Assessing Diagnostic Performance Using the Transverse Plane Plus Coronal Plane Compared With the Transverse Plane Alone in Screening Automated Breast Ultrasound.

OBJECTIVES: The coronal plane is the unique display mode of automated breast (AB) ultrasound (US), which has valuable features of showing the entire breast anatomy and providing additional diagnostic value for breast lesions. However, whether adding the coronal plane could improve the diagnostic performance in screening breast cancer remains uncertain. This study aimed to evaluate the value of adding the coronal plane in interpretation for AB US screening. METHODS: In this retrospective study, AB US images from 644 women (396 in the no-finding group, 143 with benign lesions, and 105 with malignant lesions) aged 40-70 years were collected between January 2016 and October 2020. Four novice radiologists (with 1-5 years of experience with breast US) and four experienced radiologists (with >5 years of experience with breast US) were assigned to read all AB US images in the transverse plane plus coronal plane (T + C planes) and transverse plane (T plane) alone in separate reading sessions. Diagnostic performance, lesion conspicuity, and reading time were compared using analysis of variance. RESULTS: The mean reading time of all radiologists was significantly shorter in the T + C planes reading mode than in the T plane alone (115 ± 32 vs 128 ± 31 s, respectively; P < .05), and cancers had a higher conspicuity (odds ratio, 1.76; 95% confidence interval [CI], 1.00-3.08; P = .04). No significant differences were noted in the two reading modes (T + C planes vs T plane) in the sensitivity (82% [95% CI, 74-89%] vs 81% [95% CI, 74-88%], respectively; P = .68) and specificity (68% [95% CI, 62-75%] vs 70% [95% CI, 64-75%], respectively; P = .39) when Breast Imaging-Reporting and Data System (BI-RADS) 3 was set as the threshold. There were also no significant differences in the two reading modes (T + C planes vs T plane) in the sensitivity (70% [95% CI, 64-76%] vs 69% [95% CI, 63-75%], respectively; P = .39) and specificity (91% [95% CI, 87-96%] vs 91% [95% CI, 88-95%], respectively; P = .90) when BI-RADS 4 was set as the threshold. In addition, the mean areas under the receiver operating characteristic curves of all radiologists in the two reading modes (T + C planes vs T plane) were not significantly different (0.84 [95% CI, 0.79-0.89] vs 0.83 [95% CI, 0.78-0.89], respectively; P = .61). CONCLUSIONS: Adding a coronal plane in the AB US screening setting saved the reading time and improved the conspicuity of breast cancers but not the diagnostic performance.

Evaluation of the anti-viral efficacy of three different dsRNA nanoparticles against potato virus Y using various delivery methods.

Nanoparticles (NPs) derived from RNA interference (RNAi) are considered a potentially revolutionary technique in the field of plant protection in the future. However, the application of NPs in RNAi is hindered by the conflict between the high cost of RNA production and the large quantity of materials required for field application. This study aimed to evaluate the antiviral efficacy of commercially available nanomaterials, such as chitosan quaternary ammonium salt (CQAS), amine functionalized silica nano powder (ASNP), and carbon quantum dots (CQD), that carried double-stranded RNA (dsRNA) via various delivery methods, including infiltration, spraying, and root soaking. ASNP-dsRNA NPs are recommended for root soaking, which is considered the most effective method of antiviral compound application. The most effective antiviral compound tested was CQAS-dsRNA NPs delivered by root soaking. Using fluorescence, FITC-CQAS-dsCP-Cy3, and CQD-dsCP-Cy3 NPs demonstrated the uptake and transport pathways of dsRNA NPs in plants when applied to plants in different modes. The duration of protection with NPs applied in various modes was then compared, providing references for evaluating the retention period of various types of NPs. All three types of NPs effectively silenced genes in plants and afforded at least 14 days of protection against viral infection. Particularly, CQD-dsRNA NPs could protect systemic leaves for 21 days following spraying.

NbMLP43 Ubiquitination and Proteasomal Degradation via the Light Responsive Factor NbBBX24 to Promote Viral Infection.

