Brain functional connectivity alterations of Wernicke's area in individuals with autism spectrum conditions in multi-frequency bands: A mega-analysis.

Characterized by severe deficits in communication, most individuals with autism spectrum conditions (ASC) experience significant language dysfunctions, thereby impacting their overall quality of life. Wernicke's area, a classical and traditional brain region associated with language processing, plays a substantial role in the manifestation of language impairments. The current study carried out a mega-analysis to attain a comprehensive understanding of the neural mechanisms underpinning ASC, particularly in the context of language processing. The study employed the Autism Brain Image Data Exchange (ABIDE) dataset, which encompasses data from 443 typically developing (TD) individuals and 362 individuals with ASC. The objective was to detect abnormal functional connectivity (FC) between Wernicke's area and other language-related functional regions, and identify frequency-specific altered FC using Wernicke's area as the seed region in ASC. The findings revealed that increased FC in individuals with ASC has frequency-specific characteristics. Further, in the conventional frequency band (0.01-0.08 Hz), individuals with ASC exhibited increased FC between Wernicke's area and the right thalamus compared with TD individuals. In the slow-5 frequency band (0.01-0.027 Hz), increased FC values were observed in the left cerebellum Crus II and the right lenticular nucleus, pallidum. These results provide novel insights into the potential neural mechanisms underlying communication deficits in ASC from the perspective of language impairments.

[Change in Granulation Potential and Microbial Enrichment Characteristics of Sludge Induced by Microplastics].

Microplastics (MPs), as a new type of pollutant, are widely detected in sewage treatment plants. Currently, research on MPs in traditional sewage treatment systems has mainly been focused on the pollution level and distribution characteristics, with a lack of studying the impact of MPs on the sludge granulation. In order to explore the effect of MPs on the granulation process, a microplastic exposure test was conducted by adding polyethylene terephthalate microplastics (PET-MPs), which are widespread in the environment. The operating performance of the system, extracellular polymeric substance (EPS) composition, and flora enrichment were analyzed on the sludge granulation. The results showed that the exposure of PET-MPs significantly accelerated the sludge granulation process, whereas the increase in EPS content dominated by PN enhanced the sludge surface hydrophobicity; the granulation rate and EPS secretion were proportional to the exposed particle size. Microplastics and EPS secretions synergistically promoted the formation of granular sludge. However, continuous microplastic exposure led to deterioration of the system decontamination performance and inhibited the degradation process of pollutants, with the most negative effect of nitrite nitrogen accumulation under 250 µm PET-MPs exposure, as high as (5.08±0.24) mg·L-1. The high-throughput sequencing revealed that the microbial community diversity fell in the experimental group. The dominant bacteria at the phylum level were Proteobacteria and Bacteroidota on the sludge granulation. Rhodocyclaceae, Sphingomonadaceae, Flavobacteriaceae, and Rhodanobacteraceae promoted flocculation by increasing EPS secretion. The decrease in Comamonadaceae and Chitinophagaceae weakened the ammonia and nitrite oxidation capacity of the system, whereas the decrease in Rhodobacteraceae, Hyphomonadaceae, and Xanthomonadaceae inhibited the removal of nitrate nitrogen.

Exploration of the Shared Hub Genes and Biological Mechanism in Osteoporosis and Type 2 Diabetes Mellitus based on Machine Learning.

A substantial amount of evidence suggests a close relationship between osteoporosis (OP) and Type 2 Diabetes Mellitus (T2DM), but the mechanisms involved remain unknown. Therefore, we conducted this study with the aim of screening for hub genes common to both diseases and conducting a preliminary exploration of common regulatory mechanisms. In the present study, we first screened genes significantly associated with OP and T2DM by the univariate logistic regression algorithm. And then, based on cross-analysis and random forest algorithm, we obtained three hub genes (ACAA2, GATAD2A, and VPS35) and validated the critical roles and predictive performance of the three genes in both diseases by differential expression analysis, receiver operating characteristic (ROC) curves, and genome wide association study (GWAS) analysis. Finally, based on gene set enrichment analysis (GSEA) and the construction of the miRNA-mRNA regulatory network, we conducted a preliminary exploration of the co-regulatory mechanisms of three hub genes in two diseases. In conclusion, this study provides promising biomarkers for predicting and treating both diseases and offers novel directions for exploring the common regulatory mechanisms of both diseases.

