Clinical value of ultrasonic indicators in predicting the outcome of caesarean scar pregnancy after pregnancy termination.

BACKGROUND: To investigate the predictive value of ultrasound indicators in early pregnancy for the outcome of caesarean scar pregnancy (CSP) after pregnancy termination. METHODS: This study retrospectively analysed the ultrasound images of 98 CSP patients who underwent transabdominal ultrasound-guided hysteroscopic curettage during early pregnancy at Changsha Hospital for Maternal and Child Health Care between January 2017 and October 2021. Patients were equally divided into a case group and a control group. The case group included 49 CSP patients with postoperative complications, such as intraoperative blood loss ≥ 200 ml or retained products of conception (RPOC). The remaining 49 CSP patients, with similar age and gestational age and with good postoperative outcomes, such as intraoperative blood loss ≤ 50 ml and no RPOC, were included in the control group. CSP was classified into three types according to the location of the gestational sac (GS) relative to the uterine cavity line (UCL) and serosal contour. Differences in ultrasound indicators between the case and control group were compared. RESULTS: There were significant differences between the case and control groups in the mean gestational sac diameter (MGSD), residual myometrium thickness (RMT) between the GS and the bladder, blood flow around the GS at the site of the previous caesarean incision, and types of CSP (P < 0.05). The rs of each ultrasound indicator were as follows: 0.258, -0.485, 0.369, 0.350. The optimal threshold for predicting good postoperative outcomes, such as intraoperative blood loss ≤ 50 ml and no RPOC, by receiver operating characteristic (ROC) curve analysis of the RMT was 2.3 mm. CONCLUSION: Our findings show that the RMT, blood flow around the GS at the site of the previous caesarean incision, and types of CSP have a low correlation with postoperative complications, such as intraoperative blood loss ≥ 200 ml or RPOC, of early pregnancy termination in patients with CSP. To some extent, this study may be helpful for clinical prognostic prediction of patients with CSP and formulation of treatment strategies. Given the low correlation between these three indicators and postoperative complications, further studies are needed to identify indicators that can better reflect the postoperative outcomes of CSP patients.

Radiomics-based ultrasound models for thyroid nodule differentiation in Hashimoto's thyroiditis.

Background: Previous models for differentiating benign and malignant thyroid nodules(TN) have predominantly focused on the characteristics of the nodules themselves, without considering the specific features of the thyroid gland(TG) in patients with Hashimoto's thyroiditis(HT). In this study, we analyzed the clinical and ultrasound radiomics(USR) features of TN in patients with HT and constructed a model for differentiating benign and malignant nodules specifically in this population. Methods: We retrospectively collected clinical and ultrasound data from 227 patients with TN and concomitant HT(161 for training, 66 for testing). Two experienced sonographers delineated the TG and TN regions, and USR features were extracted using Python. Lasso regression and logistic analysis were employed to select relevant USR features and clinical data to construct the model for differentiating benign and malignant TN. The performance of the model was evaluated using area under the curve(AUC), calibration curves, and decision curve analysis(DCA). Results: A total of 1,162 USR features were extracted from TN and the TG in the 227 patients with HT. Lasso regression identified 14 features, which were used to construct the TN score, TG score, and TN+TG score. Univariate analysis identified six clinical predictors: TI-RADS, echoic type, aspect ratio, boundary, calcification, and thyroid function. Multivariable analysis revealed that incorporating USR scores improved the performance of the model for differentiating benign and malignant TN in patients with HT. Specifically, the TN+TG score resulted in the highest increase in AUC(from 0.83 to 0.94) in the clinical prediction model. Calibration curves and DCA demonstrated higher accuracy and net benefit for the TN+TG+clinical model. Conclusion: USR features of both the TG and TN can be utilized for differentiating benign and malignant TN in patients with HT. These findings highlight the importance of considering the entire TG in the evaluation of TN in HT patients, providing valuable insights for clinical decision-making in this population.

