Circular RNA circWNK1 inhibits the progression of gastric cancer via regulating the miR-21-3p/SMAD7 axis.

Gastric cancer (GC) is a highly aggressive malignancy with limited treatment options for advanced-stage patients. Recent studies have highlighted the role of circular RNA (circRNA) as a novel regulator of cancer progression in various malignancies. However, the underlying mechanisms by which circRNA contributes to the development and progression of GC remain poorly understood. In this study, we utilized microarrays and real-time quantitative polymerase chain reaction (qRT-PCR) to identify and validate a downregulated circRNA, hsa_circ_0003251 (referred to as circWNK1), in paired GC and normal tissues. Through a series of in vitro and in vivo gain-of-function and loss-of-function assays, we demonstrated that circWNK1 exerts inhibitory effects on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of GC cells. Additionally, we discovered that circWNK1 acts as a competitive endogenous RNA (ceRNA) for SMAD7 by sequestering miR-21-3p. Our findings were supported by comprehensive biological information analysis, as well as RNA pull-down, luciferase reporter gene, and western blot assays. Notably, the downregulation of circWNK1 in GC cells resulted in reduced SMAD7 expression, subsequently activating the TGF-ß signaling pathway. Collectively, our study reveals that circWNK1 functions as a tumor suppressor in GC by regulating the miR-21-3p/SMAD7-mediated TGF-ß signaling pathway. Furthermore, circWNK1 holds promise as a potential biomarker for the diagnosis and treatment of GC.

Auto-inducible synthetic pathway in E. coli enhanced sustainable indigo production from glucose.

Indigo is widely used in textile industries for denim garments dyeing and is mainly produced by chemical synthesis which, however, raises environmental sustainability issues. Bio-indigo may be produced by fermentation of metabolically engineering bacteria, but current methods are economically incompetent due to low titer and the need for an inducer. To address these problems, we first characterized several synthetic promoters in E. coli and demonstrated the feasibility of inducer-free indigo production from tryptophan using the inducer-free promoter. We next coupled the tryptophan-to-indigo and glucose-to-tryptophan pathways to generate a de novo glucose-to-indigo pathway. By rational design and combinatorial screening, we identified the optimal promoter-gene combinations, which underscored the importance of promoter choice and expression levels of pathway genes. We thus created a new E. coli strain that exploited an indole pathway to enhance the indigo titer to 123 mg/L. We further assessed a panel of heterologous tryptophan synthase homologs and identified a plant indole lyase (TaIGL), which along with modified pathway design, improved the indigo titer to 235 mg/L while reducing the tryptophan byproduct accumulation. The optimal E. coli strain expressed 8 genes essential for rewiring carbon flux from glucose to indole and then to indigo: mFMO, ppsA, tktA, trpD, trpC, TaIGL and feedback-resistant aroG and trpE. Fed-batch fermentation in a 3-L bioreactor with glucose feeding further increased the indigo titer (≈965 mg/L) and total quantity (≈2183 mg) at 72 h. This new synthetic glucose-to-indigo pathway enables high-titer indigo production without the need of inducer and holds promise for bio-indigo production.

Development of a Preoperative Screening Tool to Reduce Morbidity and Mortality of COVID-19-positive Hepatobiliary Patients.

PURPOSE: This study aimed to create a preoperative risk assessment form for COVID-19-positive hepatobiliary patients to guide further prevention of complications after surgery and reduce morbidity and mortality. DESIGN: Based on the literature, focus groups, and case studies, a multidisciplinary panel of 15 experts conducted three rounds of a Delphi study that resulted in the development of a preoperative risk assessment form to be used by healthcare professionals in the treatment of COVID-19-positive hepatobiliary patients. METHODS: A preoperative risk assessment form for health professionals to use among COVID-19-positive hepatobiliary patients was developed based on literature, focus groups, and case studies. A 3-round Delphi study was conducted to validate and revise the risk assessment form using a multidisciplinary panel of 15 experts involved in hepatobiliary surgery. FINDINGS: The experts demonstrated high cooperation and familiarity with the research topic, with positive coefficients ranging from 93.33% to 100% and authority coefficients ranging from 0.83 to 0.86. The coordination coefficients were 0.33, 0.26, and 0.22, respectively, indicating good coordination among expert opinions. The final risk assessment form included 9 primary (first-level) indicators, 38 secondary (second-level) indicators, and 122 tertiary (third-level) indicators. CONCLUSIONS: The preoperative risk assessment form for hepatobiliary surgery patients infected with COVID-19 is scientifically rigorous, reliable, and valid. This screening tool may be used by health providers to identify high-risk patients, prevent postoperative complications, and reduce morbidity and mortality.