Fisetin treatment alleviates kidney injury in mice with diabetes-exacerbated atherosclerosis through inhibiting CD36/fibrosis pathway.

Diabetes-related vascular complications include diabetic cardiovascular diseases (CVD), diabetic nephropathy (DN) and diabetic retinopathy, etc. DN can promote the process of end-stage renal disease. On the other hand, atherosclerosis accelerates kidney damage. It is really an urge to explore the mechanisms of diabetes-exacerbated atherosclerosis as well as new agents for treatment of diabetes-exacerbated atherosclerosis and the complications. In this study we investigated the therapeutic effects of fisetin, a natural flavonoid from fruits and vegetables, on kidney injury caused by streptozotocin (STZ)-induced diabetic atherosclerosis in low density lipoprotein receptor deficient (LDLR-/-) mice. Diabetes was induced in LDLR-/- mice by injecting STZ, and the mice were fed high-fat diet (HFD) containing fisetin for 12 weeks. We found that fisetin treatment effectively attenuated diabetes-exacerbated atherosclerosis. Furthermore, we showed that fisetin treatment significantly ameliorated atherosclerosis-enhanced diabetic kidney injury, evidenced by regulating uric acid, urea and creatinine levels in urine and serum, and ameliorating morphological damages and fibrosis in the kidney. In addition, we found that the improvement of glomerular function by fisetin was mediated by reducing the production of reactive oxygen species (ROS), advanced glycosylation end products (AGEs) and inflammatory cytokines. Furthermore, fisetin treatment reduced accumulation of extracellular matrix (ECM) in the kidney by inhibiting the expression of vascular endothelial growth factor A (VEGFA), fibronectin and collagens, while enhancing matrix metalloproteinases 2 (MMP2) and MMP9, which was mainly mediated by inactivating transforming growth factor ß (TGFß)/SMAD family member 2/3 (Smad2/3) pathways. In both in vivo and in vitro experiments, we demonstrated that the therapeutic effects of fisetin on kidney fibrosis resulted from inhibiting CD36 expression. In conclusion, our results suggest that fisetin is a promising natural agent for the treatment of renal injury caused by diabetes and atherosclerosis. We reveal that fisetin is an inhibitor of CD36 for reducing the progression of kidney fibrosis, and fisetin-regulated CD36 may be a therapeutic target for the treatment of renal fibrosis.

Abnormal amygdala functional connectivity and deep learning classification in multifrequency bands in autism spectrum disorder: A multisite functional magnetic resonance imaging study.

Previous studies have explored resting-state functional connectivity (rs-FC) of the amygdala in patients with autism spectrum disorder (ASD). However, it remains unclear whether there are frequency-specific FC alterations of the amygdala in ASD and whether FC in specific frequency bands can be used to distinguish patients with ASD from typical controls (TCs). Data from 306 patients with ASD and 314 age-matched and sex-matched TCs were collected from 28 sites in the Autism Brain Imaging Data Exchange database. The bilateral amygdala, defined as the seed regions, was used to perform seed-based FC analyses in the conventional, slow-5, and slow-4 frequency bands at each site. Image-based meta-analyses were used to obtain consistent brain regions across 28 sites in the three frequency bands. By combining generative adversarial networks and deep neural networks, a deep learning approach was applied to distinguish patients with ASD from TCs. The meta-analysis results showed frequency band specificity of FC in ASD, which was reflected in the slow-5 frequency band instead of the conventional and slow-4 frequency bands. The deep learning results showed that, compared with the conventional and slow-4 frequency bands, the slow-5 frequency band exhibited a higher accuracy of 74.73%, precision of 74.58%, recall of 75.05%, and area under the curve of 0.811 to distinguish patients with ASD from TCs. These findings may help us to understand the pathological mechanisms of ASD and provide preliminary guidance for the clinical diagnosis of ASD.

Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway.

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 µM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

The White Matter Functional Abnormalities in Patients with Transient Ischemic Attack: A Reinforcement Learning Approach.

Background: Transient ischemic attack (TIA) is a known risk factor for stroke. Abnormal alterations in the low-frequency range of the gray matter (GM) of the brain have been studied in patients with TIA. However, whether there are abnormal neural activities in the low-frequency range of the white matter (WM) in patients with TIA remains unknown. The current study applied two resting-state metrics to explore functional abnormalities in the low-frequency range of WM in patients with TIA. Furthermore, a reinforcement learning method was used to investigate whether altered WM function could be a diagnostic indicator of TIA. Methods: We enrolled 48 patients with TIA and 41 age- and sex-matched healthy controls (HCs). Resting-state functional magnetic resonance imaging (rs-fMRI) and clinical/physiological/biochemical data were collected from each participant. We compared the group differences between patients with TIA and HCs in the low-frequency range of WM using two resting-state metrics: amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The altered ALFF and fALFF values were defined as features of the reinforcement learning method involving a Q-learning algorithm. Results: Compared with HCs, patients with TIA showed decreased ALFF in the right cingulate gyrus/right superior longitudinal fasciculus/left superior corona radiata and decreased fALFF in the right cerebral peduncle/right cingulate gyrus/middle cerebellar peduncle. Based on these two rs-fMRI metrics, an optimal Q-learning model was obtained with an accuracy of 82.02%, sensitivity of 85.42%, specificity of 78.05%, precision of 82.00%, and area under the curve (AUC) of 0.87. Conclusion: The present study revealed abnormal WM functional alterations in the low-frequency range in patients with TIA. These results support the role of WM functional neural activity as a potential neuromarker in classifying patients with TIA and offer novel insights into the underlying mechanisms in patients with TIA from the perspective of WM function.

Clinical Effect of Abdominal Massage Therapy on Blood Glucose and Intestinal Microbiota in Patients with Type 2 Diabetes.

The aim of the study was to investigate the clinical effects of abdominal massage on patients with type 2 diabetes mellitus (T2DM) and its influence on the intestinal microflora. We conducted a randomized, controlled clinical trial. A total of 60 patients with T2DM, who met the inclusion criteria, were randomly allocated to the control group, the routine massage group, and the abdominal massage group. The control group received health education and maintained their hypoglycemic drug treatment plan. The routine massage group and the abdominal massage group received different massage interventions. In addition to glucose and lipid metabolism indicators, we quantitatively analyzed the gut microbiota to assess the effects of massage on the intestinal microflora of patients with T2DM. Compared with the control group, the abdominal massage improved levels of glycated hemoglobin, total cholesterol, Enterobacter, and Bifidobacteria with significant differences (P = 0.02, P = 0.03, P = 0.03, and P = 0.03). The comparison within group showed that the levels of the four bacterial genera in the abdominal massage group revealed significant differences before and after treatment (P = 0.006, P < 0.001, P < 0.001, and P = 0.002). The comparison between the routine massage group and the abdominal massage group was not significantly different in all levels of test indices. The abdominal massage group regulated levels of Enterobacter and Lactobacilli to a greater extent than the routine massage group. Additionally, abdominal massage decreased Enterococcus levels. The results of this study showed that abdominal massage has clinical advantages over routine massage. Specifically, this intervention may correct microflora disturbances to a certain extent.

Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

Effective components and mechanism analysis of anti-platelet aggregation effect of Justicia procumbens L.

