterol (3), stigmast-4-en-3-one (4), ergosterol (5), (22E)-cholesta-4,6,8(14),22-tetraen-3-one (6), and 4α-methyl- ergosta-8(14),24(28)-dien-3ß-ol (7). The structures of compounds 1 and 2 were elucidated by MS, extensive 1D and 2D NMR spectroscopy, and the circular dichroism (CD) spectroscopy.

MicroRNA-214 provokes cardiac hypertrophy via repression of EZH2.

Micro RNAs are small, non-coding RNA molecules that regulate gene expression via either translational inhibition or mRNA degredation. Enhancer of zeste homolog 2 (EZH2)-mediated hypertrophic signaling is a major regulatory response to hypertrophic stimuli. In this study, we constructed AAC rat models and PE-induced hypertrophic cardiomyocytes. We demonstrated that miR-214 relative levels were upregulated, whereas EZH2 was downregulated in both vivo and vitro models. Further, one conserved base-pairing site in the EZH2 3'-untranslated region (UTR) was verified. Mutation of the site in the EZH2 3'-UTR completely blocked the negative effect of miR-214 on EZH2, suggesting that EZH2 is a direct target for miR-214 regulation. Using a gain-of-function approach, incorporating the lentivirus constructed miR-214 and its sponge, we demonstrated that miR-214 significantly regulated endogenous levels of EZH2 gene expression; whereas, changes in the expression of the Sine oculis homeobox homolog gene were induced by an adrenergic receptor agonist in the AAC rat model. Having made this study it is possible to conclude that the negative regulation of EZH2 expression contributed to miR-214-mediated cardiac hypertrophy.