Efficient Homolytic Cleavage of H2O2 on Hydroxyl-Enriched Spinel CuFe2O4 with Dual Lewis Acid Sites.

Traditional H2O2 cleavage mediated by macroscopic electron transfer (MET) not only has low utilization of H2O2, but also sacrifices the stability of catalysts. We present a non-redox hydroxyl-enriched spinel (CuFe2O4) catalyst with dual Lewis acid sites to realize the homolytic cleavage of H2O2. The results of systematic experiments, in situ characterizations, and theoretical calculations confirm that tetrahedral Cu sites with optimal Lewis acidity and strong electron delocalization can synergistically elongate the O-O bonds (1.47 Š→ 1.87 Å) in collaboration with adjacent bridging hydroxyl (another Lewis acid site). As a result, the free energy of H2O2 homolytic cleavage is decreased (1.28 eV → 0.98 eV). H2O2 can be efficiently split into ⋅OH induced by hydroxyl-enriched CuFe2O4 without MET, which greatly improves the catalyst stability and the H2O2 utilization (65.2 %, nearly 2 times than traditional catalysts). The system assembled with hydroxyl-enriched CuFe2O4 and H2O2 affords exceptional performance for organic pollutant elimination. The scale-up experiment using a continuous flow reactor realizes long-term stability (up to 600 mL), confirming the tremendous potential of hydroxyl-enriched CuFe2O4 for practical applications.

Biomineralized tetramethylpyrazine-loaded PCL/gelatin nanofibrous membrane promotes vascularization and bone regeneration of rat cranium defects.

Conventional electrospinning produces nanofibers with smooth surfaces that limit biomineralization ability. To overcome this disadvantage, we fabricated a tetramethylpyrazine (TMP)-loaded matrix-mimicking biomineralization in PCL/Gelatin composite electrospun membranes with bubble-shaped nanofibrous structures. PCL/Gelatin membranes (PG), PCL/Gelatin membranes containing biomineralized hydroxyapatite (HA) (PGH), and PCL/Gelatin membranes containing biomineralized HA and loaded TMP (PGHT) were tested. In vitro results indicated that the bubble-shaped nanofibrous surface increased the surface roughness of the nanofibers and promoted mineralization. Furthermore, sustained-release TMP had an excellent drug release efficiency. Initially released vigorously, it reached stabilization at day 7, and the slow-release rate stabilized at 61.0 ± 1.8% at 28 days. All membranes revealed an intact cytoskeleton, cell viability, and superior adhesion and proliferation when stained with Ghost Pen Cyclic Peptide, CCK-8, cell adhesion, and EdU. In PGHT membranes, the osteogenic and vascularized gene expression of BMSCs and human vascular endothelial cells was significantly upregulated compared with that in other groups, indicating the PGHT membranes exhibited an effective vascularization role. Subsequently, the membranes were implanted in a rat cranium defect model for 4 and 8 weeks. Micro-CT and histological analysis results showed that the PGHT membranes had better bone regenerative patterns. Additionally, the levels of CD31 and VEGF significantly increased in the PGHT membrane compared with those in other membranes. Thus, PGHT membranes could accelerate the repair of cranium defects in vivo via HA and TMP synergistic effects.

Our experience with propranolol for infantile hemangioma.

