Development of an optimized RPA-PfAgo detection system for MTHFR C677T polymorphism genotyping.

This study introduces an efficient RPA-PfAgo detection system for the MTHFR C677T polymorphism, proposing a potential strategy to simplify the genotyping process. By optimizing recombinase polymerase amplification (RPA) with Pyrococcus furiosus Argonaute (PfAgo) nucleases, we achieved DNA amplification at a constant temperature. The assay was fine-tuned through meticulous primer and guide DNA selection, with optimal conditions established at 2.0 µL of MgAc, a reaction temperature of 42 °C, and a 10-minute reaction time for RPA. Further optimization of the PfAgo cleavage assay revealed the ideal concentrations of MnCl2, guide DNA, molecular beacon probes, the PfAgo enzyme, and the RPA product to maximize sensitivity and specificity. Clinical validation of 20 samples showed 100% concordance with Sanger sequencing, confirming the method's precision. The RPA-PfAgo system is a promising tool for on-site genotyping, with broad applications in personalized medicine and disease prevention.

Unveiling the neuroprotective properties of isoflavones: current evidence, molecular mechanisms and future perspectives.

Neurodegenerative diseases encompass a wide range of debilitating and incurable brain disorders characterized by the progressive deterioration of the nervous system's structure and function. Isoflavones, which are naturally occurring polyphenolic phytochemicals, have been found to regulate various cellular signaling pathways associated with the nervous system. The main objective of this comprehensive review is to explore the neuroprotective effects of isoflavones, elucidate the underlying mechanisms, and assess their potential for treating neurodegenerative disorders. Relevant data regarding isoflavones and their impact on neurodegenerative diseases were gathered from multiple library databases and electronic sources, including PubMed, Google Scholar, Web of Science, and Science Direct. Numerous isoflavones, including genistein, daidzein, biochanin A, and formononetin, have exhibited potent neuroprotective properties against various neurodegenerative diseases. These compounds have been found to modulate neurotransmitters, which in turn contributes to their ability to protect against neurodegeneration. Both in vitro and in vivo experimental studies have provided evidence of their neuroprotection mechanisms, which involve interactions with estrogenic receptors, antioxidant effects, anti-inflammatory properties, anti-apoptotic activity, and modulation of neural plasticity. This review aims to provide current insights into the neuroprotective characteristics of isoflavones and shed light on their potential therapeutic applications in future clinical scenarios.

Multimodal echocardiography for assessing whether left ventricular geometry affects right atrial phasic function in patients with obstructive sleep apnea syndrome: A cross-sectional observational study.

BACKGROUND: Recent studies have shown that right atrial (RA) function are important predictors of cardiovascular morbidity and mortality. However, the study data about RA phasic function in obstructive sleep apnea syndrome (OSAS) patients are scarce, especially based on the left ventricular geometry. So, we aimed to assess the influence of left ventricular geometry on RA phasic function in OSAS patients via a multimodal echocardiographic approach. METHODS: Total of 235 OSAS patients were enrolled in this cross-section study and underwent complete clinical, polysomnography, and echocardiography examinations. The OSAS patients were divided into four groups based on left ventricular mass index (LVMI) and relative wall thickness (RWT): normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). RA phasic function was evaluated via multimodal echocardiography approach (two-dimensional echocardiography biplane method [2DE]; two-dimensional speckle-tracking echocardiography [2D-STE]; and three-dimensional echocardiography [3DE]). The multiple linear regression analysis was used to determine the relationship between left ventricular geometry and RA phasic function. RESULTS: The RA volume and indices increased from NG to CR to EH to CH. RA total emptying fraction and RA strain during systole decreased from NG to CR to EH to CH. RA passive emptying fraction and RA strain during early diastole similarly decreased. RA active emptying fraction and RA strain during late diastole also gradually increased similarly. In analyses that adjusted for gender, age, body mass index, systolic blood pressure, apnea-hypopnea index, LVMI, systolic pulmonary artery pressure, and right ventricular free wall thickness, CH was associated with RA reservoir and conduit function via 2DE area-length method, whereas CH and EH were associated with RA reservoir and conduit function via 2D-STE and 3DE method. Further, CH was associated with RA booster pump function via 2DE area-length method, 2D-STE, and 3DE method. CONCLUSION: The RA volumes and phasic function varied with left ventricular geometry via multimodal echocardiography approach. CH had the apparent negative effect on RA phasic function.