Improving endothelial cell junction integrity by diphenylmethanone derivatives at oxidative stress: A dual-action directly targeting caveolar caveolin-1.

Directly targeting caveolar caveolin-1 is a potential mechanism to regulate endothelial permeability, especially during oxidative stress, but little evidence on the topic limits therapeutics discoveries. In this study, we investigated the pharmacological effect of an antioxidant LM49 (5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanoe) and its five diphenylmethanone derivatives on endothelial permeability and establish two distinct mechanisms of action. Multiplex molecular assays with theoretical modeling indicate that diphenylmethanone molecules, including LM49, directly bind the caveolin-1 steric pocket of ASN53/ARG54, ILE49/ASP50, ILE18, LEU59, ASN60, GLU48 and ARG19 residues. They also indicated dynamic binding-affinity for diphenylmethanone derivatives. First, this molecular interaction at caveolin-1 pocket inhibits its phosphorylation at TYR14 residue in H2O2-injured endothelial cell. A positive correlation was established between diphenylmethanone derivative binding-affinity and caveolin-1 phosphorylation inhibition. Inhibition of caveolin-1 phosphorylation, however, was independent of the LM49-mediated variation of protein tyrosine kinase activity, suggesting a direct blockage of adenosine triphosphate substrate diffusion into cavelion-1 structure. Second, LM49 increases the expression of cellular adhesive and tight junction proteins, VE-cadherin and occludin, in H2O2-injured cell, in a dose dependent manner. A leakage assay of fluorescein isothiocyanate-labeled dextran 40 across cell monolayer suggested improvement in endothelial barrier integrity with diphenylmethanone treatments. Our results demonstrate a direct targeting effect of caveolin-1 on endothelial permeability, and should guide the diphenylmethanone therapy against oxidative stress-induced junction dysfunction, especially at caveolar membrane invagination.

A novel effector, CsSp1, from Bipolaris sorokiniana, is essential for colonization in wheat and is also involved in triggering host immunity.

The hemibiotrophic pathogen Bipolaris sorokiniana causes root rot, leaf blotching, and black embryos in wheat and barley worldwide, resulting in significant yield and quality reductions. However, the mechanism underlying the host-pathogen interactions between B. sorokiniana and wheat or barley remains unknown. The B. sorokiniana genome encodes a large number of uncharacterized putative effector proteins. In this study, we identified a putative secreted protein, CsSp1, with a classic N-terminal signal peptide, that is induced during early infection. A split-marker approach was used to knock out CsSP1 in the Lankao 9-3 strain. Compared with the wild type, the deletion mutant ∆Cssp1 displayed less radial growth on potato dextrose agar plates and produced fewer spores, and complementary transformation completely restored the phenotype of the deletion mutant to that of the wild type. The pathogenicity of the deletion mutant in wheat was attenuated even though appressoria still penetrated the host. Additionally, the infectious hyphae in the deletion mutant became swollen and exhibited reduced growth in plant cells. The signal peptide of CsSp1 was functionally verified through a yeast YTK12 secretion system. Transient expression of CsSp1 in Nicotiana benthamiana inhibited lesion formation caused by Phytophthora capsici. Moreover, CsSp1 localized in the nucleus and cytoplasm of plant cells. In B. sorokiniana-infected wheat leaves, the salicylic acid-regulated genes TaPAL, TaPR1, and TaPR2 were down-regulated in the ∆Cssp1 strain compared with the wild-type strain under the same conditions. Therefore, CsSp1 is a virulence effector and is involved in triggering host immunity.

Reliability and validity of SHMS v1.0 for suboptimal health status assessment of Tianjin residents and factors affecting sub-health: A cross-sectional study.

