[Prediction of quality markers of Angong Niuhuang Pills based on LC-MS and pull-down with SPR chips].

Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 µmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.

Artificial intelligence applied in cardiovascular disease: a bibliometric and visual analysis.

Background: With the rapid development of technology, artificial intelligence (AI) has been widely used in the diagnosis and prognosis prediction of a variety of diseases, including cardiovascular disease. Facts have proved that AI has broad application prospects in rapid and accurate diagnosis. Objective: This study mainly summarizes the research on the application of AI in the field of cardiovascular disease through bibliometric analysis and explores possible future research hotpots. Methods: The articles and reviews regarding application of AI in cardiovascular disease between 2000 and 2023 were selected from Web of Science Core Collection on 30 December 2023. Microsoft Excel 2019 was applied to analyze the targeted variables. VOSviewer (version 1.6.16), Citespace (version 6.2.R2), and a widely used online bibliometric platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references, and keywords in this field. Results: A total of 4,611 articles were selected in this study. AI-related research on cardiovascular disease increased exponentially in recent years, of which the USA was the most productive country with 1,360 publications, and had close cooperation with many countries. The most productive institutions and researchers were the Cedar sinai medical center and Acharya, Ur. However, the cooperation among most institutions or researchers was not close even if the high research outputs. Circulation is the journal with the largest number of publications in this field. The most important keywords are "classification", "diagnosis", and "risk". Meanwhile, the current research hotpots were "late gadolinium enhancement" and "carotid ultrasound". Conclusions: AI has broad application prospects in cardiovascular disease, and a growing number of scholars are devoted to AI-related research on cardiovascular disease. Cardiovascular imaging techniques and the selection of appropriate algorithms represent the most extensively studied areas, and a considerable boost in these areas is predicted in the coming years.

Comparative transcriptome analysis and Arabidopsis thaliana overexpression reveal key genes associated with cadmium transport and distribution in root of two Capsicum annuum cultivars.

The molecular mechanisms underlying high and low cadmium (Cd) accumulation in hot pepper cultivars remain unclear. In this study, comparative transcriptome analysis of root between high-Cd (J) and low-Cd (Z) cultivars was conducted under hydroponic cultivation with 0 and 0.4 mg/L Cd, respectively. The results showed that J enhanced the root uptake of Cd by elevating the expression of Nramp5 and counteracting Cd toxicity by increasing the expression of genes, such as NIR1, GLN1, and IAA9. Z reduced Cd accumulation by enhancing the cell wall lignin synthesis genes PAL, COMT, 4CL, LAC, and POD and the Cd transporters ABC, MTP1, and DTX1. Elevated expression of genes related to sulfur metabolism was observed in Z, potentially contributing to its ability to detoxify Cd. To investigate the function of CaCOMT1, an Arabidopsis thaliana overexpression line (OE-CaCOMT1) was constructed. The results revealed that OE-CaCOMT1 drastically increased the lignin content by 38-42% and reduced the translocation of Cd to the aboveground parts by 32%. This study provides comprehensive insights into the mechanisms underlying Cd accumulation in hot pepper cultivars using transcriptome analysis. Moreover, this study elucidates the critical function of CaCOMT1, providing a theoretical foundation for the production of low-Cd vegetables for food safety.

ASCs-EVs Inhibit Apoptosis and Promote Myocardial Function in the Infarcted Heart via miR-221.

BACKGROUND: Extracellular vehicles (EVs) secreted from adipose-derived stem cells (ASCs) (ASCs-EVs) have the potential to treat myocardial infarction (MI), although the underlying mechanism remains unclear. The current study explored the ability of ASCs-EVs to inhibit apoptosis and promote myocardial function in the infarcted heart via microRNAs (miRNAs)-221. METHODS: In hypoxia-induced H9C2 cells, a cardiac cell strain derived from the SD Rat left ventricle, we measured the cell viability and apoptosis-related protein expression after transfection with the ASCs-EVs-NC (negative control for EVs-miR-221) or ASCs-EVs-miR-221 mimics. We then verified the cardioprotective effects of miR-221-overexpressing ASCs-EVs by investigating myocardial cell apoptosis and cardiac function in a MI rat model treated with ASCs-EVs from miR-221-overexpressing ASCs by comparing control with ASC treatment. RESULTS: The in vitro experiment results showed that the proliferation of H9C2 cells and the anti-apoptotic protein expression were significantly enhanced by the ASCs-EVs-miR-221 mimic. The in vivo experiment results found that ASCs-EVs from miR-221-overexpressing ASCs have cardioprotective effects, as demonstrated by lower serum troponin levels and left ventricular end-systolic volume, and a lower number of apoptotic myocardial cells than those in control and ASC-treated rats. CONCLUSIONS: ASCs-EVs have therapeutic effects on MI by inhibiting cardiomyocyte apoptosis via miR-221.