Ononin triggers ferroptosis-mediated disruption in the triple negative breast cancer both in vitro and in vivo.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is difficult to treat due to a lack of targeted therapies. In this study, we aimed to investigate whether a natural flavonoid compound called ononin could be effective in treating TNBC by triggering ferroptosis in MDA-MB-231 and 4 T1 cell lines, and MDA-MB-231-xenograft nude mice model. Ononin inhibited TNBC through ferroptosis, which was determined by MTT assay, flow cytometry, RT-PCR, immunofluorescence, transmission electron microscopy, histological analysis, western blot and bioluminescence assay. Our results showed that treatment with ononin led to increased levels of malondialdehyde and reactive oxygen species and decreased activity of superoxide dismutase, which are indicatives of ferroptosis. We also found that ononin downregulated two key markers of ferroptosis, SLC7A11 and Nrf2, at both the transcriptional and translational level. Additionally, the administration of ononin resulted in a notable decrease in tumor size and weight in the mouse model. Furthermore, it was observed to enhance the rate of apoptosis in TNBC cells. Importantly, ononin did not induce any histological changes in the kidney, liver, and heart. Taken together, our findings suggest that ononin could be a promising therapeutic strategy for TNBC, and that it works by disrupting the Nrf2/SLC7A11 axis through ferroptosis. These results are encouraging and may lead to the development of new treatments for this challenging cancer subtype.

Association of the TNF-α-308G>A gene polymorphism with left ventricular geometry and functional abnormalities in obstructive sleep apnea subjects.

OBJECTIVE: Tumor necrosis factor-α (TNF-α) can induce left ventricular remodeling. In this study, we investigated whether the TNF-α-308G>A polymorphism is associated with left ventricular geometry (LVG) and left ventricular functional abnormalities in obstructive sleep apnea (OSA) subjects. METHODS: Two hundred and seventy-eight subjects were enrolled. Echocardiography and genetic data were assessed in all patients. Geometric patterns of the left ventricle were determined from the relative wall thickness and left ventricular mass index (LVMI). Genetic analysis for the TNF-α-308G>A SNP rs1800629 was identified by Sanger sequencing. The correlations of the TNF-α-308G>A polymorphism with LVG and left ventricular function were analyzed by difference analysis and logistic regression. RESULTS: The chi-square test showed that there were differences in genotype distributions among the four groups (p = 0.033), such that the frequency of GA+AA genotypes was significantly higher in the concentric hypertrophy group than in the normal geometry group (p < 0.05). Independent sample T tests showed that the GA+AA genotypes had higher IVST, LVPWT, LVMI, E/e' values, and lower e' values than those of the GG genotype (p < 0.05). Logistic regression analysis showed that the TNF-α-308G>A polymorphism was independently correlated with eccentric hypertrophy (OR = 2.456, p = 0.047) and concentric hypertrophy (OR = 2.456, p = 0.047). CONCLUSION: In OSA patients, the TNF-α-308G>A polymorphism was linked to LVG and abnormal left ventricular diastolic function, suggesting that the TNF-α-308G>A polymorphism may have an important influence on LVG alterations.

Danggui Buxue Tang improves therapeutic efficacy of doxorubicin in triple negative breast cancer via ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Tang (DBT) has been used for over 800 years to enhance Qi and nourish Blood, and it is particularly beneficial for cancer patients. Recent research has shown that combining DBT with chemotherapy agents leads to superior anti-cancer effects, thereby enhancing therapeutic efficacy. AIM OF THE STUDY: The aim of this study was to evaluate the effectiveness of a combination therapy involving doxorubicin (DOX) and Danggui Buxue Tang (DBT) in the treatment of triple-negative breast cancer (TNBC) and to elucidate the underlying mechanisms of action. MATERIALS AND METHODS: In vitro experiments were performed using MDA-MB-231 and 4T1 cells, while in vivo experiments were carried out using MDA-MB-231 xenograft mice. The therapeutic effects of the combination therapy were evaluated using various techniques, including MTT assay, colony formation assay, flow cytometry, transwell assay, immunofluorescence, transmission electron microscopy (TEM), histological analysis, western blotting, and bioluminescence assay. RESULTS: DBT was found to enhance DOX's anti-TNBC activity in vitro by promoting ferroptosis, as evidenced by the observed mitochondrial morphological changes using TEM. The combination therapy was also found to reduce the expression of Nrf2, HO-1, and GPX4, which are all targets for ferroptosis induction, while simultaneously increasing ROS production. Additionally, the combination therapy reduced nuclear accumulation and constitutive activation of Nrf2, which is a significant cause of chemotherapy resistance and promotes cancer growth. In vivo experiments using an MDA-MB-231 xenograft animal model revealed that the combination therapy significantly reduced tumor cell proliferation and accelerated TNBC deaths by modulating the Nrf2/HO-1/GPX4 axis, with no evidence of tissue abnormalities. Moreover, the combination therapy exhibited a liver protective effect, and administration of Fer-1 was able to reduce the ROS formation produced by the DBT + DOX combination therapy. CONCLUSION: This study provides evidence that the combination therapy of DOX and DBT has the potential to treat TNBC by promoting ferroptosis through the Nrf2/HO-1/GPX4 axis.