The ubiquitin-proteasome system (UPS) plays an important role in virus-host interactions. However, the mechanism by which the UPS is involved in innate immunity remains unclear. In this study, we identified a novel major latex protein-like protein 43 (NbMLP43) that conferred resistance to Nicotiana benthamiana against potato virus Y (PVY) infection. PVY infection strongly induced NbMLP43 transcription but decreased NbMLP43 at the protein level. We verified that B-box zinc finger protein 24 (NbBBX24) interacted directly with NbMLP43 and that NbBBX24, a light responsive factor, acted as an essential intermediate component targeting NbMLP43 for its ubiquitination and degradation via the UPS. PVY, tobacco mosaic virus, (TMV) and cucumber mosaic virus (CMV) infections could promote NbMLP43 ubiquitination and proteasomal degradation to enhance viral infection. Ubiquitination occurred at lysine 38 (K38) within NbMLP43, and non-ubiquitinated NbMLP43(K38R) conferred stronger resistance to RNA viruses. Overall, our results indicate that the novel NbMLP43 protein is a target of the UPS in the competition between defense and viral anti-defense and enriches existing theoretical studies on the use of UPS by viruses to promote infection.

Unraveling the regulatory network of miRNA expression in Potato Y virus-infected of Nicotiana benthamiana using integrated small RNA and transcriptome sequencing.

Potato virus Y (PVY) disease is a global problem that causes significant damage to crop quality and yield. As traditional chemical control methods are ineffective against PVY, it is crucial to explore new control strategies. MicroRNAs (miRNAs) play a crucial role in plant and animal defense responses to biotic and abiotic stresses. These endogenous miRNAs act as a link between antiviral gene pathways and host immunity. Several miRNAs target plant immune genes and are involved in the virus infection process. In this study, we conducted small RNA sequencing and transcriptome sequencing on healthy and PVY-infected N. benthamiana tissues (roots, stems, and leaves). Through bioinformatics analysis, we predicted potential targets of differentially expressed miRNAs using the N. benthamiana reference genome and the PVY genome. We then compared the identified differentially expressed mRNAs with the predicted target genes to uncover the complex relationships between miRNAs and their targets. This study successfully constructed a miRNA-mRNA network through the joint analysis of Small RNA sequencing and transcriptome sequencing, which unveiled potential miRNA targets and identified potential binding sites of miRNAs on the PVY genome. This miRNA-mRNA regulatory network suggests the involvement of miRNAs in the virus infection process.

Assessment of Neoadjuvant Treatment Response Using Automated Breast Ultrasound in Breast Cancer.

Breast imaging techniques are used to assess the tumor response to neoadjuvant treatment (NAT), which is increasingly one of the preferred therapeutic options and increases the rate of breast conservation for breast cancer. Herein, we report a case in which a woman was diagnosed with invasive ductal carcinoma in the left breast and received NAT before surgery. Automated breast ultrasound (AB US) was regularly performed before and during the NAT to evaluate the tumor response to NAT by measuring diameter changes and volume reductions of the tumor. Images showed that the tumor size was significantly reduced and disappeared after 7 cycles of NAT, except for macrocalcification. Postoperative histopathological examination confirmed that there were no residual tumor cells. We found that AB US overcame the limitations of handheld US, such as operator dependence, poor reproducibility and limited field of view, and can be an alternative modality to assess the tumor response of NAT in the absence of magnetic resonance imaging (MRI) instruments.

Compatibility and stability of methylprednisolone sodium succinate and granisetron hydrochloride in 0.9% sodium chloride solution.