ETHNOPHARMACOLOGICAL RELEVANCE: Justicia procumbens L. is a traditional Chinese medicine, first recorded in "Shen Nong's Herbal Classic", for the treatment of lumbar pain and fever. As a widely distributed herb, it has also been documented in India, Nepal, and Malaysia. In "Tang Materia Medica", a famous medicinal book of Tang Dynasty in ancient China, it was first used to treat diseases associated with blood stasis. Blood stasis syndrome is closely related to thrombus formation and platelet aggregation. Although some compounds isolated from this plant have anti-platelet aggregation effects, the main chemical components and mechanism of J. procumbens in terms of these effects are little known. AIMS OF THE STUDY: Through in vivo and in vitro experiments, this studsy revealed the characteristic components and action mechanism of anti-platelet aggregation by J. procumbens from an overall perspective. MATERIALS AND METHODS: The effective crude extracts of the whole plant were screened via an in vitro anti-platelet aggregation test. After incubating these extracts with apheresis platelets, high affinity compounds were detected by HPLC-MS and regulatory genes were detected using gene chips. The effective components and potential target proteins were analyzed using computational docking technology. Furthermore, the compound with the strongest predicted activity was evaluated in vivo via an anti-thrombotic test. RESULTS: Integrin aⅡbß3, PKCα, PI3Kγ, and mitogen-activated protein kinase 14 were found to be potential targets. Justicidin B, tuberculatin, chinensinaphthol methyl ether, and neojusticin B were effective compounds that inhibited human platelet aggregation by suppressing Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways. Among the compounds that bind to platelets, justicidin B showed the strongest virtual binding force. The test of carotid artery thrombosis induced by ferric chloride in SD rats confirmed that justicidin B inhibited thrombus formation. CONCLUSION: Experimental investigation showed that arylnaphthalene lignan aglycones with one methylenedioxy group and two methoxy groups are effective components for anti-platelet aggregation by J. procumbens. These compounds inhibit Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways by suppressing the expression of genes such as ITGB3, PRKCA, PIK3CG, and MAPK14. These results reflected the characteristics of multi-component and multi-target synergistic treatment of Chinese medicine.

Prolonged Viral Shedding in Three Young Adult Cases of COVID-19.

Severe acute respiratory syndrome coronavirus-2 infection is usually self-limited, with a short duration for viral shedding within several weeks. However, prolonged viral shedding has been observed in severe or immune-compromised coronavirus disease 2019 (COVID-19) cases. Here, we reported that three young adult cases of COVID-19 patients, who were either immunosuppressed nor severe, showed prolonged viral RNA shedding from the upper respiratory tract for 58, 81, and 137 days since initial diagnosis. To our knowledge, this is the longest duration of viral shedding reported to date in young adult patients. Further studies on factors relevant to prolonged viral positivity, as well as the correlation between viral positivity and transmission risk are needed for the optimal management of COVID-19 patients with prolonged nucleic acid positive.

Altered Local Brain Amplitude of Fluctuations in Patients With Myotonic Dystrophy Type 1.

This study is aimed at investigating the characteristics of the spontaneous brain activity in patients with myotonic dystrophy type 1 (DM1). A total of 18 patients with DM1 and 18 healthy controls (HCs) were examined by resting-state functional MRI. Combined methods include amplitude of low-frequency fluctuations (ALFFs), the fractional amplitude of low-frequency fluctuations (fALFFs), and Wavelet transform-based ALFFs (Wavelet-ALFFs) with standardization, percent amplitude of fluctuation (PerAF) with/without standardization were applied to evaluate the spontaneous brain activity of patients with DM1. Compared with HCs, patients with DM1 showed decreased ALFFs and Wavelet-ALFFs in the bilateral precuneus (PCUN), angular gyrus (ANG), inferior parietal, but supramarginal and angular gyri (IPL), posterior cingulate gyrus (PCG), superior frontal gyrus, medial (SFGmed), middle occipital gyrus (MOG), which were mainly distributed in the brain regions of default mode network (DMN). Decreased ALFFs and Wavelet-ALFFs were also seen in bilateral middle frontal gyrus (MFG), inferior frontal gyrus, opercular part (IFGoperc), which were the main components of the executive control network (ECN). Patients with DM1 also showed decreased fALFFs in SFGmed.R, the right anterior cingulate and paracingulate gyri (ACGR), bilateral MFG. Reduced PerAF in bilateral PCUN, ANG, PCG, MOG, and IPLL as well as decreased PerAF without standardization in PCUNR and bilateral PCG also existed in patients with DM1. In conclusion, patients with DM1 had decreased activity in DMN and ECN with increased fluctuations in the temporal cortex and cerebellum. Decreased brain activity in DMN was the most repeatable and reliable with PCUN and PCG being the most specific imaging biomarker of brain dysfunction in patients with DM1.