A novel FCTF evaluation and prediction model for food efficacy based on association rule mining.

Introduction: Food-components-target-function (FCTF) is an evaluation and prediction model based on association rule mining (ARM) and network interaction analysis, which is an innovative exploration of interdisciplinary integration in the food field. Methods: Using the components as the basis, the targets and functions are comprehensively explored in various databases and platforms under the guidance of the ARM concept. The focused active components, key targets and preferred efficacy are then analyzed by different interaction calculations. The FCTF model is particularly suitable for preliminary studies of medicinal plants in remote and poor areas. Results: The FCTF model of the local medicinal food Laoxianghuang focuses on the efficacy of digestive system cancers and neurological diseases, with key targets ACE, PTGS2, CYP2C19 and corresponding active components citronellal, trans-nerolidol, linalool, geraniol, α-terpineol, cadinene and α-pinene. Discussion: Centuries of traditional experience point to the efficacy of Laoxianghuang in alleviating digestive disorders, and our established FCTF model of Laoxianghuang not only demonstrates this but also extends to its possible adjunctive efficacy in neurological diseases, which deserves later exploration. The FCTF model is based on the main line of components to target and efficacy and optimizes the research level from different dimensions and aspects of interaction analysis, hoping to make some contribution to the future development of the food discipline.

Utilization of the GOAL questionnaire as a standardized screening tool for obstructive sleep apnea.

The purpose of our study was to evaluate the application value of the GOAL questionnaire in screening obstructive sleep apnea (OSA) and to compare it with the other three questionnaires in sleep clinics. A cross-sectional study was conducted in 436 patients who had undergone nocturnal polysomnography in the sleep unit of the First Hospital of Shanxi Medical University between September 2021 and May 2022, and all patients completed the four questionnaires (GOAL questionnaire, STOP-Bang questionnaire, NoSAS score and No-Apnea score) truthfully, and the patients were divided into 3 groups: AHI ≥ 5 events/h group, AHI ≥ 15 events/h group and AHI ≥ 30 events/h group. The predictive effect of the questionnaire on different AHI cut-off values was calculated, and performance of four questionnaires was assessed by the discriminatory ability. This study ultimately included 410 patients, and there were statistically significant differences in gender, age, BMI, neck circumference, clinical symptoms, hypertension, diabetes, AHI, and minimum oxygen saturation between OSA and non-OSA groups (P < 0.05). The AUC for No-Apnea score was 0.79, the AUC for STOP-Bang questionnaire was 0.86, the AUC for NoSAS score was 0.81, and the AUC for GOAL questionnaire was 0.77. These four questionnaires were effective in screening OSA when AHI ≥ 15 events/h. Similar to No-Apnea score, STOP-Bang score and NoSAS score, GOAL questionnaire has a good predictive value for OSA, which is a questionnaire suitable for primary health-care centers and clinics.

Danggui Buxue Tang: A Review of its Major Components.

Context: Danggui Buxue Tang (DBT) is a classical Chinese medicine that practitioners have used for thousands of years. Historically, those practitioners have used 16 prescriptions of DBT but currently are using only three prescriptions. Objective: The review intended to summarize pharmacological profiles of DBT and also clarify the major active chemicals found within it to provide a better understanding of the significance of DBT clinically. Design: The research team performed a narrative review by searching Pubmed databases. The search used the keywords Danggui Buxue Tang, bioactive chemcials, pharmacological functions. Setting: The databases setting were done by Gong Guowei and Zhou Xuan in the Zunyi Medical University, Zhuhai campus. Results: There are multiple results related to the crude fractions isolated from Danggui Buxue Tang, and also included the clinical trails. Conclusions: Thousands of years of clinical experience have ensured the efficacy of TCM treatments, which can determine the direction of basic research. That research can modify formulas at the molecular level to improve targeting and specificity in the treatment of specific diseases. As a result, the discovery and identification of new compounds within the herbal complex can provide useful research ideas and ensure the viability of new drug development.

