Application of radiomics model based on ultrasound image features in the prediction of carpal tunnel syndrome severity.

OBJECTIVE: The aim of our study is to develop and validate a radiomics model based on ultrasound image features for predicting carpal tunnel syndrome (CTS) severity. METHODS: This retrospective study included 237 CTS hands (106 for mild symptom, 68 for moderate symptom and 63 for severe symptom). There were no statistically significant differences among the three groups in terms of age, gender, race, etc. The data set was randomly divided into a training set and a test set in a ratio of 7:3. Firstly, a senior musculoskeletal ultrasound expert measures the cross-sectional area of median nerve (MN) at the scaphoid-pisiform level. Subsequently, a recursive feature elimination (RFE) method was used to identify the most discriminative radiomic features of each MN at the entrance of the carpal tunnel. Eventually, a random forest model was employed to classify the selected features for prediction. To evaluate the performance of the model, the confusion matrix, receiver operating characteristic (ROC) curves, and F1 values were calculated and plotted correspondingly. RESULTS: The prediction capability of the radiomics model was significantly better than that of ultrasound measurements when 10 robust features were selected. The training set performed perfect classification with 100% accuracy for all participants, while the testing set performed accurate classification of severity for 76.39% of participants with F1 values of 80.00, 63.40, and 84.80 for predicting mild, moderate, and severe CTS, respectively. Comparably, the F1 values for mild, moderate, and severe CTS predicted based on the MN cross-sectional area were 76.46, 57.78, and 64.00, respectively.. CONCLUSION: This radiomics model based on ultrasound images has certain value in distinguishing the severity of CTS, and was slightly superior to using only MN cross-sectional area for judgment. Although its diagnostic efficacy was still inferior to that of neuroelectrophysiology. However, this method was non-invasive and did not require additional costs, and could provide additional information for clinical physicians to develop diagnosis and treatment plans.

Identification of miRNA858 long-loop precursors in seed plants.

MicroRNAs (miRNAs) are a class of nonprotein-coding short transcripts that provide a layer of post-transcriptional regulation essential to many plant biological processes. MiR858, which targets the transcripts of MYB transcription factors, can affect a range of secondary metabolic processes. Although miR858 and its 187-nt precursor have been well studied in Arabidopsis (Arabidopsis thaliana), a systematic investigation of miR858 precursors and their functions across plant species is lacking due to a problem in identifying the transcripts that generate this subclass. By re-evaluating the transcript of miR858 and relaxing the length cut-off for identifying hairpins, we found in kiwifruit (Actinidia chinensis) that miR858 has long-loop hairpins (1,100 to 2,100 nt), whose intervening sequences between miRNA generating complementary sites were longer than all previously reported miRNA hairpins. Importantly, these precursors of miR858 containing long-loop hairpins (termed MIR858L) are widespread in seed plants including Arabidopsis, varying between 350 and 5,500 nt. Moreover, we showed that MIR858L has a greater impact on proanthocyanidin and flavonol levels in both Arabidopsis and kiwifruit. We suggest that an active MIR858L-MYB regulatory module appeared in the transition of early land plants to large upright flowering plants, making a key contribution to plant secondary metabolism.

The value of radiomics model based on ultrasound image features in the differentiation between minimal breast cancer and small benign breast masses.