Intrinsic Brain Activity Alterations in Patients With Mild Cognitive Impairment-to-Normal Reversion: A Resting-State Functional Magnetic Resonance Imaging Study From Voxel to Whole-Brain Level.

Mild cognitive impairment (MCI) reversion refers to patients with MCI who revert from MCI to a normal cognitive state. Exploring the underlying neuromechanism of MCI reverters may contribute to providing new insights into the pathogenesis of Alzheimer's disease and developing therapeutic interventions. Information on patients with MCI and healthy controls (HCs) was collected from the Alzheimer's Disease Neuroimaging Initiative database. We redefined MCI reverters as patients with MCI whose logical memory scores changed from MCI to normal levels using the logical memory criteria. We explored intrinsic brain activity alterations in MCI reverters from voxel, regional, and whole-brain levels by comparing resting-state functional magnetic resonance imaging metrics of the amplitude of low-frequency of fluctuation (ALFF), the fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) between MCI reverters and HCs. Finally, partial correlation analyses were conducted between cognitive scale scores and resting-state functional magnetic resonance imaging metrics of brain regions, revealing significant group differences. Thirty-two patients with MCI from the Alzheimer's Disease Neuroimaging Initiative database were identified as reverters. Thirty-seven age-, sex-, and education-matched healthy individuals were also enrolled. At the voxel level, compared with the HCs, MCI reverters had increased ALFF, fALFF, and PerAF in the frontal gyrus (including the bilateral orbital inferior frontal gyrus and left middle frontal gyrus), increased PerAF in the left fusiform gyrus, and decreased ALFF and fALFF in the right inferior cerebellum. Regarding regional and whole-brain levels, MCI reverters showed increased ReHo in the left fusiform gyrus and right median cingulate and paracingulate gyri; increased DC in the left inferior temporal gyrus and left medial superior frontal; decreased DC in the right inferior cerebellum and bilateral insular gyrus relative to HCs. Furthermore, significant correlations were found between cognitive performance and neuroimaging changes. These findings suggest that MCI reverters show significant intrinsic brain activity changes compared with HCs, potentially related to the cognitive reversion of patients with MCI. These results enhance our understanding of the underlying neuromechanism of MCI reverters and may contribute to further exploration of Alzheimer's disease.

Active Ingredients and Mechanism of Action of Rhizoma Coptidis against Type 2 Diabetes Based on Network-Pharmacology and Bioinformatics.

A pharmacological network of "component/target/pathway" for Rhizoma coptidis against type 2 diabetes (T2D) was established by network-pharmacology, and the active components of Rhizoma coptidis and its mechanism were explored. A literature-based and database study of the components of Rhizoma coptidis was carried out and screened by ADME parameters. The targets of Rhizoma coptidis were predicted by the ligand similarity method. Related pathways were analyzed with databases, and software was used to construct a "component/target/path" network. The mechanism was further confirmed by GEO database with R software. A total of 12 active components were screened from Rhizoma coptidis, involving 57 targets including MAPK1, STAT3, INSR, and 38 signaling pathways were associated with T2D. Related signaling pathways included essential pathways for T2D such as insulin resistance, and pathways that had indirect effect on T2D. It was suggested that Rhizoma coptidis may exert its effects against T2D through multi-component, multi-target, and multi-pathway forms.

Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect.

Albiziae Flos (AF) has been experimentally proven to have an antidepressant effect. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of action of AF in depression has not been completely deciphered. This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF. The methods included collection and screening of chemical components, prediction of depression-associated targets of the active components, gene enrichment, and network construction and analysis. Quercetin and 4 other active components were found to exert antidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand-receptor interaction pathways. DRD2, HTR1A, and SLC6A4 were identified as important targets of the studied bioactive components of AF. This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.

A Novel Antiplatelet Aggregation Target of Justicidin B Obtained From Rostellularia Procumbens (L.) Nees.

The present study explored the possible bioactive ingredients and target protein of Rostellularia procumbens (L.) Nees. Firstly, we found that the ethyl acetate extraction obtained from R. procumbens could inhibit platelet aggregation. Then, gene chip was used to investigate differentially expressed genes and blood absorption compounds were investigated using high performance liquid chromatography-mass spectrometry characterization (LC-MS). Depending on the results of gene chip and LC-MS, the targets of blood absorption compounds were predicted according to the reverse pharmacophore matching model. The platelet aggregation-related genes were discovered in databases, and antiplatelet aggregation-related gene targets were selected through comparison. The functions of target genes and related pathways were analyzed and screened using the DAVID database, and the network was constructed using Cytoscape software. We found that integrin αIIbß3 had a highest degree, and it was almost the intersection of all pathways. Then, blood absorption compounds were screened by optical turbidimetry. Western blot (WB) revealed that justicidin B separated from the ethyl acetate fraction may inhibit the expression of integrin αIIbß3 protein. For the first time, we used Prometheus NT.48 and MST to detect the stability of this membrane protein to optimize the buffer and studied the interaction of justicidin B with its target protein. To our best knowledge, this is the first report to state that justicidin B targets the integrin αIIbß3 protein. We believe that our findings can provide a novel target protein for the further understanding of the mechanism of R. procumbens on platelet aggregation.

Hyaluronic Acid Nanoparticle Composite Films Confer Favorable Time-Dependent Biofunctions for Vascular Wound Healing.

Vascular stent implantation is the primary treatment for coronary artery disease. Surface modification of coronary stents is a topic of interest to prevent thrombosis and restenosis and to promote endothelization. However, bioactive coatings on implants have not yet been fully developed for the time-ordered biological requirements of vascular stents. The first month after vascular stent implantation, the pathological changes in the injured vascular tissue are complex and time-ordered. Therefore, vascular stents possess time-dependent biofunctions with early phase anticoagulant and anti-inflammatory properties. In the later stage, inhibitory effects on smooth muscle cell proliferation and the promotion of endothelial cell adhesion might meet the requirements of vascular repair. We fabricated three types of hyaluronic acid nanoparticles (HA-NPs) by subjecting HA and poly(ether imide) to ethyl(dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide coupling reaction. The HA-NPs prepared by HA with a molecular weight of 100 kDa showed the best stability in a hyaluronidase environment. HA-NP composite films (HA-NCFs) were then fabricated by coimmobilizing selected HA-NPs (100 kDa) and HA molecules (100 kDa) through amide reaction on PDA/HD coated 316 L stainless steel surfaces. The detachment behavior of HA-NPs (100 kDa) in PBS for 20 days indicated that the HA-NPs (100 kDa) gradually detached from the surface. In vitro tests (anticoagulant and anti-inflammatory tests, endothelial cells, and smooth muscle cells seeding, and bacterial adhesion test) indicated that the newly fabricated HA-NCFs have inhibitory effects on the adhesion of fibrinogen, platelets, macrophages, bacteria, SMCs, and ECs. As the HA-NPs detached from the surface, the HA-NCFs showed excellent gradual comprehensive biocompatibility, which promoted adhesion and proliferation of ECs while still exerting inhibitory effects on the platelets, macrophages, and SMCs. Finally, in vivo SS wire implantation test (aortic implantation in healthy Sprague-Dawley rats) showed that HA-NCFs possessed anti-inflammatory properties, inhibited the proliferation of smooth muscle cells, and promoted re-endothelialization. In particular, HA-NCFs with time-dependent biofunctions showed better antirestenosis effects than those of surfaces modified with molecular HA, which exhibited constant biocompatibility. This study provides an important basis for the construction of HA-NP composite films with favorable time-dependent biofunctions for the time-ordered biological requirements of vascular stent.