Serum uric acid is related to left ventricular geometry and function in patients with obstructive sleep apnea.

INTRODUCTION: Serum uric acid (SUA) is an oxidative stress-related biomarker of cardiovascular risk. We sought to discover whether or not SUA was related to left ventricular geometry (LVG) and function among individuals with obstructive sleep apnea (OSA). METHODS: Patients with OSA and healthy controls were assessed for clinical features, echocardiography, polysomnography, and blood biochemical data. Patients with OSA were divided into four groups: normal geometry (NG), concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH). Correlations of SUA with left ventricular (LV) structure and function were examined through Pearson correlation analysis. The risk variables of LVG were investigated using a multivariate logistic regression model. RESULTS: Compared to controls, patients with OSA had greater SUA levels. The eccentric hypertrophy (EH) and concentric hypertrophy (CH) groups showed substantially greater SUA levels than the normal geometry (NG) and concentric remodeling (CR) groups (p < 0.05). SUA correlated positively with left ventricular mass index (LVMI) and relative wall thickness (RWT) but negatively with the E/A ratio, according to the Pearson correlation analysis. SUA independently affected EH (OR = 1.021, 95%CI = 1.015-1.028, p < 0.001) and CH (OR = 1.034, 95%CI = 1.025-1.043, p < 0.001) in patients with OSA by the multivariate logistic regression model. CONCLUSIONS: Patients with OSA had elevated levels of SUA, which were seen to be closely linked with abnormal LVG and function. The findings suggest that SUA may raise the risk of LV structural and functional impairment in patients with OSA.

Zearalenone lactonase: characteristics, modification, and application.

Zearalenone (ZEN) and its derivatives are one of the most contaminated fungal toxins worldwide, posing a severe threat to food security and human life. Traditional physical and chemical detoxifying methods are unsatisfactory due to incomplete detoxification, nutrient loss, and secondary pollutants. In recent years, bioremediation for eliminating fungal toxins has been gradually investigated. ZEN lactone hydrolase (lactonase) has been widely studied because of its high activity, mild conditions, and non-toxic product property. This review comprehensively represents the gene mining, characterization, molecular modification, and application of microbial-derived ZEN lactonases. It is aimed to elucidate the advantages and challenges of ZEN lactonases in industrial application, which also provides perspectives on obtaining innovative and promising biocatalysts for ZEN degradation. KEY POINTS: • A timely and concise review related to enzymatic elimination towards ZEN is shown. • The catalytic conditions and mechanism of ZEN lactonase is presented. • The modification and application of ZEN lactonase are exhibited also.

Model Embraced Electromechanical Coupling Time for Estimation of Heart Failure in Patients With Hypertrophic Cardiomyopathy.

Objective: This study aimed to establish a model embraced electromechanical coupling time (EMC-T) and assess the value of the model for the prediction of heart failure (HF) in patients with hypertrophic cardiomyopathy (HCM). Materials and Methods: Data on 82 patients with HCM at Shaanxi Provincial People's Hospital between February 2019 and November 2021 were collected and then formed the training dataset (n = 82). Data were used to screen predictors of HF using univariate and multivariate analyses. Predictors were implemented to discover the optimal cut-off value, were incorporated into a model, and shown as a nomogram. The cumulative HF curve was calculated using the Kaplan-Meier method. Additionally, patients with HCM at other hospitals collected from March 2019 to March 2021 formed the validation dataset. The model's performance was confirmed both in training and validation sets. Results: During a median of 22.91 months, 19 (13.38%) patients experienced HF. Cox analysis showed that EMC-T courses in the lateral wall, myoglobin, PR interval, and left atrial volume index were independent predictors of HF in patients with HCM. Five factors were incorporated into the model and shown as a nomogram. Stratification of patients into two risk subgroups by applying risk score (<230.65, ≥230.65) allowed significant distinction between Kaplan-Meier curves for cumulative incidence of HF events. In training dataset, the model had an AUC of 0.948 (95% CI: 0.885-1.000, p < 0.001) and achieved a good C-index of 0.918 (95% CI: 0.867-0.969). In validation dataset, the model had an AUC of 0.991 (95% CI: 0.848-1.000, p < 0.001) and achieved a strong C-index of 0.941 (95% CI: 0.923-1.000). Calibration plots showed high agreement between predicted and observed outcomes in both two datasets. Conclusion: We established and validated a novel model incorporating electromechanical coupling time courses for predicting HF in patients with HCM.