A combination of methylprednisolone sodium succinate (MSS) and granisetron hydrochloride (GH) is generally devoted to treating the chemotherapy-induced nausea and vomiting. To date, none of these novel mixtures have been commercially available. The present study was aimed at investigating physical and chemical compatibility and stability of a combination of MSS with GH in 0.9% sodium chloride injection for 72 hours at 4°C and 25°C. A mixture of MSS (0.4-0.8 mg/mL) with GH (0.03 mg/mL) was prepared and stored in both polyvinyl chloride bags and glass bottles using 0.9% sodium chloride injection as a diluent. The study was performed using a validated and stability-indicating high-performance liquid chromatography method. The physical compatibility was assessed by a spectrometer. Furthermore, the pH measurement of each sample was measured electronically. All test solutions stored at 4°C or 25°C had a no >2% loss of the initial concentration throughout the 72-hour study period. All solutions remained clear and colorless throughout the study and were without precipitation or turbidity in any of the batches. The drug mixtures of MSS (0.4-0.8 mg/mL) and GH (0.03 mg/mL) in 0.9% sodium chloride injections were physically and chemically stable for at least 72 hours when stored at 4°C or 25°C in polyvinyl chloride bags or glass bottles.

Triflavones from Selaginella Doederllein Inhibited Hypoxia-induced, Pulmonary Vascular Remodeling Through PI3K/Akt.

CONTEXT: Pulmonary hypertension (PH) is a complication of numerous pulmonary conditions. Previous studies have confirmed that Selaginella doederleini has pharmacological effects against many cancers, and triflavones have been newly isolated as one of its active ingredients, with antioxidant and antitumor activities. The chronic hypoxia model is one of the models most used to study PH pathogenesis and treatment. OBJECTIVE: The present study was designed to investigate the protective effects of triflavones from selaginella doederlleini against PH and on the proliferation and apoptosis of ASMCs in a hypoxia-induced PH model in rats. METHODS: The research team performed an animal study. SETTING: The study took place at the Tongji Medical College at the Huazhong University of Science and Technology in Wuhan, Hubei, PR China. ANIMALS: The animals were 40 specific pathogen free (SPF), male SD rats weighing 200 ± 20 g each. INTERVENTION: The animals were divided into 4 groups, with 10 animals in each group: (1) the control group, (3) the hypoxia group (PH group), (3) the control + triflavones group (Tri group) and (4) the hypoxia + triflavones group (PH + Tri group). The rats in 2 hypoxia groups were exposed to 10% oxygen to induce PH, and the animals in the 2 control groups were exposed to room air, both for 3 consecutive weeks. Animals in the 2 triflavones groups were injected with 200 µL of triflavones-100 mg/mL dissolved in 0.9% normal saline-and the animals in the control and PH groups were injected with 200 µL of 0.9% normal saline. OUTCOME MEASURES: In vitro, the primary aorta smooth muscle cells (ASMCs) were isolated, and the proliferation and apoptosis of the ASMCs were assayed by CCK-8 kit and flow cytometry. The expression levels of the alpha-smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-ß1), and phosphoinositide 3-kinases (P13K)/ protein kinase B (Akt) in the ASMCs were also assayed by Western blot. RESULTS: Triflavones effectively decreased mPAP, the ratio of RV/ (LV + S), and the thickness of the arteries of the PH + Tri group. Furthermore, triflavones reversed the increased proliferation and inhibited apoptosis induced by chronic hypoxia for that group. Hypoxia increased TGF-ß1 protein expression and the activation of P13K/Akt, as shown in the PH group, and was abrogated by the triflavones. CONCLUSION: Triflavones are promising protective agents against PH due to their inhibitory effects on vascular remodeling through P13K/Akt signaling.

Ultrasonic Characteristics of Cardiovascular Changes in Children with Hutchinson-Gilford Progeria Syndrome: A Comparative Study with Normal Children and Aging People.