A Short Half-Life αIIbß3 Antagonist ANTP266 Reduces Thrombus Formation.

Integrin αIIbß3 plays a pivotal role in platelet aggregation. Three αIIbß3 antagonists have been approved by the Food and Drug Administration (FDA) for the treatment of cardiovascular diseases. Unfortunately, all of these three drugs can cause the side effect of severe bleeding. Therefore, developing a new αIIbß3 antagonist with low bleeding was needed. In the present study, we screened compounds by using a fibrinogen/integrin αIIbß3 enzyme-linked immunosorbent assay (ELISA), and a novel αIIbß3 antagonist ANTP266 was attained. The antithrombotic effects of ANTP266 were estimated by using two animal models, the bleeding risk was estimated by using a mice tail cutting assay, and the plasma half-life time was tested by LC-MS/MS. The results showed that ANTP266 potently decreased thrombosis formation, while not prolonging bleeding time at its effective dosage. The bleeding of ANTP266 reduced rapidly as time went on from 5 to 60 min, but tirofiban produced high bleeding continuously. The plasma half-life of ANTP266 in rats was 10.8 min. Taken together, ANTP266 is an effective antithrombotic agent with a low bleeding risk. The shorter bleeding time benefits from its short plasma half-life. ANTP266 could be a candidate for developing the αIIbß3 antagonist of rapid elimination for a patient undergoing percutaneous coronary intervention.

A new oleanolic-type triterpene glycoside from Anchusa italica.

A new oleanolic-type triterpene glycoside, (3ß,21ß)-21-[(ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranosyl)oxy]-3-hydroxyolean-12-en-28-oic acid (1), together with five analogues, oleanazuroside 1 (2), oleanazuroside 2 (3), 24-hydroxytormentic acid ester glucoside (4), 24-epi-pinfaensin (5), and oleanolic acid 3-O-α-l-arabinoside (6) were isolated from the n-butyl alcohol extract of Anchusa italica. Their structures were determined spectroscopically and compared with previously reported spectral data. Compounds 3-4 and 6 were evaluated for their cytotoxic activities against five human cancer cell lines, but only compound 6 showed moderate cytotoxicity.

Peritoneal dialysis for autosomal dominant polycystic kidney disease: a retrospective study.

To describe the long-term clinical outcomes of patients with autosomal dominant polycystic kidney disease (ADPKD) who are on peritoneal dialysis (PD) therapy. We performed a retrospective matched-cohort analysis comparing the clinical outcomes of 30 ADPKD patients with those of 30 non-diabetic patients who had bilateral small kidneys between July 1 2007 and July 31 2014. The patient groups were matched by age, gender, and time of PD initiation. There were no significant differences in the demographic or biochemical parameters, comorbid conditions, residual glomerular filtration rate, or Charlson comorbidity score at the beginning of PD. The median renal volume was 1315 ml for the ADPKD group and 213 ml for the control group. Patients with ADPKD had similar 3-year patient survival (90.6% versus 86.3%, P=0.807) and technique survival (89.2% versus 74.3%, P=0.506) compared with non-ADPKD patients. Also, there was no significant difference in the peritonitis-free survival between the ADPKD and control groups (P=0.22), and rates of peritonitis were similar (0.19 versus 0.21 episodes per patient-year, P=0.26). No differences were observed in the incidence of PD-related complications, such as hernia and dialysate leak. ADPKD is not a contraindication for PD, and a subgroup of ADPKD patients with relatively small kidney volume can be treated using PD.