Quality evaluation of compounds in leaves of six Taxus species based on UPLC-MS/MS and chemometrics.

Introduction: Taxus species are used as medicinal plants all over the world. The leaves of Taxus species are sustainable medicinal resources that are rich in taxoids and flavonoids. However, traditional identification methods cannot effectively identify Taxus species on the basis of leaces used as raw medicinal materials, because their appearance and morphological characteristics are almost the same, and the probability of error identification increases in accordance with the subjective consciousness of the experimenter. Moreover, although the leaves of different Taxus species have been widely used, their chemical components are similar and lack systematic comparative research. Such a situation is challenging for quality assessment. Materials and methods: In this study, ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry combined with chemometrics was applied for the simultaneous determination of eight taxoids, four flavanols, five flavonols, two dihydroflavones, and five biflavones in the leaves of six Taxus species, namely, T. mairei, T. chinensis, T. yunnanensis, T. wallichiana, T. cuspidata, and T. media. Chemometric methods, including hierarchical cluster analysis, principal component analysis, orthogonal partial least squares-discriminate analysis, random forest iterative modeling, and fisher linear discriminant analysis, were utilized to differentiate and evaluate the six Taxus species. Results: This proposed method exhibited good linearity (R 2 = 0.9999-0.9972) with a lower quantification limits of 0.94-3.05 ng/mL for all analytes. The intra- and inter-day precisions were within 6.83%. Six compounds, namely, 7-xylosyl-10-deacetyltaxol, ginkgetin, rutin, aromadendrin, 10-deacetyl baccatin III, and epigallocatechin, were identified through chemometrics for the first time. These compounds can be used as important chemical markers to distinguish the above six Taxus species rapidly. Conclusion: This study established a method for determination of the leaves of six Taxus species, and revealing the differences in the chemical components of these six Taxus species.

Content-Aware Unsupervised Deep Homography Estimation and its Extensions.

Homography estimation is a basic image alignment method in many applications. It is usually done by extracting and matching sparse feature points, which are error-prone in low-light and low-texture images. On the other hand, previous deep homography approaches use either synthetic images for supervised learning or aerial images for unsupervised learning, both ignoring the importance of handling depth disparities and moving objects in real-world applications. To overcome these problems, in this work, we propose an unsupervised deep homography method with a new architecture design. In the spirit of the RANSAC procedure in traditional methods, we specifically learn an outlier mask to only select reliable regions for homography estimation. We calculate loss with respect to our learned deep features instead of directly comparing image content as did previously. To achieve the unsupervised training, we also formulate a novel triplet loss customized for our network. We verify our method by conducting comprehensive comparisons on a new dataset that covers a wide range of scenes with varying degrees of difficulties for the task. Experimental results reveal that our method outperforms the state-of-the-art, including deep solutions and feature-based solutions.

Relationship between platelet activation markers and spontaneous abortion: A meta-analysis.

Numerous studies have indicated that mean platelet volume (MPV) and platelet distribution width (PDW) were correlated with spontaneous abortion (SAB), but the results were contradictory. Hence, we performed a meta-analysis to assess the association of MPV and PDW with SAB. We systematically searched on China National Knowledge Internet, PubMed, and Embase up to May 2022 to retrieve eligible studies. The synthesized standard mean difference (SMD) with a 95% confidence interval (CI) was used to evaluate the correlation of MPV and PDW with SAB. A total of 20 studies were finally included in this meta-analysis. The pooled analysis results showed that PDW was markedly increased in patients with SAB versus women with a healthy pregnancy (SMD = 1.03; 95% CI: 0.51-1.54; p = 0.0001), while there were no significant differences in MPV between women with SAB and those with healthy pregnancy (SMD = 0.19; 95% CI: -0.26 to 0.65; p = 0.40). Therefore, PDW may serve as a potential marker for predicting SAB. However, homogeneous and multiethnic studies with larger sample sizes are warranted to validate our findings due to several limitations in this meta-analysis.

Association between IL1RL1 gene polymorphisms and allergic rhinitis risk in the Chinese Han population.