BACKGROUND/OBJECTIVES: The most frequent benign vascular tumor in children is infantile hemangioma (IH). For severe IHs, propranolol has become the first-line Treatment. Despite the fact that several studies have comprehensive therapy regimens, including the best time to start Treatment, dosage, visit frequency, and treatment duration, there is still controversy about the best time to start and stop propranolol medication. METHODS: Between January 2016 and February 2019, dermatologists experienced hemangioma treatment and recommended propranolol treatment for 232 IHs. A total of 90 patients completed the treatment process after undergoing a color Doppler ultrasound test. RESULTS: Propranolol uniquely affects each IH. Ninety patients were divided into two groups in this study: entire regression (n = 40) and partial regression (n = 50). The entire regression group's initial treatment period (4.3 ± 2.97 months) was substantially shorter than the partial regression group's (5.2 ± 4.57 months) (p < 0.05). Between the entire regression group (23.4 ± 12.8 months) and the partial regression group (24.5 ± 16.6 months), there was no significant difference in time to reduce propranolol. The partial regression group (32.9 ± 25.3month) had a lengthier treatment course than the entire regression group (23.4 ± 13.7 months) (p < 0.05). The partial regression group (22%), like the entire regression group, had a higher recurrence rate (5%). The overall proportion of hemangiomas on the face (particularly periocular hemangioma) in the regression group was greater than in the control group. CONCLUSION: The entire regression group's initial treatment time was significantly shorter than the partial regression group's. As a result, as soon as a hemangioma is discovered, it should be treated. To determine the appropriate time to reduce propranolol, we must evaluate the patient's age and the percentage of tumor regression. Periocular hemangioma may have a better prognosis than other types. Given the small number of patients in our study, we will need to do more research in the future to confirm our findings.

Construction and validation of the Racially Biased Reasoning Scale: A measure of beliefs about police interactions with people of color.

OBJECTIVES: The purpose of this study was to develop and provide initial psychometric support for the Racially Biased Reasoning Scale-Police (RBias-Police). The vignette-based RBias-Police is designed to capture rigid racially biased beliefs. The items focus on police interactions with people of color as this is a particularly emotional-laden issue in the United States that signifies deeper racial and social intolerance. METHOD: Data from a combined sample of 1,156 participants were collected through Mechanical Turk for two interrelated studies. In the first study, we used matrix sampling and exploratory structural equation modeling to explore the factor structure of RBias-Police. In the second study, we conducted confirmatory factor analysis and explored the construct validity with theoretically relevant concepts. RESULTS: In Study 1, we found that 10 items with three factors solution captured the data across each of the six vignettes: (a) Minimization of Racism, (b) Target Apathy, and (c) Target Blaming. In Study 2, findings from confirmatory factor analysis supported that the three-factor model was a good fit to the data. The RBias-Police factors were positively related to color-blind racial ideology and the general belief in a just world in theoretically expected ways. CONCLUSIONS: Across two studies, our findings provide initial psychometric support for the RBias-Police; this new measure captures both affective and cognitive dimensions of biased reasoning. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Phenotypes of atopic dermatitis and the risk for subsequent asthma: A systematic review and meta-analysis.

BACKGROUND: Various atopic dermatitis (AD) phenotypes showed an enormously heterogenic risk for subsequent asthma development. OBJECTIVE: We aimed to investigate the association between AD phenotypes and the risk for progression to asthma. METHODS: We searched PubMed, Embase, and Web of Science databases for relevant publications. Pooled relative risks (RR) with 95% CI were calculated using the CMA-3.0 software. This study has been registered with PROSPERO (CRD42019129273). RESULTS: We analyzed 39 publications with 458,810 participants. The RR for asthma in AD was 2.16 (95% CI, 1.88-2.48). The risk in persistent AD (RR, 3.36; 95% CI, 2.83-3.99) was higher than in transient AD (RR, 1.52; 95% CI, 1.34-1.73), and the risk in severe AD (RR, 2.40; 95% CI, 1.96-2.94) was higher than in mild AD (RR, 1.82; 95% CI, 1.03-3.23) or moderate AD (RR, 1.51; 95% CI, 1.30-1.75). The risk for asthma in early-onset AD was slightly higher than in late-onset AD and higher in boys than in girls. LIMITATIONS: The AD and asthma definitions differed across the included studies. CONCLUSION: Patients with persistent or severe AD were at a higher risk for developing asthma. These findings further elucidate the atopic march and identify target populations for asthma prevention.

Polarization of macrophages in the trigeminal ganglion of rats with pulpitis.