The relationship of interleukin-6 and C-reactive protein with left ventricular geometry and function in patients with obstructive sleep apnea syndrome and pre-hypertension.

OBJECTIVE: To assess the relationship of interleukin-6 (IL-6) and C-reactive protein (CRP) levels with left ventricular geometry (LVG) and function in patients with obstructive sleep apnea syndrome (OSAS) and pre-hypertension. METHODS: A total of 458 patients were assigned into four groups: normal geometry (NG), concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH). Pearson correlation and multivariate logistic regression analyses were used to determine the correlation between IL-6, CRP, and clinical, polysomnographic, and biochemical parameters with LVG and function. RESULTS: IL-6 and CRP levels were higher in the EH and CH groups than those in the NG and CR groups. The results of the Pearson correlation analysis showed that IL-6 level was positively correlated with the E/e' ratio and peak systolic pulmonary venous reverse velocity (PVa) duration time (PVaD), while negatively correlated with the E/A ratio, s', and left ventricular ejection fraction (LVEF). CRP level was positively correlated with A-wave duration time (AD), peak systolic pulmonary venous flow velocity (PVs), PVa and PVaD, while negatively correlated with the E/A ratio. The results of the multivariate logistic regression analysis revealed that IL-6 and CRP levels were correlated with EH (ß = 1.213, odds ratio [OR] = 3.363, p < 0.001; ß = 1.258, OR = 3.518, p < 0.001) and CH (ß = .938, OR = 2.555, p = 0.008; ß = 1.239, OR = 3.454, p < 0.001). CONCLUSION: IL-6 and CRP levels are associated with LVG and function, suggesting that IL-6 and CRP levels are involved in OSAS and pre-hypertension, leading to abnormal left ventricular structure and function.

Comparative phylogenetic analysis of oolong tea (Phoenix Dancong tea) using complete chloroplast genome sequences.

Phoenix Dancong tea, a variety of oolong tea, is produced in Chaozhou, Guangdong Province, China, and is characterized by numerous hybridizations and polyploidization. To assess the genetic diversity and phylogenetic relationships among Phoenix Dancong tea and other oolong teas, an integrated circular chloroplast genome was constructed for thirty species of Phoenix Dancong tea from Chaozhou. The genome of Phoenix dancong tea is a circular molecule of 157,041-157,137 bp, with a pair of inverted repeats (26,072-26,610 bp each) separated by a large single copy (86,615-86,658 bp) and small single copy (18,264-18,284 bp). A total of 135 unique genes were encoded, including 90 protein coding genes, 37 tRNAs and 8 rRNAs. A comparative analysis with the other seven species in the oolong tea family that have been sequenced to date revealed similarities in structural organization, gene content and arrangement. Repeated sequence analysis identified 17-23 tandem repeats, 20-24 forward repeats and 25-27 palindromic repeats. Additionally, a total of 65-70 simple sequence repeats were detected, with mononucleotide repeats being the most common. Phylogenetic analyses showed that Phoenix Dancong tea and Fujian oolong tea were clustered with other cultivated Camellia sinensis in the genus Camellia of the family Theaceae, while the two oolong tea species were relatively independently cross-embedded in the genus, Camellia. Close genetic relationships were observed between Phoenix Dancong tea and other oolong teas, and the overall chloroplast genomes of oolong tea showed patterns with low variations and conserved evolution. The availability of Phoenix Dancong tea chloroplast genomes not only elucidated the relationship among oolong teas from different origins in Guangdong and Fujian but also provided valuable genetic resources to assist further molecular studies on the taxonomic and phylogenomic resolution of the genus Camellia.

MSCs Therapy Reverse the Gut Microbiota in Hypoxia-Induced Pulmonary Hypertension Mice.