BACKGROUND: Although it has been confirmed that IL1RL1 is involved in the occurrence of allergic rhinitis (AR), the role of IL1RL1 gene single nucleotide polymorphisms (SNPs) in AR is still unclear. METHODS: We performed a case-control study including 1000 AR patients and 1000 healthy controls. The four SNPs rs72823628 G > A, rs950881 G > T, rs72823641 T > A and rs3771175 T > A in IL1RL1 were chosen and genotyped using Agena MassARRAY platform. The relationship between IL1RL1 SNPs and AR risk was analyzed by logistic regression and assessed with odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). RESULTS: Overall analysis revealed that IL1RL1 gene rs72823628, rs950881 and rs3771175 were associated with a reduced AR risk. Stratified analysis showed that the three SNPs (rs72823628, rs950881 and rs3771175) were obviously linked to a reduced risk of AR in males. Moreover, no correlation was observed between haplotypes and reduced AR risk after the false discovery rate (FDR) correction. The false positive report probability (FPRP) analysis was used to further validate significant findings. CONCLUSION: Our study is the first to indicate that IL1RL1 gene polymorphisms (rs72823628, rs950881 and rs3771175) may be correlated with decreased risk of AR in the Chinese Han population.

Biomarkers of joint metabolism and bone mineral density are associated with early knee osteoarthritis in premenopausal females.

INTRODUCTION: Biomarkers of bone and cartilage metabolism were proposed as early diagnosis indicators for knee osteoarthritis (OA), however, which were influenced by disease stage, age, and menopause state. Accurate diagnosis indicators are eagerly awaited. The current study aims to investigate associations of joint metabolism biomarkers and bone mineral density (BMD) with early knee OA in males and premenopausal females before age 50 years. METHOD: A total of 189 patients aged before 50 years with early knee OA and 152 healthy participants were enrolled. Levels of bone biomarkers (PINP, OC, and CTX-I) and cartilage biomarkers (PIIANP, COMP, CTX-II, and MMP-3) were assessed. BMD was measured at the lumbar, femoral neck, and hip. Multivariate regression analyses were performed to evaluate the relationship between biomarkers, BMD, and early knee OA. RESULTS: Serum COMP, urine CTX-II and BMD at femoral neck and hip were increased in premenopausal patients as compared to control; with serum PINP and OC reduced. Meanwhile, serum COMP, urine CTX-II, and BMD at femoral neck and hip showed positive associations with premenopausal early knee OA, while serum PINP had negative association. However, in male patients, only serum COMP was higher than control, and no association of biomarkers or BMD was found with early knee OA. CONCLUSIONS: The joint metabolism biomarkers and BMD showed multiple associations with early knee OA in premenopausal females, but not in males aged before 50 years. It was suggested that sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA. Key Points • The joint metabolism biomarkers and BMD are associated with early knee OA in premenopausal females, but not in males aged before 50 years. • Sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA.

Cartilage oligomeric matrix protein affects the biological behavior of papillary thyroid carcinoma cells by activating the PI3K/AKT/Bcl-2 pathway.

Objective: To explore the effect of cartilage oligomeric matrix protein (COMP) on papillary thyroid carcinoma (PTC). Methods: COMP expression levels in PTC tissues and matched adjacent normal tissues were measured using tissue microarrays. Human PTC cells were cultured and transduced with lentiviral short hairpin RNA against COMP (COMP-shRNA), a negative control (NC) shRNA, or mock transfected (Control). We used the Cell Counting Kit-8, performed colony formation assays, wound healing assays, Transwell invasion assays, flow cytometry, and measured the expression of apoptosis-related proteins at the mRNA and protein levels to explore the effects of COMP on the biological behavior of PTC cells and to discover the specific signaling pathway involved in these processes. Results: COMP expression was significantly higher in PTC tissues than in adjacent normal tissues. At the cellular level, COMP promoted cell migration, increased the invasiveness of PTC cells, and inhibited apoptosis. However, differences in cell proliferation were only observed within 72 hours. At the same time, colony formation assays showed that silencing COMP inhibited the proliferation of PTC cells. We also found that COMP regulated the behavior of PTC cells by activating the PI3K/AKT/Bcl-2 pathway. Conclusions: COMP is upregulated in PTC, which enhances cancer cell invasion and inhibits apoptosis, contributing to the development and progression of PTC. Thus, COMP may serve as a new biomarker for PTC.

Exploring the Role of SRC in Extraocular Muscle Fibrosis of the Graves' Ophthalmopathy.