BACKGROUND: Female breast cancer has surpassed lung cancer as the most common cancer, and is also the main cause of cancer death for women worldwide. Breast cancer <1 cm showed excellent survival rate. However, the diagnosis of minimal breast cancer (MBC) is challenging. OBJECTIVE: The purpose of our research is to develop and validate an radiomics model based on ultrasound images for early recognition of MBC. METHODS: 302 breast masses with a diameter of <10 mm were retrospectively studied, including 159 benign and 143 malignant breast masses. The radiomics features were extracted from the gray-scale ultrasound image of the largest face of each breast mass. The maximum relevance minimum reduncancy and recursive feature elimination methods were used to screen. Finally, 10 features with the most discriminating value were selected for modeling. The random forest was used to establish the prediction model, and the rad-score of each mass was calculated. In order to evaluate the effectiveness of the model, we calculated and compared the area under the curve (AUC) value, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the model and three groups with different experience in predicting small breast masses, and drew calibration curves and decision curves to test the stability and consistency of the model. RESULTS: When we selected 10 radiomics features to calculate the rad-score, the prediction efficiency was the best, the AUC values for the training set and testing set were 0.840 and 0.793, which was significantly better than the insufficient experience group (AUC = 0.673), slightly better than the moderate experience group (AUC = 0.768), and was inferior to the experienced group (AUC = 0.877). The calibration curve and decision curve also showed that the radiomics model had satisfied stability and clinical application value. CONCLUSION: The radiomics model based on ultrasound image features has a satisfied predictive ability for small breast masses, and is expected to become a potential tool for the diagnosis of MBC, and it is a zero cost (in terms of patient participation and imaging time).

Application of ultrasound images-based radiomics in carpal tunnel syndrome: Without measuring the median nerve cross-sectional area.

PURPOSE: By constructing a prediction model of carpal tunnel syndrome (CTS) based on ultrasound images, it can automatically and accurately diagnose CTS without measuring the median nerve cross-sectional area (CSA). METHODS: A total of 268 wrists ultrasound images of 101 patients diagnosed with CTS and 76 controls in Ningbo NO.2 Hospital from December 2021 to August 2022 were retrospectively analyzed. The radiomics method was used to construct the Logistic model through the steps of feature extraction, feature screening, reduction, and modeling. The area under the receiver operating characteristic curve was calculated to evaluate the performance of the model, and the diagnostic efficiency of the radiomics model was compared with two radiologists with different experience. RESULTS: The 134 wrists in the CTS group included 65 mild CTS, 42 moderate CTS, and 17 severe CTS. In the CTS group, 28 wrists median nerve CSA were less than the cut-off value, 17 wrists were missed by Dr. A, 26 wrists by Dr. B, and only 6 wrists were missed by radiomics model. A total of 335 radiomics features were extracted from each MN, of which 10 features were significantly different between compressed and normal nerves, and were used to construct the model. The area under curve (AUC) value, sensitivity, specificity, and accuracy of the radiomics model in the training set and testing set were 0.939, 86.17%, 87.10%, 86.63%, and 0.891, 87.50%, 80.49%, and 83.95%, respectively. The AUC value, sensitivity, specificity, and accuracy of the two doctors in the diagnosis of CTS were 0.746, 75.37%, 73.88%, 74.63% and 0.679, 68.66%, 67.16%, and 67.91%, respectively. The radiomics model was superior to the two-radiologist diagnosis, especially when there was no significant change in CSA. CONCLUSION: Radiomics based on ultrasound images can quantitatively analyze the subtle changes in the median nerve, and can automatically and accurately diagnose CTS without measuring CSA, especially when there was no significant change in CSA, which was better than radiologists.

The Application of Ultrasound Image-Based Radiomics in the Diagnosis of Mild Carpal Tunnel Syndrome.

OBJECTIVES: The ultrasound diagnosis of mild carpal tunnel syndrome (CTS) is challenging. Radiomics can identify image information that the human eye cannot recognize. The purpose of our study was to explore the value of ultrasound image-based radiomics in the diagnosis of mild CTS. METHODS: This retrospective study included 126 wrists in the CTS group and 88 wrists in the control group. The radiomics features were extracted from the cross-sectional ultrasound images at the entrance of median nerve carpal tunnel, and the modeling was based on robust features. Two radiologists with different experiences diagnosed CTS according to two guidelines. The area under receiver (AUC) operating characteristic curve, sensitivity, specificity, and accuracy were used to evaluate the diagnostic efficacy of the two radiologists and the radiomics model. RESULTS: According to guideline one, the AUC values of the two radiologists for CTS were 0.72 and 0.67, respectively; according to guideline two, the AUC were 0.73 and 0.68, respectively. The radiomics model achieved the best accuracy when 16 important robust features were selected. The AUC values of training set and test set were 0.92 and 0.90, respectively. CONCLUSIONS: The radiomics label based on ultrasound images had excellent diagnostic efficacy for mild CTS. It is expected to help radiologists to identify early CTS patients as soon as possible, especially for inexperienced doctors.