ABSTRACT: The study aimed to explore the reliability and validity of the Sub-Health Measurement Scale version 1.0 (SHMS v1.0) for the assessment of the suboptimal health status (SHS) of Tianjin residents.This was a cross-sectional study that surveyed 2640 urban residents in Tianjin from June 2016 to January 2018. Demographic and clinical characteristics were collected. Each subject completed the SHMS v1.0 and Short Form-36 (SF-36) scale assessments.The retest coefficient was 0.675. The overall Cronbach's α coefficient was 0.921. The correlation between SHMS v1.0 and SF-36 was 0.781 (P < .01). The SHS frequency increased with age, from 62.4% in participants ≤25 years of age to 72.8% in those ≥ 56 years of age. The multivariable analysis showed that female sex (P < .001), age >25 years old (P = .009), bachelor degree or above (P < .001), obesity (P < .0), regular smoking (P = .043), frequent drinking (P = .045), sleep time < 6 hours (P = .006), working time >10 hours (P < .001), physical exercise <5 times/mo (P < .001), and adverse events >9 (P < .001) were associated with SHS.The prevalence of SHS is high among urban residents in Tianjin.

MicroRNA-29b-3p enhances radiosensitivity through modulating WISP1-mediated mitochondrial apoptosis in prostate cancer cells.

Radiotherapy is frequently applied for clinically localized prostate cancer while its efficacy could be significantly hindered by radioresistance. MicroRNAs (miRNAs) are important regulators in mediating cellular responses to ionizing radiation (IR), and strongly associate with radiosensitivity in many cancers. In this study, enhancement of radiosensitivity by miR-29b-3p was demonstrated in prostate cancer cell line LNCaP in vitro. Results showed that miR-29b-3p expression was significantly upregulated in response to IR from both X-rays and carbon ion irradiations. Knockdown of miR-29b-3p resulted in radioresistance while overexpression of miR-29b-3p led to increased radiosensitivity (showing reduced cell viability, suppressed cell proliferation and decreased colony formation). In addition, miR-29b-3p was found to directly target Wnt1-inducible-signaling protein 1 (WISP1). Inhibition of WISP1 facilitated the mitochondrial apoptosis pathway through suppressing Bcl-XL expression while activating caspase-3 and poly (ADP-ribose) polymerase (PARP). The results indicated that miR-29b-3p was a radiosensitizing miRNAs and could enhance radiosensitivity of LNCaP cells by targeting WISP1. These findings suggested a novel treatment to overcome radioresistance in prostate cancer patients, especially those with higher levels of the WISP1 expression.

Fetal double aortic arch: prenatal sonographic and postnatal computed tomography angiography features, associated abnormalities and clinical outcomes.

BACKGROUND: Fetal double aortic arch (DAA) malformation is a rare congenital heart disease with few reported cases in the literature. We aimed to investigate the characteristics of prenatal ultrasound and postnatal computed tomography angiography (CTA) of DAA and to describe the associated anomalies and clinical outcomes to improve prenatal diagnosis and assist in perinatal management. METHODS: The obstetric ultrasound imaging databases of seven tertiary referral centers were reviewed retrospectively to identify fetuses with a prenatal diagnosis of DAA between January 2013 and December 2018. Ultrasonographic findings, associated anomalies, genetic abnormalities, postnatal CTA images, and long-term postnatal outcomes were evaluated. RESULTS: A total of 36 cases out of 40 prenatally diagnosed DAA fetuses were confirmed by postnatal diagnosis (fetal autopsy, CTA, and surgery). In this cohort of 36 confirmed cases, 24 (67%) were isolated anomalies, while 12 (33%) were associated with intracardiac or extracardiac anomalies, and 2 (6%) had a 22q11.2 chromosome deletion. Among nine cases of pregnancy termination with a fetal autopsy, 7 had other abnormalities. Among the remaining 27 live births, 16 (59%) were asymptomatic and 11 (41%) received surgical treatment due to tracheal or esophageal compression symptoms, all with satisfactory outcomes. Prenatal echocardiography showed that DAA was mainly characterized by a bifurcation of the ascending aorta into the right and left aortic arch and the formation of a complete O-shaped vascular ring around the trachea on the three-vessel tracheal view. A variant in the aortic arch branching pattern was found for the first time. The airway obstruction, branching pattern, and atretic arch of DAA were clearly shown by postnatal CTA. CONCLUSIONS: Fetal DAA has unique features on prenatal echocardiography and postnatal CTA, and systematic prenatal examination and timely postnatal CTA evaluation are required. A certain proportion of intracardiac and extracardiac abnormalities are associated with DAA, but the probability of chromosome abnormalities is low, especially for isolated DAA.The clinical outcomes of isolated DAA are favorable, even if surgery is performed due to symptoms. Determining whether other malformations or chromosomal anomalies exist is crucial for prognosis evaluation and prenatal counseling.