The Graves' disease is an autoimmune disease highly associated with thyroid cancer. The Graves' ophthalmopathy (GO) is a special Graves' disease with inflammatory ophthalmopathy being a typical extrathymic complication. GO is caused by the formation of orbital fat and extraocular muscle fibrosis due to the inflammation of orbital connective tissues. Thus, controlling extraocular muscle fibrosis is critical for the prognosis of GO. The objective of this study is to identify and experimentally validate key genes associated with GO and explore their potential function mechanisms especially on extraocular muscle fibrosis. Specifically, we first created a GO mouse model, and performed RNA sequencing on the extraocular muscles of fibrotic GO mice and controls. SRC was identified as the most significant unstudied differentially expressed gene between GO mice and controls. Thus, we conducted a few in vitro analyses to explore the roles and functions of SRC in GO, for which we selected primary cultured orbital fibroblast (OF) as the in vitro cell line model. It is known that myofibroblast (MFB), which expresses α-SMA, is an important target cell in the process of fibrosis. Our experiment suggests that TGF-ß can induce the transformation from OF to MFB, however, the transformation was inhibited by silencing the SRC gene in OF. In addition, we also inhibited TGF-ß/Smad, NF-κB, and PI3K/Akt signaling pathways to analyze the interaction between these pathways and SRC. In conclusion, the silence of SRC in OF can inhibit the transformation from OF to MFB, which might be associated with the interaction between SRC and a few pathways such as TGF-ß/Smad, NF-κB, and PI3K/Akt.

Squamous cell carcinoma antigen, platelet distribution width, and prealbumin collectively as a marker of squamous cell cervical carcinoma.

BACKGROUND: Squamous cell cervical carcinoma is the most common gynecological malignant disorder worldwide. Early detection of squamous cell cervical carcinoma is needed for proper clinical management. Squamous cell carcinoma antigen (SCCA) is commonly used as a tumor marker for squamous cell cervical carcinoma. Platelet distribution width (PDW) is an indicator of platelet activation. Prealbumin is a negative acute-phase protein. OBJECTIVE: The aim of this study was to investigate the ability of SCCA, PDW, and prealbumin individually or in combination, to distinguish between cervical carcinoma and control subjects. MEHTODS: Two hundred and twenty patients with squamous cell cervical carcinoma and 211 control subjects were included in the study. Patients' characteristics and hematologic tests data at initial diagnosis were collected. RESULTS: Our results showed that SCCA and PDW were higher, and prealbumin was lower in cervical carcinoma patients than in control subjects. Single biomarker had AUC value ranging from 0.753 for SCCA to 0.845 for PDW. The combination of SCCA and PDW increased the AUC to 0.900 (p< 0.0001). In addition, the combination of SCCA, PDW and prealbumin exhibited a significantly larger AUC of 0.917 (0.887-0.942), significantly higher than those of any single marker. CONCLUSIONS: The combined use of SCCA, PDW and prealbumin can accurately distinguish squamous cell cervical carcinoma from control subjects. This promising approach could be helpful in early detection of squamous cell cervical carcinoma.

Giant Serpentine Middle Cerebral Artery Aneurysm.

Giant serpentine aneurysms are rare entity, which have unique presentations and distinct angiographic features, with poor prognosis if not treated. In this paper, a patient with a giant serpentine aneurysm originated from right middle cerebral artery was reported. A 38-year-old woman suffered from progressively headache and vision declined. The computed tomography and magnetic resonance image revealed a partially calcified, large mass (approximately 80 × 70 × 60 mm sized) in the right frontal-temple lobe. On computed tomography angiography, an unruptured, giant, partially thrombosed, serpentine aneurysm was confirmed. After treatment by craniotomy, the patient was rehabilitation. Operation is an effective method for the treatment of giant serpentine aneurysms. In addition, cerebral angiography and balloon test occlusion are the crucial way of preoperative assessment.

Intrathecal injection of tigecycline in treatment of multidrug-resistant Acinetobacter baumannii meningitis: a case report.

The ubiquitous Acinetobacter baumannii is an important and troublesome pathogen of nosocomial infection. Multidrug-resistant A baumannii meningitis is very difficult to treat, usually with high mortality. The disease is generally associated with craniotomy, but rarely with lumbar puncture. However, in our case, a 45-year-old male construction worker suffered multidrug-resistant A baumannii meningitis associated with lumbar puncture. The patient responded poorly to the initial treatment with an intravenous infusion of tigecycline. However, later treatment with an intrathecal injection of tigecycline (concentration 1 mg/mL) at a dose of 10 mg every 12 hours proved to be highly efficacious. Thus, intrathecal injection of tigecycline should be seriously considered as a treatment for multidrug-resistant A baumannii meningitis.

Gallstone disease is associated with arterial stiffness progression.