BACKGROUND: Dental pulp tissues are rich in pain-related afferent nerve fibers, which originate from primary sensory neurons in the trigeminal ganglion (TG). The mechanisms of central nervous system (CNS) underlying ectopic pain following peripheral inflammation have been reported that the macrophages as inflammatory and immunologic mediators in the TG play an important role in the process of pulpitis and hyperalgesia. OBJECTIVE(S): To observe the polarization response and dynamic distribution of macrophages in the TG during the development of dental pulp inflammation. METHODS: A rat model of pulpitis was established using complete Freund's adjuvant (CFA). Hematoxylin-eosin (HE), immunohistochemistry (IHC), immunofluorescence (IF), toluidine blue (TB) staining, and RT-qPCR were performed to observe the expression of macrophage-related factors in the TG. RESULTS: The results of IHC staining showed that M2 macrophages labeled with CD206 were observed in the TG of both the control and CFA groups. The statistical analysis indicated that the number of CD206-positive macrophages in the TG increased significantly at 24 h after CFA-induced pulpitis, reached a peak at 2 weeks, and then returned to the normal level after 6 weeks. The ratio of M2/M1 in the CFA groups was significantly lower than that in the control group from 24 to 72 h, and this pattern was reversed at 2 weeks after CFA-induced pulpitis; then, the ratio increased significantly and was maintained at a high level for 4 weeks. RT-qPCR results showed that the expression of IL-10 in the TG increased significantly from 1 to 4 weeks after CFA-induced pulpitis. CONCLUSION: The trend of M2 macrophages was opposite to that of M1 macrophages in the TG during the process of pulpitis induced by CFA, which is consistent with the expression of macrophage-related cytokines. Macrophage polarization in the TG may participate in the neuroinflammation response induced by dental pulpitis.

Acoustic evolution of old Italian violins from Amati to Stradivari.

The shape and design of the modern violin are largely influenced by two makers from Cremona, Italy: The instrument was invented by Andrea Amati and then improved by Antonio Stradivari. Although the construction methods of Amati and Stradivari have been carefully examined, the underlying acoustic qualities which contribute to their popularity are little understood. According to Geminiani, a Baroque violinist, the ideal violin tone should "rival the most perfect human voice." To investigate whether Amati and Stradivari violins produce voice-like features, we recorded the scales of 15 antique Italian violins as well as male and female singers. The frequency response curves are similar between the Andrea Amati violin and human singers, up to ∼4.2 kHz. By linear predictive coding analyses, the first two formants of the Amati exhibit vowel-like qualities (F1/F2 = 503/1,583 Hz), mapping to the central region on the vowel diagram. Its third and fourth formants (F3/F4 = 2,602/3,731 Hz) resemble those produced by male singers. Using F1 to F4 values to estimate the corresponding vocal tract length, we observed that antique Italian violins generally resemble basses/baritones, but Stradivari violins are closer to tenors/altos. Furthermore, the vowel qualities of Stradivari violins show reduced backness and height. The unique formant properties displayed by Stradivari violins may represent the acoustic correlate of their distinctive brilliance perceived by musicians. Our data demonstrate that the pioneering designs of Cremonese violins exhibit voice-like qualities in their acoustic output.

Materials Engineering of Violin Soundboards by Stradivari and Guarneri.

We investigated the material properties of Cremonese soundboards using a wide range of spectroscopic, microscopic, and chemical techniques. We found similar types of spruce in Cremonese soundboards as in modern instruments, but Cremonese spruces exhibit unnatural elemental compositions and oxidation patterns that suggest artificial manipulation. Combining analytical data and historical information, we may deduce the minerals being added and their potential functions-borax and metal sulfates for fungal suppression, table salt for moisture control, alum for molecular crosslinking, and potash or quicklime for alkaline treatment. The overall purpose may have been wood preservation or acoustic tuning. Hemicellulose fragmentation and altered cellulose nanostructures are observed in heavily treated Stradivari specimens, which show diminished second-harmonic generation signals. Guarneri's practice of crosslinking wood fibers via aluminum coordination may also affect mechanical and acoustic properties. Our data suggest that old masters undertook materials engineering experiments to produce soundboards with unique properties.