The antitumor effect of hinesol, extract from Atractylodes lancea (Thunb.) DC. by proliferation, inhibition, and apoptosis induction via MEK/ERK and NF-κB pathway in non-small cell lung cancer cell lines A549 and NCI-H1299.

Lung cancer (especially, non-small cell lung cancer [NSCLC]) is one of the most malignant cancers in the world. Hinesol is the major component of the essential oil of Atractylodes lancea (Thunb.) DC and possesses the most promising anticancer function. However, the effects and molecular mechanism of hinesol on antiproliferation in NSCLC cells has not been well understood. In this study, we found that hinesol effectively inhibited the A549 and NCI-H1299 cells in a dose- and time-dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. In addition, hinesol induced cell cycle arrest at G0/G1 phase and apoptosis assessed by flow cytometry in A549 cells. Furthermore, Western blot analysis showed that hinesol decreased phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, IκBα, and p65 inhibited the expressions of Bcl-2, cyclin D1 and upregulated the expression of Bax. Based on these results, hinesol might be a potential drug candidate of anti-NSCLC for therapy.

Prenatal diagnosis of fetal intraabdominal extralobar pulmonary sequestration: a 12-year 3-center experience in China.

To provide useful information for diagnosing and predicting fetal intraabdominal extralobar pulmonary sequestration (IEPS), a retrospective review of diagnostic approaches was conducted. Ultrasonography was performed serially in 21 fetuses with IEPS from 2005 to 2017. Prenatal sonographic features, treatment, and outcomes of each case were evaluated and collected. These cases of IEPS were also compared to 43 cases previously reported by other researchers from 1986 to 2017. Of the 21 sonographic features, 14 (67%) were hyperechoic, 21 (100%) were well circumscribed, and 17 (81%) depicted a mass that shifted with fetal breaths/hiccups non-synchronized with adjacent organs (sliding sign). Feeding arteries were detected prenatally in 18 patients (86%). The lesion volume was 10.17 ± 4.66 cm3, the congenital cystic adenomatoid malformation volume ratio and cardiothoracic ratio were in normal range. The gestational age at diagnosis, location and echotexture of the lesion, and rate of surgical treatment were similar to previous studies, but with a significantly higher rate of detected feeding arteries (P < 0.01), and associated anomalies (P < 0.01). All infants who underwent surgery after birth had satisfactory outcomes. The sliding sign and feeding artery are essential features of IEPS in prenatal diagnosis.

5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone attenuates LPS-induced inflammation and ROS production in EA.hy926 cells via HMBOX1 induction.

Inflammation and reactive oxygen species (ROS) are important factors in the pathogenesis of atherosclerosis (AS). 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone (TDD), possess anti-atherogenic properties; however, its underlying mechanism of action remains unclear. Therefore, we sought to understand the therapeutic molecular mechanism of TDD in inflammatory response and oxidative stress in EA.hy926 cells. Microarray analysis revealed that the expression of homeobox containing 1 (HMBOX1) was dramatically upregulated in TDD-treated EA.hy926 cells. According to the gene ontology (GO) analysis of microarray data, TDD significantly influenced the response to lipopolysaccharide (LPS); it suppressed the LPS-induced adhesion of monocytes to EA.hy926 cells. Simultaneously, TDD dose-dependently inhibited the production or expression of IL-6, IL-1ß, MCP-1, TNF-α, VCAM-1, ICAM-1 and E-selectin as well as ROS in LPS-stimulated EA.hy926 cells. HMBOX1 knockdown using RNA interference attenuated the anti-inflammatory and anti-oxidative effects of TDD. Furthermore, TDD inhibited LPS-induced NF-κB and MAPK activation in EA.hy926 cells, but this effect was abolished by HMBOX1 knockdown. Overall, these results demonstrate that TDD activates HMBOX1, which is an inducible protective mechanism that inhibits LPS-induced inflammation and ROS production in EA.hy926 cells by the subsequent inhibition of redox-sensitive NF-κB and MAPK activation. Our study suggested that TDD may be a potential novel agent for treating endothelial cells dysfunction in AS.