Ultrasound-based radiomics in the diagnosis of carpal tunnel syndrome: The influence of regions of interest delineation method on mode.

BACKGROUND: In the recent years, artificial intelligence (AI) algorithms have been used to accurately diagnose musculoskeletal diseases. However, it is not known whether the particular regions of interest (ROI) delineation method would affect the performance of the AI algorithm. PURPOSE: The purpose of this study was to investigate the influence of ROI delineation methods on model performance and observer consistency. METHODS: In this retrospective analysis, ultrasound (US) measures of median nerves affected with carpal tunnel syndrome (CTS) were compared to median nerves in a control group without CTS. Two methods were used for delineation of the ROI: (1) the ROI along the hyperechoic medial edge of the median nerve but not including the epineurium (MN) (ROI1); and (2) the ROI including the hyperechoic epineurium (ROI2), respectively. The intra group correlation coefficient (ICC) was used to compare the observer consistency of ROI features (i.e. the corresponding radiomics parameters). Parameters α1 and α2 were obtained based on the ICC of ROI1 features and ROI2 features. The ROC analysis was used to determine the area under the curve (AUC) and evaluate the performance of the radiologists and network. In addition, four indices, namely sensitivity, specificity, positive prediction and negative prediction were analyzed too. RESULTS: A total of 136 wrists of 77 CTS group and 136 wrists of 74 control group were included in the study. Control group was matched to CTS group according to the age and sex. The observer consistency of ROI features delineated by the two schemes was different, and the consistency of ROI1 features was higher (α1 Ëƒ α2). The intra-observer consistency was higher than the inter-observer consistency regardless of the scheme, and the intra-observer consistency was higher when chose scheme one. The performances of models based on the two ROI features were different, although the AUC of each model was greater than 0.8.The model performed better when the MN epineurium was included in the ROI. Among five artificial intelligence algorithms, the Forest models (model1 achieved an AUC of 0.921 in training datasets and 0.830 in testing datasets; model2 achieved an AUC of 0.967 in training datasets and 0.872 in testing datasets.) obtained the highest performance, followed by the support vector machine (SVM) models and the Logistic models. The performances of the models were significantly better than the inexperienced radiologist (Dr. B. Z. achieved an AUC of 0.702). CONCLUSION: Different ROI delineation methods may affect the performance of the model and the consistency of observers. Model performance was better when the ROI contained the MN epineurium, and observer consistency was higher when the ROI was delineated along the hyperechoic medial border of the MN.

Chimonanthus salicifolius attenuated vascular remodeling by alleviating endoplasmic reticulum stress in spontaneously hypertensive rats.

Chimonanthus salicifolius (CS), the leaves of Chimonanthus salicifolius S. Y. Hu., is an effective tea to prevent and treat hypertension in China. This study aimed to explore the effect and mechanism of CS in the protection against vascular remodeling in hypertension. Spontaneously hypertensive rats (SHRs) were orally administered with aqueous extracts of CS for 6 months. The blood pressure and morphological changes of the aorta were measured. Their mechanisms were studied by combining chemical identification, network pharmacology analysis and validation in vivo. Hypertensive rats showed an impaired vascular structure and dyslipidemia as illustrated by the increase of the vascular media thickness and collagen deposition in the aorta. CS treatment exhibited significant beneficial effects on blood pressure control and aortal morphology. A total of 21 compounds from CS were identified, which were linked to 106 corresponding targeted genes for vascular remodeling. The network pharmacology predicted that CS prevented vascular remodeling through the endoplasmic reticulum stress pathway. The in vivo experiments further showed that CS treatment upregulated Glucose-Regulated Protein 78 and downregulated CCAAT-enhancer-binding protein homologous protein at both mRNA and protein levels, paralleling reduced apoptotic cells in the arterial wall. Additionally, CS diminished the low-density lipoprotein cholesterol levels, total cholesterol contents and triglyceride/high-density lipoprotein cholesterol ratios in the sera of SHRs, which might also contribute to its protection of vessels. Collectively, CS protects against vascular modeling by suppressing endoplasmic reticulum stress-related apoptosis in hypertension, and it could be a potential agent for the prevention and treatment of vascular modeling.