Precision diagnosis and therapy of a case of brain abscesses associated with asymptomatic pulmonary arteriovenous fistulas.

BACKGROUND: Brain abscesses, a severe infectious disease of the CNS, are usually caused by a variety of different pathogens, which include Streptococcus intermedius (S. intermedius). Pulmonary arteriovenous fistulas (PAVFs), characterized by abnormal direct communication between pulmonary artery and vein, are a rare underlying cause of brain abscesses. CASE PRESENTATION: The patient was a previous healthy 55-year-old man who presented with 5 days of headache and fever. Cerebral magnetic resonance imaging (MRI) suggested a brain abscess. Thoracic CT scan and angiography demonstrated PAVFs. Aiding by metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid (CSF) sample which identified S. intermedius as the causative pathogen, the patient was switched to the single therapy of large dose of penicillin G and was cured precisely and economically. CONCLUSIONS: It is an alternative way to perform mNGS to identify causative pathogens in patients with brain abscesses especially when the results of traditional bacterial culture were negative. Further thoracic CT or pulmonary angiography should also be undertaken to rule out PAVFs as the potential cause of brain abscess if the patient without any known premorbid history.

Laser ultrasonic imaging for defect detection on metal additive manufacturing components with rough surfaces.

Defects or discontinuities are inevitable during the melting and consolidation process of metal additive manufacturing. Online inspection of microdefects during the processing of layer-by-layer fusion is urgently needed for quality control. In this study, the laser ultrasonic C-scan imaging system is established to detect the surface defects of selective laser melting (SLM) samples that have a different surface roughness. An autosizing method based on the maximum correlation coefficient and lag time is proposed to accurately measure the defect length. The influences of the surface roughness on the laser ultrasound signal-to-noise ratio distribution and defect sizing accuracy are also studied. The results indicate that the proposed system can detect notches with a depth of 50 µm and holes with a diameter of 50 µm, comparable in size to raw powder particles. The average error for the length measurement can reach 1.5% if the notch is larger than 2 mm. Meanwhile, the sizing error of a 1 mm length notch is about 9%. In addition, there is no need to remove the rough surface of the as-built SLM samples during the detection process. Hence, we propose that the laser ultrasonic imaging system is a potential method for online inspection of metal additive manufacturing.

Chemical distinctions between Stradivari's maple and modern tonewood.

Violins made by Antonio Stradivari are renowned for having been the preferred instruments of many leading violinists for over two centuries. There have been long-standing questions about whether wood used by Stradivari possessed unique properties compared with modern tonewood for violin making. Analyses of maple samples removed from four Stradivari and a Guarneri instrument revealed highly distinct organic and inorganic compositions compared with modern maples. By solid-state 13C NMR spectroscopy, we observed that about one-third of hemicellulose had decomposed after three centuries, accompanied by signs of lignin oxidation. No apparent changes in cellulose were detected by NMR and synchrotron X-ray diffraction. By thermogravimetric analysis, historical maples exhibited reduced equilibrium moisture content. In differential scanning calorimetry measurements, only maples from Stradivari violins, but not his cellos, exhibited unusual thermooxidation patterns distinct from natural wood. Elemental analyses by inductively coupled plasma mass spectrometry suggested that Stradivari's maples were treated with complex mineral preservatives containing Al, Ca, Cu, Na, K, and Zn. This type of chemical seasoning was an unusual practice, unknown to later generations of violin makers. In their current state, maples in Stradivari violins have very different chemical properties compared with their modern counterparts, likely due to the combined effects of aging, chemical treatments, and vibrations. These findings may inspire further chemical experimentation with tonewood processing for instrument making in the 21st century.

Knockdown of XB130 restrains cancer stem cell-like phenotype through inhibition of Wnt/ß-Catenin signaling in breast cancer.