Gallstones have been linked to dyslipidemia, metabolic syndrome and cardiovascular disease. Arterial stiffness is an indicator of subclinical atherosclerosis. The aim of this study was to prospectively examine the relationship between gallstone disease and arterial stiffness progression in 347 men and 454 women. These subjects were followed for 7 years. Arterial stiffness progression was measured based on increases in brachial-ankle pulse wave velocity. Changes in brachial-ankle pulse wave velocity during the study period were significantly greater in patients with gallstones than in subjects without gallstones. After adjusting for multiple risk factors, gallstone disease was found to be a significant and independent predictor of brachial-ankle pulse wave velocity progression (ß=0.189; P<0.001). In conclusion, gallstone disease is an independent predictor of arterial stiffness progression, even after adjusting for other cardiovascular risk factors.

Reduced prealbumin is associated with bone mineral density in women with osteoporosis.

OBJECTIVES: Poor nutritional status is associated with osteoporosis (OP) in postmenopausal women. Moreover, recent studies documented that prealbumin is the best and most widely used parameter to monitor nutrition intervention and is a sensitive predictor of short-term outcome compared with albumin. Therefore, the aim of this study was to examine the association of prealbumin levels with bone mineral density (BMD) in patients with OP. METHODS: This cross-sectional study recruited 664 women. Prealbumin levels and BMD at femoral neck and lumbar spine were measured. Multiple linear regression analysis was performed to assess the correlation between prealbumin and BMD. RESULTS: Results of this study found that prealbumin levels dropped gradually as BMD decreased. Furthermore, partial correlation analysis revealed that prealbumin was correlated with BMD after adjusting for confounders. Multiple linear regression analysis showed that prealbumin is a significant factor for reduced BMD in women (for BMD at spine L2-4, ß = 0.186, P < 0.001; for BMD at femoral neck, ß = 0.180, P < 0.001). CONCLUSION: Prealbumin was significantly correlated with BMD after adjusting for traditional cardiovascular risk factors. Further prospective research is warranted to further enhance our understanding of the important role of prealbumin in OP.

Targeting proprotein convertases in furin-rich lung cancer cells results in decreased in vitro and in vivo growth.

Proprotein convertases (PCs) are serine proteases with an active role in the post-translational processing of numerous inactive proteins to active proteins including many substrates of paramount importance in cancer development and progression. Furin (PCSKC3), a well-studied member of this family, is overexpressed in numerous human and experimental malignancies. In the present communication, we treated two furin-overexpressing non-small cell carcinoma (NSCLC) cell lines (Calu-6 and HOP-62) with the PC inhibitor CMK (Decanoyl-Arg-Val-Lys-Arg-chloromethylketone). This resulted in a diminished IGF-1R processing and a simultaneous decrease in cell proliferation of two NSCLC lines. Similarly, growth of subcutaneous xenografts of both cell lines, were partially inhibited by an in vivo treatment with the same drug. These observations point to a potential role of PC inhibitors in cancer therapy. © 2016 Wiley Periodicals, Inc.

Bone mineral density is associated with left ventricular diastolic function in women.

BACKGROUND: Low bone mineral density (BMD) and left ventricular (LV) diastolic function are associated with heart failure. However, little is known about the association between BMD and LV diastolic function. HYPOTHESIS: BMD is independently related to LV diastolic function in women. METHODS: We conducted a cross-sectional study of 432 women. Brachial-ankle pulse wave velocity (baPWV) and BMD measurements were performed. LV diastolic function and structure were assessed by echocardiographic examination. RESULTS: BaPWV and the percentage of LV diastolic dysfunction increased with progressive bone loss. Moreover, partial correlation analysis demonstrated that BMD at spine L2-4 and at femoral neck were correlated with baPWV and LV diastolic function parameters after adjusting covariates. Multivariate logistic regression analysis revealed that osteoporosis was independently associated with LV diastolic dysfunction in women. CONCLUSIONS: Osteoporosis is independently associated with LV diastolic dysfunction in women. A prospective study is needed to elucidate the effects of BMD on cardiac function in women.

Adenosine analogs as inhibitors of tyrosyl-tRNA synthetase: Design, synthesis and antibacterial evaluation.

Herein we describe the synthesis and evaluation of a series of adenosine analogs for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Out of these compounds, compound c6 has much stronger antibacterial potency against Pseudomonas aeruginosa than ciprofloxacin, and was determined to target tyrosyl-tRNA synthetase with IC50 of 0.8±0.07 µM. Structure-activity relationship analysis suggested that introduction of a fluorine atom at the 3'-position of benzene ring of the phenylacetyl moiety significantly increased affinities to the enzyme. In comparison with isopropylidene analogs, 2',3'-deprotected compounds displayed higher inhibitory activity. Molecular dockings provided an explanation for observations in biological assays.