A narrative review of the emerging role of lymphocyte antigen 6 complex locus K in cancer: from basic research to clinical practice.

OBJECTIVE: In this paper, we will discuss the structure, function and role of lymphocyte antigen 6 complex locus K (LY6K) in disease model, and highlight the new progress of LY6K in current clinical trials. It provides reference value for future basic research. BACKGROUND: Cancer is a global public health problem that must be solved. The ability of tumor cells to evade the antitumor immune response makes cancer research and treatment more difficult. LY6K is highly expressed in a variety of cancers, can stimulate the immune system, and has tumor specificity. At present, a large number of vaccines have entered clinical trials. METHODS: The PubMed, umin.ac.jp/ctr and Clinical Trials.gov databases were searched for LY6K published literature and clinical trials. The structure and function of LY6K and the current state of research on LY6K in human cancers were discussed to provide reference for further research. CONCLUSIONS: The LY6K gene has been shown to be highly expressed in a variety of tumor cells, driving tumorigenesis and progression, and is negatively correlated with poor prognosis in patients. At the same time, LY6K can stimulate the immune response of the body's immune cells. The study of LY6K-related vaccines in clinical trials also suggests that targeting LY6K may be a new direction for tumor immunotherapy.

Hirsutella sinensis fungus improves cardiac function in mouse model of heart failure.

Cordyceps sinensis, including Hirsutella sinensis, is a highly valuable traditional Chinese medicine and is used to treat patients with pulmonary heart disease in clinical practice. However, the underlying mechanisms of its effects remain unclear. In this study, a mouse model of heart failure established by non-thoracic, transverse aortic constriction (TAC) was developed to determine the underlying mechanisms of therapeutic effects of Hirsutella sinensis fungus (HSF) powder. The results showed that HSF treatment remarkably ameliorated myocardial hypertrophy, collagen fiber hyperplasia, and cardiac function in mice with heart failure. Using transcriptional and epigenetic analyses, we found that the mechanism of HSF mainly involved a variety of signaling pathways related to myocardial fibrosis and determined that HSF could reduce the levels of TGF-ß1 proteins in heart tissue, as well as type I and III collagen levels. These data suggest that HSF alleviates heart failure, inhibits irreversible ventricular remodeling, and improves cardiac function through the regulation of myocardial fibrosis-related signaling pathways, which can provide novel opportunities to improve heart failure therapy.

Inhibition of histamine receptor H3 suppresses the growth and metastasis of human non-small cell lung cancer cells via inhibiting PI3K/Akt/mTOR and MEK/ERK signaling pathways and blocking EMT.

Recent evidence shows that the expression levels of histamine receptor H3 (Hrh3) are upregulated in several types of cancer. However, the role of Hrh3 in non-small cell lung cancer (NSCLC) has not been elucidated. In the present study, we showed that the expression levels of Hrh3 were significantly increased in NSCLC samples, and high levels of Hrh3 were associated with poor overall survival (OS) in NSCLC patients. In five human NSCLC cell lines tested, Hrh3 was significantly upregulated. In NSCLC cell lines H1975, H460, and A549, Hrh3 antagonist ciproxifan (CPX, 10-80 µM) exerted moderate and concentration-dependent inhibition on the cell growth and induced apoptosis, whereas its agonist RAMH (80 µM) reversed these effects. Furthermore, inhibition of Hrh3 by CPX or siRNA retarded the migration and invasion of NSCLC cells through inhibiting epithelial-mesenchymal transition (EMT) progression via reducing the phosphorylation of PI3K/Akt/mTOR and MEK/ERK signaling pathways. In nude mice bearing H1975 cell xenograft or A549 cell xenograft, administration of CPX (3 mg/kg every other day, intraperitoneal) significantly inhibited the tumor growth with increased E-cadherin and ZO-1 expression and decreased Fibronectin expression in tumor tissue. In conclusion, this study reveals that Hrh3 plays an important role in the growth and metastasis of NSCLC; it might be a potential therapeutic target against the lung cancer.