The cancer stem cells (CSCs) is a subset of cancer cells that possess stem cell properties, which plays a crucial role in the occurrence, metastasis, and recurrence of the tumor. XB130 is a novel adapter protein potentially serves as a functional factor in CSCs. To determine the role of CSCs in breast cancer, we focused on the study of XB130. In our study, we found that XB130 expression was significantly upregulated in breast cancer and was closely related to the clinicopathologic characteristics, overall survival and poor prognosis of breast cancer patients. Functionally, we found that knockdown of XB130 was not only played an important role in proliferation, epithelial-mesenchymal transition (EMT), and metastasis in breast cancer cells but also exhibited potent antitumor activity in animal tumor models. Moreover, we demonstrated that silencing endogenous XB130 regulated the cancer stem cell-like properties of breast cancer, including the formation of self-renewing spheres and the proportion of breast cancer SP+ cells. Mechanistically, our studies indicated that downregulation of XB130 restrained the EMT and Wnt/ß-catenin signaling, so as to weaken the tumor-initiating cell-like phenotype of breast cancer cells. This study indicates that XB130 plays an important role in maintaining the EMT and stem cell-like characteristics of breast cancer cells, supporting the significance of XB130 as a new potential therapeutic target for early diagnosis and prognosis of breast cancer.

Immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a PRISMA systematic review and meta-analysis.

BACKGROUND: Programmed cell death protein-1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have remarkable clinical efficacy in the treatment of non-small cell lung cancer (NSCLC); however, the breakdown of immune escape causes a variety of immune-related adverse events (irAEs). With the increasing use of PD-1/PD-L1 inhibitors alone or in combination with other therapies, awareness and management of irAEs have become more important. We aimed to assess the incidence and nature of irAEs associated with PD-1 and PD-L1 inhibitors for NSCLC. METHODS: Articles from the MEDLINE, EMBASE, and Cochrane databases were searched through December 2017. The incidence of overall and organ-specific irAEs was investigated in all clinical trials with nivolumab, pembrolizumab, atezolimumab, durvalumab, and avelumab as single agents for treatment of NSCLC. We calculated the pooled incidence using R software with package Meta. RESULTS: Sixteen trials were included in the meta-analysis: 10 trials with PD-1 inhibitors (3734 patients) and 6 trials with PD-L1 inhibitors (2474 patients). The overall incidence of irAEs was 22% (95% confidence interval [CI], 17-28) for all grades and 4% (95% CI, 2-6) for high-grade irAEs. The frequency of irAEs varied based on drug type and organ, and patients treated with PD-1 inhibitors had an increased rate of any grade and high-grade irAEs compared with patients who received PD-L1 inhibitors. Organ-specific irAEs were most frequently observed in, in decreasing order, the endocrine system, skin, pulmonary tract, and gastrointestinal tract. The total number of patients whose death was attributed to irAEs was 14 (0.34%), and most (79%) of these patients died because of pneumonitis. The median time to the onset of irAEs after the initiation of treatment was 10 weeks (interquartile range, 6-19.5 weeks) and varied depending on the organ system involved. CONCLUSIONS: The specificity of irAEs was closely associated with the mechanism of PD-1/PD-L1 antibodies involved in restarting anticancer immune attacks. Comprehensive understanding, timely detection, and effective management could improve the compliance of patients and guide the interruption of treatment.

Tripartite motif-containing 37 (TRIM37) promotes the aggressiveness of non-small-cell lung cancer cells by activating the NF-κB pathway.

Non-small-cell lung cancer (NSCLC), in which the NF-κB pathway is constitutively activated, is one of the most common malignancies. Herein, we identify an E3 ubiquitin ligase, tripartite motif-containing 37 (TRIM37), participating in the K63 polyubiquitination of TRAF2, which is a significant step in the activation of NF-κB signaling. Both the mRNA and the protein expression levels of TRIM37 were much higher in NSCLC cell lines and tissues than in normal bronchial epithelial cells and matched adjacent non-tumor tissues. TRIM37 expression correlated closely with clinical stage and poor survival in NSCLC. Overexpression of TRIM37 antagonized cisplatin-induced apoptosis, induced angiogenesis and proliferation, and increased the aggressiveness of NSCLC cells in vitro and in vivo, whereas inhibition of TRIM37 led to the opposite effects. Gene set enrichment analysis (GSEA) showed that TRIM37 expression significantly correlated with NF-κB signaling. Furthermore, we found that TRIM37 bound to TRAF2 and promoted K63-linked ubiquitination of TRAF2, sustaining the eventual activation of the NF-κB pathway. Mutation in the ring finger domain of TRIM37, a hallmark of E3 ubiquitin ligases, led to loss of the ability to promote K63 polyubiquitination of TRAF2 and activate NF-κB signaling. Taken together, our findings provide evidence that TRIM37 plays an important role in constitutive NF-κB pathway activation and could serve as a prognostic factor and therapeutic target in NSCLC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[Network pharmacological study of Schizonepetae Herba and Saposhnikoviae Radix in treatment of ulcerative colitis].