BACKGROUND: The cardiovascular characteristics of children with Hutchinson-Gilford progeria syndrome (HGPS) remain unclear. The present study is aimed at evaluating the cardiovascular changes with ultrasound examination in children with HGPS and compared these with those in normal children and older people. METHODS: Seven HGPS children, 21 age-matched healthy children, and 14 older healthy volunteers were evaluated by three-dimensional echocardiography (including strain analysis) and carotid elasticity examination with the echo-tracking technique. RESULTS: Children with HGPS had higher left ventricular ejection fraction (LVEF) and global longitudinal strain, when compared to older healthy volunteers (P < 0.05). However, these parameters were not significantly different, when compared to those in healthy children. Furthermore, children with HGPS had lower average peak times in the left ventricle, when compared with the other two groups. For the structure of the carotid artery detected by ultrasound, the abnormality rates were similar between children with HGPS and older healthy volunteers (83.3% vs. 71.4%). The elastic parameters, elastic modulus, stiffness parameter, and pulsed wave transmittal velocity of children with HGPS were lower, when compared to those in older healthy volunteers (P < 0.05), while they were higher with arterial compliance (P > 0.05). Furthermore, no significant difference existed among the vascular elastic parameters between HGPS and normal children. CONCLUSION: HGPS children had impaired left ventricular (LV) synchrony, when compared to normal children, although the difference in LVEF was not statistically significant. Furthermore, the structural abnormality of the carotid artery in HGPS children was similar to that in older people, although the index of elasticity appears to be more favorable. These results suggest that the cardiovascular system in HGPS children differs from natural aging.

Erratum: A germline alteration of ERBB2 increases the risk of breast cancer in Chinese Han women with a familial history of malignant tumors.

[This corrects the article DOI: 10.3892/ol.2019.10646.].

Swertiamarin protects neuronal cells from oxygen glucose deprivation/reoxygenation via TLR4/PARP1/NF-κB pathway.

Swertiamarin (STM) is a natural compound from Swertia mussotii Franch. (Gentianaceae) that exhibits various pharmacological effects. The current study tested the potential neuroprotective activity of STM in human neuroblastoma SH-SY5Y cells challenged with oxygen-glucose deprivation/reoxygenation (OGDR). Cell Counting Kit-8 assays were used to assess cell viability and the JC-1 assay were performed to evaluate changes in mitochondrial membrane potential (ΔΨm). The intracellular levels of ROS production were measured by 20,70-dichlorofuorescein diacetate (DCFH-DA) staining and flow cytometry. In addition, neuronal apoptosis was evaluated by staining with annexin V and flow cytometry. The determinations had also been made on TLR4-related proteins by Western blot analysis. Results show that exposure to OGDR significantly decreased cell viability but this decrease was attenuated by pretreatment with STM. STM also significantly attenuated declines in ΔΨm, inhibited OGDR-induced increases in intracellular ROS production, and reduced cell apoptosis. OGDR notably induced TLR4, Myd88, NF-κB p65 and PARP1 expression levels in the cells. However, treatment with STM reduced the expression of TLR4, Myd88, NF-κB p65 and PARP1. In conclusion, STM protected SH-SY5Y cells against OGDR-induced injury by attenuating increases in ROS levels and suppressing apoptosis, at least in part, via TLR4/PARP1/NF-κB pathway.

A germline alteration of ERBB2 increases the risk of breast cancer in Chinese Han women with a familial history of malignant tumors.

Previous studies have demonstrated that a family history of breast cancer is considered a risk factor, and hereditary factors may be involved in breast cancer pathogenesis. Next-generation sequencing techniques were used to analyze 111 cancer-associated genes in patients with breast cancer with a familial history of malignant tumors in the pre-experiment and a novel variant, receptor tyrosine-protein kinase erbB-2 (ERBB2) c.338G>A: p.R113Q was identified in two cases of breast cancer. ERBB2 is considered an important oncogene, and overexpression or mutation of the ERBB2 gene may lead to the occurrence or metastasis of tumors. To assess a potential association between rs185670819 and breast cancer, 117 patients with breast cancer and a familial history of any cancer, who were diagnosed by experienced pathologists at the Xijing Hospital (Shaanxi, China) between July 2015 and December 2016, were recruited. The presence of the missense variant was confirmed using bi-directional Sanger sequencing of samples from the patients with breast cancer and 250 healthy controls. The effects of the missense mutation on the structure and function of ERBB2 were analyzed in silico. The missense variant, R113Q, in patients with breast cancer with a familial history of malignant tumors in China, was present in 8 patients [6.8% (95% CI: 3.21-13.45)] and 3 of 250 healthy controls [1.2% (95% CI: 0.31-3.76; OR=6.04, 95% CI: 1.573-23.214, P=0.009)]. Of the 8 patients with the R113Q variant, 6 patients had a family history of cancer of the digestive system. The present study suggests that ERBB2 c.338G>A: p.R113Q may be a potential risk factor in the development and progression of breast cancer.