Angiopep-2 modified lipid-coated mesoporous silica nanoparticles for glioma targeting therapy overcoming BBB.

Glioma is the most typical malignant brain tumor, and the chemotherapy to glioma is limited by poor permeability for crossing blood-brain-barrier (BBB) and insufficient availability. In this study, angiopep-2 modified lipid-coated mesoporous silica nanoparticle loading paclitaxel (ANG-LP-MSN-PTX) was developed to transport paclitaxel (PTX) across BBB mediated by low-density lipoprotein receptor-related protein 1 (LRP1), which is over-expressed on both BBB and glioma cells. ANG-LP-MSN-PTX was characterized with homogeneous hydrodynamic size, high drug loading capacity (11.08%) and a sustained release. In vitro experiments demonstrated that the targeting efficiency of PTX was enhanced by ANG-LP-MSN-PTX with higher penetration ability (10.74%) and causing more C6 cell apoptosis. ANG-LP-MSN-PTX (20.6%) revealed higher targeting efficiency compared with LP-MSN-PTX (10.6%) via blood and intracerebral microdialysis method in the pharmacokinetic study. The therapy of intracranial C6 glioma bearing rats was increasingly efficient, and ANG-LP-MSN-PTX could prolong the survival time of model rats. Taken together, ANG-LP-MSN-PTX might hold great promise as a targeting delivery system for glioma treatment.

Annexin A5 regulates hepatic macrophage polarization via directly targeting PKM2 and ameliorates NASH.

Nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease (NAFLD), is becoming a common chronic liver disease with the characteristics of steatosis, inflammation and fibrosis. Macrophage plays an important role in the development of NASH. In this study, Annexin A5 (Anx A5) is identified with the special effect on hepatic macrophage phenotype shift from M1 to M2. And it is further demonstrated that Anx A5 significantly switches metabolic reprogramming from glycolysis to oxidative phosphorylation in activated macrophages. Mechanistically, the main target of Anx A5 in energy metabolism is confirmed to be pyruvate kinase M2 (PKM2). And we following reveal that Anx A5 directly interacts with PKM2 at ASP101, LEU104 and ARG106, inhibits phosphorylation of Y105, and promotes PKM2 tetramer formation. In addition, based on the results of PKM2 inhibitor (compound 3k) and the phosphorylated mutation (PKM2 (Y105E)), it is proved that Anx A5 exhibits the function in macrophage polarization dependently on PKM2 activity. In vivo studies also show that Anx A5 improves steatosis, inflammation and fibrosis in NASH mice due to specially regulating hepatic macrophages via interaction with PKM2. Therefore, we have revealed a novel function of Anx A5 in hepatic macrophage polarization and HFD-induced NASH, providing important insights into the metabolic reprogramming, which is important for NASH therapy.

Monoterpenes-containing PEGylated transfersomes for enhancing joint cavity drug delivery evidenced by CLSM and double-sited microdialysis.

The synovial tissues are natural sites of drug delivery for the treatment of rheumatoid arthritis. Our previous study showed that mixed monoterpenes edge-activated PEGylated transfersomes (MMPTs) could significantly enhance the percutaneous absorption of sinomenine (SIN), an anti-inflammation drug. The aim of this study was to investigate the potential of MMPTs for delivery of SIN to the synovial tissues in joint cavities. To this end, conventional liposomes (LPSs) were used as a reference. Transmission electron microscope, constant pressure extrusion method, and differential scanning calorimetry (DSC) were used for physicochemical characterization of the formulations. Confocal laser scanning microscopy (CLSM) and double-sited microdialysis coupled with LC-MS/MS were exploited to study the distribution of MMPTs in different skin layers and pharmacokinetics of SIN in the blood and the joint cavities. The results showed that mixed monoterpenes could significantly enhance the elasticity of MMPTs, evidenced by a decrease in the main transition temperature (Tm) and transition enthalpy (△H). CLSM analyses demonstrated that MMPTs were distributed in deep layers of the skin, indicating that MMPTs might transport SIN through the skin. In contrast, LPSs were confined in the stratum corneum, which deterred SIN from penetrating through the skin. The results from double-sited microdialysis pharmacokinetics showed that in the joint cavities the steady state concentration (Css) and AUC0→t of SIN from MMPTs were 2.1-fold and 2.5-fold of those from LPSs, respectively. In contrast, in the blood the Css and AUC0→t of SIN from MMPTs were about 1/3 of those from LPSs. This study suggested that MMPTs could enhance the delivery of SIN to the joint cavities. A combination of CLSM and double-sited microdialysis could give an insight into the mechanism of transdermal and local drug delivery.