Mesenchymal stem cell (MSC) therapy is a promising therapeutic approach based on its strong effect on pulmonary hypertension (PH) in rats. However, the detailed mechanism of MSC therapy remains unknown. Alterations in the gut microbiota were found in both type 1 pulmonary arterial hypertension patients and hypoxia/SU5416- or monocrotaline (MCT)-induced PH rats. However, whether the therapeutic mechanism of MSCs is associated with the gut microbiota is poorly understood. Here, we found that gut microbiota homeostasis was disrupted in hypoxia-induced PH mice due to the increased Firmicutes-to-Bacteroidetes (F/B) ratio; enhanced abundances of harmful Marinifilaceae, Helicobacteraceae, and Lactobacillaceae; and decreased abundances of beneficial Bacteroidaceae, Prevotellaceae, Tannerellaceae, and Lachnospiraceae. Unexpectedly, reverses of the increase in disease-associated microbiota and decrease in anti-inflammatory and immunomodulatory functional microbiota were observed in the MSC-treated group. We also identified harmful Erysipelotrichaceae, Alphaproteobacteria, Christensenella timonensis, Coriobacteriales, and Rhodospirillales that may serve as gut microbiota biomarkers of hypoxia-induced PH mice. Micrococcaales, Nesterenkonia, Anaerotruncus, and Tyzzerella may serve as gut microbiota biomarkers of MSC-treated mice. In summary, MSC treatment suppresses hypoxia-induced pulmonary hypertension in mice, and alterated gut microbiota may play a role in the development and progression of PH. The mechanism of MSC therapy is associated with various metabolic pathways of the gut microbiota in hypoxia model PH mice.

Calycosin inhibits breast cancer cell migration and invasion by suppressing EMT via BATF/TGF-ß1.

In this study, we investigated the effects of calycosin on breast cancer cell progression and their underlying mechanisms. Calycosin dose- and time-dependently inhibited proliferation, migration, and invasion by T47D and MCF-7 breast cancer cells by downregulating basic leucine zipper ATF-like transcription factor (BATF) expression. Moreover, BATF promoted breast cancer cell migration and invasiveness by increasing TGFß1 mRNA and protein levels. Bioinformatics analysis, dual luciferase reporter assays, and chromatin immunoprecipitation assays confirmed the presence of BATF-binding sites in the promoter sequence of TGFß1 gene. Calycosin treatment inhibited epithelial-mesenchymal transition (EMT) of breast cancer cells by significantly increasing E-cadherin levels and decreasing N-cadherin, Vimentin, CD147, MMP-2, and MMP-9 levels through downregulation of BATF and TGFß1. TGFß1 knockdown reduced the migration and invasiveness of BATF-overexpressing breast cancer cells, whereas incubation with TGFß1 enhanced the migration and invasiveness of calycosin-treated breast cancer cells. Our findings demonstrated that calycosin inhibited EMT and progression of breast cancer cells by suppressing BATF/TGFß1 signaling. This suggests calycosin would be a promising therapeutic option for breast cancer patients.

The Mechanisms of Yu Ping Feng San in Tracking the Cisplatin-Resistance by Regulating ATP-Binding Cassette Transporter and Glutathione S-Transferase in Lung Cancer Cells.

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs.

Different clinical parameters inform epicardial fat thickness in pre- and post-menopausal women with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a sleep-related disorder with breathing difficulties. Previous studies revealed that epicardial fat thickness (EFT) correlates with OSA severity. Interestingly, female patients display a stronger EFT-OSA correlation than males. The purpose of this study is to investigate the relationship between EFT and different clinical characteristics in pre- and post-menopausal women diagnosed with OSA. METHODS: Patients diagnosed with OSA were divided into pre/early peri-menopausal (Group 1) and post/late peri-menopausal (Group 2) according to the menopause status. EFT was obtained from parasternal long-axis echocardiographic images. We also collected general clinical characteristics of patients involved in this study, and performed spearman correlation analysis to explore the correlations between EFT and the general clinical characteristics. We further applied Multiple stepwise linear regression analysis to explore the predictors for EFT in both groups. RESULTS: A total number of 23 and 59 patients were enrolled in Group 1 and Group 2 respectively. EFT in Group 2 was significantly higher than that of Group 1. In both groups, EFT was positively correlated with apnea-hypopnea index (AHI), percentage of total sleep time when blood oxygen saturation was less than 90% (T90), oxygen desaturation index (ODI) and glucose; while EFT was negatively correlated with mean and lowest SaO2 (oxygen saturation) levels. However, EFT was positively correlated with total cholesterol (TC) only in Group 1 and body mass index (BMI) only in Group2, respectively. Multiple stepwise linear regression analysis showed that AHI was independently associated with EFT in Group 1. However, both AHI and BMI were independent predictors of EFT in Group 2. CONCLUSION: EFT was notably correlated with menopausal status in women with OSA. AHI was the independent predictor of EFT in women with OSA. BMI was the independent predictor of EFT in post/late peri-menopausal women with OSA.