Performance and Reading Time of Automated Breast US with or without Computer-aided Detection.

BackgroundComputer-aided detection (CAD) systems may be used to help radiologists interpret automated breast (AB) US images. However, the optimal use of CAD with AB US has, to the knowledge of the authors, not been determined.PurposeTo compare the performance and reading time of different readers by using AB US CAD system to detect breast cancer in different reading modes.Materials and MethodsIn this retrospective study, 1485 AB US images (282 with malignant lesions, 695 with benign lesions, and 508 healthy) in 1452 women (mean age, 43.7 years; age range, 19-82 years) including 529 (36.4%) women who were asymptomatic were collected between 2016 and 2017. A CAD system was used to interpret the images. Three novice readers with 1-3 years of US experience and three experienced readers with 5-10 years of US experience were assigned to read AB US images without CAD, at a second reading (after the reader completed a full unaided interpretation), and at concurrent reading (use of CAD at the start of the assessment). Diagnostic performances and reading times were compared by using analysis of variance.ResultsFor all readers, the mean area under the receiver operating characteristic curve improved from 0.88 (95% confidence interval [CI]: 0.85, 0.91) at without-CAD mode to 0.91 (95% CI: 0.89, 0.92; P < .001) at the second-reading mode and 0.90 (95% CI: 0.89, 0.92; P = .002) at the concurrent-reading mode. The mean sensitivity of novice readers in women who were asymptomatic improved from 67% (95% CI: 63%, 74%) at without-CAD mode to 88% (95% CI: 84%, 89%) at both the second-reading mode and the concurrent-reading mode (P = .003). Compared with the without-CAD and second-reading modes, the mean reading time per volume of concurrent reading was 16 seconds (95% CI: 11, 22; P < .001) and 27 seconds (95% CI: 21, 32; P < .001) shorter, respectively.ConclusionComputer-aided detection (CAD) was helpful for novice readers to improve cancer detection at automated breast US in women who were asymptomatic. CAD was more efficient when used concurrently for all readers.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Slanetz in this issue.

Swertiamarin ameliorates carbon tetrachloride-induced hepatic apoptosis via blocking the PI3K/Akt pathway in rats.

Swertiamarin (STM) is an iridoid compound that is present in the Gentianaceae swertia genus. Here we investigated antiapoptotic effects of STM on carbon tetrachloride (CCl4)-induced liver injury and its possible mechanisms. Adult male Sprague Dawley rats were randomly divided into a control group, an STM 200 mg/kg group, a CCl4 group, a CCl4+STM 100 mg/kg group, and a CCl4+STM 200 mg/kg group. Rats in experimental groups were subcutaneously injected with 40% CCl4 twice weekly for 8 weeks. STM (100 and 200 mg/kg per day) was orally given to experimental rats by gavage for 8 consecutive weeks. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins were evaluated by western blot analysis. The expression of TGF-ß1, collagen I, collagen III, CTGF and fibronectin mRNA were estimated by qRT-PCR. The results showed that STM significantly reduced the number of TUNEL-positive cells compared with the CCl4 group. The levels of Bax and cleaved caspase-3 proteins, and TGF-ß1, collagen I, collagen III, CTGF, and fibronectin mRNA were significantly reduced by STM compared with the CCl4 group. In addition, STM markedly abrogated the repression of Bcl-2 by CCl4. STM also attenuated the activation of the PI3K/Akt pathway in the liver. These results suggested that STM ameliorated CCl4-induced hepatocyte apoptosis in rats.

Calculus Bovis Sativus up-regulates hepatic protein 2 (Mrp2) and Mrp4 in 17α-ethynylestradiol-induced cholestasis via a regulatory effect on ER signaling.