A Study on Acetylglutamine Pharmacokinetics in Rat Blood and Brain Based on Liquid Chromatography-Tandem Mass Spectrometry and Microdialysis Technique.

Acetylglutamine (NAG) is the derivative of glutamine, which is the richest free amino acid in the human body. In this work, a novel reliable method of the combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and microdialysis (MD) technique for the evaluation of NAG and its metabolites γ-aminobutyric acid (GABA) and glutamic acid (Glu) in rat blood and brain was proposed. A Zorbax SB-C18 column (2.1 × 100 mm, 3.5 µM) was applied to separate the analytes. The mobile phase was acetonitrile-water (70:30, v/v) containing 5 mM ammonium acetate and the flow rate was 0.3 ml/min. Based on the multiple reaction monitoring (MRM) mode of positive ion, the precursors of product ions chosen for NAG, Glu, GABA, and N-carbamyl-L-glutamic (NCG, IS) were (m/z) 189.1→130.0, 148.0→84.1, 104→87.1, and 191.0→130.1, respectively. All the validation data, including precision, accuracy, inter-day repeatability, matrix effect, and stability, were within the acceptable ranges according to the reference of Bioanalytical Method Validation Guidance for Industry (2018). Rats with microdialysis probes inserted into jugular vein and hippocampus were administered the low (75 mg/kg, NAG-L), medium (150 mg/kg, NAG-M), and high (300 mg/kg, NAG-H) doses of NAG and 10 ml/kg Guhong injection (GHI) by tail vein, respectively. In the blood test, the Cmax values of NAG-L group were markedly lower (P < 0.01) than those of NAG-M, NAG-H, and GHI groups, respectively. No differences were observed between NAG-M and GHI groups, while the Cmax values in GHI group were significantly upgraded compared with NAG-H group. There were notable differences in the Cmax values of NAG in brain dialysate after administration of NAG and GHI. The drug distribution coefficients of NAG, Glu, GABA in brain and blood at low, medium, high doses of NAG and GHI groups were 13.99, 27.43, 34.81, 31.37; 11.04, 59.07, 21.69, 2.69%; 212.88, 234.92, 157.59, and 102.65%, respectively. Our investigation demonstrates that NAG and its related metabolites in rat blood and brain can be simultaneously measured according to the above proposed method. Meanwhile, NAG has easy and dose-dependently access to the blood-brain barrier and exhibits a medium retention time in rat.

Fatty liver diseases, mechanisms, and potential therapeutic plant medicines.

The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins (SIRTs), Forkhead box O (FoxO), Sterol-regulatory element-binding proteins (SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.

Withdrawal Notice: Renoprotective Effect of Curcumin Labelled on Mesoscale Nanoparticles (MNPs) in Renal Ischemia-Reperfusion Injury (RIRI) via the miR-146a/nNOS/NO/cGMP/PKG Signaling Pathway

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Traditional Chinese Medicine for Coronary Heart Disease: Clinical Evidence and Possible Mechanisms.