The impact of left ventricular geometry on left atrium phasic function in obstructive sleep apnea syndrome: a multimodal echocardiography investigation.

BACKGROUND: Left ventricular geometry and left atrium (LA) enlargement are risk factors for cardiovascular disease. However, reports on the relationship between left ventricular geometry and LA volume yielded contradictory findings, and LA phasic function remains unclear. Hence, this study aimed to investigate the influence of left ventricular geometry on LA volume and phasic function in patients with obstructive sleep apnea syndrome (OSAS) via a multimodal echocardiographic approach. METHODS: In this cross-sectional study, 221 patients with OSAS (age 20-68 years, mean age 45.27 ± 12.50 years) underwent clinical evaluation, polysomnography, and multimodal echocardiographic examination with two-dimensional echocardiography (2DE), two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE). Based on conventional classification of left ventricular geometry, patients with OSAS were divided into four groups: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). RESULTS: Based on 2DE and 3DE, the LA volumes and indices gradually increased from NG to CH. Additionally, 2DE and 3DE LA maximum volume index (LAVImax) were higher in patients with CH and EH than in patients with NG and CR (P < 0.05). The reservoir function, estimated by LA total emptying fraction (LA TotEF) was lower in patients with CH than in patients with NG in 2DE and 3DE (both, P < 0.05). Also, LA conduit function, evaluated by LA passive emptying fraction (LA PassEF) was lower in patients with CH than in patients with NG and CR, and in patients with EH than in those with NG in 2DE and 3DE (all, P < 0.05). The LA booster pump function, evaluated by LA active emptying fraction (LA ActEF) showed no statistically significant difference in 2DE; however, it was greater in patients with CH than in those with NG in 3DE. Similar results were obtained by 2D-STE, and CH was significantly associated with LA strain during systole (LAS-S, ß = - 0.546, 95%CI: - 6.371-(- 3.444); P < 0.001), early diastole (LAS-E, ß = - 0.636, 95%CI: - 9.532-(- 5.710); P < 0.001), and late diastole (LAS-A, ß = - 0.450, 95%CI: 1.518-3.909; P < 0.001) in multiple linear regression. CONCLUSIONS: The LA phasic function changed with left ventricular geometry via multimodal echocardiography. CH had the most notable negative effect on the maximum volume and phasic function of the LA.

Directional axonal regrowth induced by an aligned fibrin nanofiber hydrogel contributes to improved motor function recovery in canine L2 spinal cord injury.

Spinal cord injuries (SCI) normally disrupt the long axonal tracts of the spinal cord and cause permanent neurological deficits, for which there is currently a lack of effective therapeutic methods. Biomaterial-based regenerative medicine is a pivotal strategy to induce axonal regeneration through delivery of biophysical and/or biochemical regulatory cues by biomaterials. We previously fabricated a hierarchically aligned fibrin hydrogel (AFG) that could promote neurogenic differentiation of stem cells in vitro and has been successfully applied for peripheral nerve and spinal cord regeneration in rats. In this study, AFG was used to repair a canine lumbar segment 2 hemisection spinal cord injury, and the consistency of histological, imageological and behavioral results was compared. AFG was used to construct an aligned fiber bridge that supported cell adhesion in vitro and rapidly facilitated tissue invasion along the long axis of fibers in vivo, Moreover, in vivo results demonstrated regrowth of axons in an oriented pattern connecting the rostral and caudal stumps. Consistent results were confirmed by diffusion tensor imaging, which allowed successful tracing of reconnected nerve fibers across the defect. As a result, directional axonal regrowth contributed to significantly improved recovery of motor functional behavior of SCI canines with AFG implantation. Our results suggest that AFG has great promise for rapidly directing axonal regrowth for nerve regeneration.