OBJECTIVE: To investigate the pathway through which Calculus Bovis Sativus (CBS) up-regulates hepatic multidrug resistance-associated protein 2 (Mrp2) and Mrp4 in 17α-ethynylestradiol (EE)-induced cholestasis. METHODS: Five groups of rats were designed: control group, EE+ICI182780 group, EE group, EE+CBS 50 mg/kg group and EE + CBS 150 mg/kg group. CBS (50 and 150 mg·kg－1·d－1 ) was orally given to rats by gavage for five consecutive days in coadministration with EE. The levels of cholestasis biomarkers, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL) were determined by biochemical methods. The bile flow was measured. The histopathology of the liver tissue was evaluated. The expression of Mrp2, Mrp3, Mrp4, estrogen receptor α (ERα) and ERß was determined by Western blotting. RESULTS: CBS markedly improved EE-induced cholestasis. EE exposure significantly reduced hepatic Mrp2 and Mrp4 expression compared with the control group. EE also dramatically up-regulated the expression of Mrp3. Compared to the EE group, CBS notably up-regulated hepatic Mrp2 and Mrp4 but failed to influence the Mrp3 level significantly. ICI182780, an ER antagonist, showed similar beneficial effects as CBS. Decreased expression of Mrp2 and Mrp4 caused by EE was also restored by ICI182780. Additionally, EE significantly induced he- patic ERα expression, which was reversed by ICI182780 or CBS (150 mg/kg) treatment, suggesting that CBS exerted a moderate regulatory effect on ER signaling. CONCLUSION: CBS up-regulated hepatic Mrp2 and Mrp4 expression in EE-induced cholestasis, which might be associated with its regulation of ER signaling.

Cardiotoxicity of Consolida rugulosa, a poisonous weed in Western China.

Poisonous weeds are a global problem since they not only hinder local economic development, but also cause ecological harm. Consolida rugulosa (family Ranunculaceae) is a weed that is widespread in Northwestern China and causes severe poisoning when ingested by livestock. In the present study, we purified the toxins in this plant and investigated their mechanism of action. Five natural diterpene alkaloids (compounds 1-5)-including two new compounds (1 and 2)-were isolated, and five semi-synthetic derivatives (6-10) were synthesised based on 4 or 5 for structure-activity analysis. The toxicity of the compounds was evaluated in vitro with lactate dehydrogenase (LDH) assay. All of the compounds-especially 1-stimulated LDH release in primary cultured rat myocardial cells, an effect that was blocked by the Na+ channel blocker lidocaine. Electrocardiography revealed that rats treated with 1 had severe arrhythmia, while heart Doppler echocardiography and analysis of serum biomarkers levels revealed that administration of 1 for 15 days induced changes in cardiac structure and myocardial enzyme levels. These effects were antagonised by lidocaine treatment. Thus, diterpene alkaloids are the main compounds responsible for the cardiotoxicity of C. rugulosa, which can be mitigated by co-administration of lidocaine.

Antibiotic anisomycin selectively targets leukemia cell lines and patient samples through suppressing Wnt/ß-catenin signaling.

Chronic myeloid leukemia (CML) responds well to BCR-ABL tyrosine kinase inhibitors (TKI), such as imatinib and dasatinib. However, these inhibitors have been less effective as single agents in the blast phase-CML. In this work, we show that anisomycin, a clinically available drug, targets CML cells at all stages of development and enhances BCR-ABL TKIs' efficacy. Anisomycin at nanomolar concentration inhibits proliferation and induces apoptosis in a panel of CML cell lines in a dose-dependent manner. It induces apoptosis CD34 stem/progenitor cells isolated from patients with blast phase CML. Using colony formation and serial replating assays, we further show that anisomycin inhibits CML CD34 cell differentiation, proliferation and self-renewal. Additionally, anisomycin is less effective in normal bone marrow (NBM) CD34 cells, suggesting the selective anti-leukemia activity of anisomycin. Combination of anisomycin with imatinib or dasatinib achieves significantly better efficacy than TKI alone in leukemia cell lines and patient samples while sparing normal counterparts. Mechanistically, we demonstrate that p38 MAPK/JNK activation is not required for anti-leukemia activities of anisomycin. Instead, anisomycin displays preferential inhibitory effects to Wnt/ß-catenin-mediated signaling in CML. Our work provides the preclinical evidence on the potent efficacy of anisomycin in leukemia and its mechanisms of action. Our work suggests that anisomycin is a potential drug to overcome resistance to BCR-ABL TKI treatment in blast phase CML.