Coronary heart disease (CHD) remains a major cause of mortality with a huge economic burden on healthcare worldwide. Here, we conducted a systematic review to investigate the efficacy and safety of Chinese herbal medicine (CHM) for CHD based on high-quality randomized controlled trials (RCTs) and summarized its possible mechanisms according to animal-based researches. 27 eligible studies were identified in eight database searches from inception to June 2018. The methodological quality was assessed using seven-item checklist recommended by Cochrane Collaboration. All the data were analyzed using Rev-Man 5.3 software. As a result, the score of study quality ranged from 4 to 7 points. Meta-analyses showed CHM can significantly reduce the incidence of myocardial infarction and percutaneous coronary intervention, and cardiovascular mortality (P < 0.05), and increase systolic function of heart, the ST-segment depression, and clinical efficacy (P < 0.05). Adverse events were reported in 11 studies, and CHMs were well tolerated in patients with CHD. In addition, CHM exerted cardioprotection for CHD, possibly altering multiple signal pathways through anti-inflammatory, anti-oxidation, anti-apoptosis, improving the circulation, and regulating energy metabolism. In conclusion, the evidence available from present study revealed that CHMs are beneficial for CHD and are generally safe.

An Updated Review of Disulfiram: Molecular Targets and Strategies for Cancer Treatment.

Repurposing already approved drugs as new anticancer agents is a promising strategy considering the advantages such as low costs, low risks and less time-consumption. Disulfiram (DSF), as the first drug for antialcoholism, was approved by the U.S. Food and Drug Administration (FDA) over 60 years ago. Increasing evidence indicates that DSF has great potential for the treatment of various human cancers. Several mechanisms and targets of DSF related to cancer therapy have been proposed, including the inhibition of ubiquitin-proteasome system (UPS), cancer cell stemness and cancer metastasis, and alteration of the intracellular reactive oxygen species (ROS). This article provides a brief review about the history of the use of DSF in humans and its molecular mechanisms and targets of anticancer therapy, describes DSF delivery strategies for cancer treatment, summarizes completed and ongoing cancer clinical trials involving DSF, and offers strategies to better use DSF in cancer therapies.

Buyang Huanwu Decoction Exerts Cardioprotective Effects through Targeting Angiogenesis via Caveolin-1/VEGF Signaling Pathway in Mice with Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The idea of therapeutic angiogenesis in ischemic myocardium is a promising strategy for MI patients. Buyang Huanwu decoction (BHD), a famous Chinese herbal prescription, exerted antioxidant, antiapoptotic, and anti-inflammatory effects, which contribute to cardio-/cerebral protection. Here, we aim to investigate the effects of BHD on angiogenesis through the caveolin-1 (Cav-1)/vascular endothelial growth factor (VEGF) pathway in MI model of mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into 3 groups by the table of random number: (1) sham-operated group (sham, n = 15), (2) AMI group (AMI+sham, n = 20), and (3) BHD-treated group (AMI+BHD, n = 20). 2,3,5-Triphenyltetrazolium chloride solution stain was used to determine myocardial infarct size. Myocardial histopathology was tested using Masson staining and hematoxylin-eosin staining. CD31 immunofluorescence staining was used to analyze the angiogenesis in the infarction border zone. Western blot analysis, immunofluorescence staining, and/or real-time quantitative reverse transcription polymerase chain reaction was applied to test the expression of Cav-1, VEGF, vascular endothelial growth factor receptor 2 (VEGFR2), and/or phosphorylated extracellular signal-regulated kinase (p-ERK). All statistical analyses were performed using the SPSS 20.0 software and GraphPad Prism 6.05. Values of P < 0.05 were considered as statistically significant. RESULTS AND CONCLUSION: Compared with the AMI group, the BHD-treated group showed a significant improvement in the heart weight/body weight ratio, echocardiography images, cardiac function, infarct size, Mason staining of the collagen deposition area, and density of microvessel in the infarction border zone (P < 0.05). Compared with the AMI group, BHD promoted the expression of Cav-1, VEGF, VEGFR2, and p-ERK in the infarction border zone after AMI. BHD could exert cardioprotective effects on the mouse model with AMI through targeting angiogenesis via Cav-1/VEGF signaling pathway.

5, 7, 2', 4', 5'-Pentamethoxyflavanone regulates M1/M2 macrophage phenotype and protects the septic mice.

Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1ß, IL-6, TNF-α and iNOS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.