The aim of this paper was to screen the active targets of Schizonepetae Herba and Saposhnikoviae Radix in the treatment of ulcerative colitis by means of network pharmacology,and to investigate their mechanism of action. The effective components of Schizonepetae Herba and Saposhnikoviae Radix were screened out by traditional Chinese medicine systematic pharmacological( TCMSP)database,with oral bioavilability( OB) ≥30% and drug-like( DL) ≥18% selected as the thresholds. Target PPI network was built between the main components and their corresponding targets. One hundred and eighty-two human genes corresponding to the medicine target sites were obtained from Uniprot database; 3 874 genes corresponding to ulcerative colitis were obtained from Genecard database.A total of 115 intersection genes were screened from disease genes and medicine genes,and the PPI interaction analysis was conducted by using String tool. Disease-target PPI network was drawn by using Cytoscape software,and component-target-disease network was constructed. One hundred and eight nodes and 1 882 connections were found,and then Cytoscape software was used to merge the networks and filter the core network for gene GO function analysis and KEGG pathway enrichment analysis. The mechanism of Schizonepetae Herba and Saposhnikoviae Radix was then verified by animal experiment. Gene GO functional analysis suggested that biological process,molecular functions and cell components were involved,and it was found that ulcerative colitis might be related to transcription factor activity,and cytokine receptor binding,etc. Gene KEGG pathway enrichment analysis showed that the mechanism of ulcerative colitis might be associated with TNF and Toll-like receptors( TLRs) signaling pathway-mediated cytoinflammatory factors interleukin-1( IL-1) and interleukin-6( IL6). The possible mechanism of the effective components of Schizonepetae Herba and Saposhnikoviae Radix in treating ulcerative colitis might be related to intervening the cytokine receptor binding of TNF and TLRs signaling pathways,reducing the transcription of nuclear factor-kappaB( NF-κB),and inhibiting the secretion of intestinal inflammatory factors IL-1 and IL-6.

Angiopoietin-like protein 8 in early pregnancy improves the prediction of gestational diabetes.

AIMS/HYPOTHESIS: Screening high-risk individuals for gestational diabetes mellitus (GDM) in early pregnancy conventionally relies on established maternal risk factors; however, the sensitivity and specificity of these factors are not satisfactory. The present study aimed to determine whether the concentration of angiopoietin-like protein 8 (ANGPTL8), either alone or combined with other risk factors in early pregnancy, could be used to predict subsequent GDM. METHODS: From August 2015 to January 2016, 474 women receiving prenatal care at around 12-16 weeks of gestation were recruited into the study. ANGPTL8 levels were measured at the first prenatal visit. All the participants received a 75 g OGTT during weeks 24-28 of gestation. RESULTS: ANGPTL8 levels in early pregnancy were considerably higher in women who developed GDM than those who maintained normal glucose tolerance (2822 ± 938 vs 2120 ± 1118 pg/ml, respectively; p < 0.0001). Multivariable logistic regression revealed that ANGPTL8 levels were significantly associated with risk of GDM independent of conventional risk factors. In addition, women in the highest quartile of ANGPTL8 concentration had an 8.75-fold higher risk of developing GDM compared with women in the lowest quartile (OR8.75, 95%CI 2.43, 31.58). More importantly, incorporating ANGPTL8 into the conventional prediction model significantly increased the AUC for prediction of GDM (0.772vs 0.725; p = 0.019). CONCLUSIONS: Our study suggests that ANGPTL8 levels in early pregnancy are significantly and independently associated with risk of GDM at 24-28 weeks of gestation. Combining ANGPTL8 levels with conventional risk factors could thus improve the prediction of GDM.