Swertiamarin attenuates carbon tetrachloride (CCl4)-induced liver injury and inflammation in rats by regulating the TLR4 signaling pathway

The aim of the present study is to illustrate the effects of swertiamarin (STM), a natural iridoid from herbal medicines, on hepatic inflammation induced by carbon tetrachloride (CCl4) in rats. Male Sprague Dawley rats were exposed to CCl4 with or without STM co-administration for 8 weeks. Our results revealed that STM administration (100 and 200 mg/kg b.w.) significantly attenuated inflammation in livers of CCl4-treated rats. STM remarkably reduced the production of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-1a (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) in liver tissue of CCl4-treated rats. In addition, STM treatment downregulated connective tissue growth factor (CTGF) and ser307pIRS-1 expression, which was induced by CCl4 exposure. In the process of exploring the anti-inflammatory mechanisms of STM action, we demonstrated that STM significantly inhibited Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 expression in the liver. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by STM was, at least in part, due to its regulation of the TLR4 /NF-κB signaling pathway

Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-ß1/Smad Pathways.

BACKGROUND/AIMS: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. METHOD: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. RESULTS: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-ß1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. CONCLUSION: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-ß1/Smad pathways.

Antiplatelet drug ticagrelor delays gastric ulcer healing in rats.

Adenosine diphosphate P2Y12 receptor antagonist clopidogrel is not sufficiently safe for the gastric mucosa in patients with high risk of peptic ulcer, since it may impair healing of gastric erosions. However, the safety of the novel P2Y12 receptor antagonist ticagrelor in the gastric mucosa has not been elucidated to date. The present study aimed to examine whether ticagrelor delays gastric ulcer healing and to elucidate the involved mechanisms. Gastric kissing ulcers were produced in rats by luminal application of acetic acid solution, and ticagrelor was administered at dose of 10 or 20 mg/kg/day orally for 7 days. On day 8 after ulcer induction, the ulcer size, mucosal epithelial cell proliferation of the ulcer margin, expression levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and signal transduction pathways for cell proliferation and angiogenesis were measured and compared between the ticagrelor-treated and untreated model groups. The results revealed that the ulcer size was significantly greater in the ticagrelor-treated group compared with the model group, while the mucosal epithelial cell proliferation of the ulcer margin was significantly decreased in the ticagrelor-treated group. In addition, ticagrelor significantly decreased the ulcer-stimulated expression levels of EGF, VEGF, phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated P38 mitogen-activated protein kinase and nuclear factor-κB P65 at the ulcer margin (P<0.05). These findings suggested that ticagrelor delayed gastric ulcer healing. Furthermore, the possible mechanisms underlying the effect of ticagrelor were associated with its functions of attenuating the expression levels of VEGF and EGF, as well as suppressing the phosphorylation activation of ERK1/2, P38 and nuclear factor-κB P65. Finally, the gastric epithelial cell proliferation and angiogenesis were also inhibited.

[Progress in genetic research on psoriatic arthritis].

Psoriatic arthritis is a form of inflammatory arthritis found among patients with psoriasis, which can lead to pain, swelling or stiffness in one or more joints and even movement disorders. Epidemiological studies have shown a higher heritability for psoriatic arthritis compared with psoriasis vulgaris. With the evolvement of DNA sequencing, many genes have been associated with psoriasis vulgaris and psoriatic arthritis, which included MHC, TNF, LCE, IL23R, IL12B, TRAF3IP2 and TNFAIP3, though some, such as MHC, IL-13 and PTPN22, have been specifically associated with psoriatic arthritis. These studies have laid a foundation for risk prediction, diagnosis and drug development for psoriatic arthritis.