Bidirectional effects of moxifloxacin on the pro­inflammatory response in lipopolysaccharide­stimulated mouse peritoneal macrophages.

Sepsis is a systemic inflammatory condition in response to life­threatening infections, and macrophages are a key source of inflammatory cytokines. Moxifloxacin (MXF) has antibacterial activity in Gram­positive and Gram­negative bacteria. The present study investigated the effects of MXF on a lipopolysaccharide (LPS)­stimulated inflammatory response and gene expression in macrophages. Peritoneal macrophages were isolated from male C57BL/6J mice and treated with LPS and/or MXF. The mRNA and protein expression of toll­like receptor 4 (TLR4), sphingosine kinase 1 (SPHK1) and nuclear factor (NF)­κB was determined by quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The expression of tumor necrosis factor (TNF)­α and interleukin (IL)­6 was determined with ELISAs. The data demonstrated that MXF dose­dependently decreased the viability of macrophages, and 8 and 16 µg/ml MXF prevented the LPS­induced increase in TLR4, SPHK1, NF­κB p65, TNF­α and IL­6 expression. The inhibition was most effective at a concentration of 16 µg/ml MXF, whereas, 64 µg/ml MXF exerted a pro­inflammatory effect. Collectively, the data demonstrated a bidirectional effect of MXF: Lower MXF concentrations (8 and 16 µg/ml) inhibited the inflammatory response; however, a higher MXF concentration (64 µg/ml) had a pro­inflammatory effect on LPS­treated mouse peritoneal macrophages. In conclusion, these results suggested the importance of MXF as an inhibitor of the inflammatory response at an optimal dose. MXF inhibition of the inflammatory response may be mediated by TLR4 signaling.

[Gene Polymorphism of Inflammation-related Cytokines Correlates with the Susceptibility to DLBCL].

OBJECTIVE: To investigate the relationship of gene polymorphisms of inflammattion related cytokines with incidence of diffuse large B-cell lymphoma(DLBCL) in Gansu Han population. METHODS: The gene polymorphism of inflammation-related cytokines were detected by high-resolution melting(HRM) curve. RESULTS: The homozygous CC genotype carrying IL-1RA rs4251961 gene locus was related with the risk of DLBCL in comparison with homozygous TT, the OR was 0.83 of homozygous CC, 95% CI=0.697-0.997,P<0.05), while the C allele of IL-1RA rs4251961 gene locus significantly correlated with the high incidence of diffuse large B-cell lymphoma compared with T allele(OR=8.83, 95% CI=1.909-40.813,P<0.01). CONCLUSION: The minor allele C of IL-1RA rs4251961 gene locus significantly relates with the susceptibility to DLBCL.

Identification of the long non­coding RNA LET as a novel tumor suppressor in gastric cancer.

Long non-coding RNAs (lncRNAs) have emerged recently as important factors in regulating fundamental biological processes. Alterations in the expression and function of lncRNAs have been observed to promote tumor formation, progression and metastasis. Although downregulation of the expression levels of LET lncRNA in several tumors has been reported, its role in gastric cancer remains unknown. The aim of the present study was to investigate the expression and function of LET in gastric cancer development. The expression levels of LET in 37 pairs of gastric cancer and adjacent non­tumor tissues were detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). In addition, LET expression in gastric cancer cell lines was analyzed by RT­qPCR assay analysis. Furthermore, the impact of LET on cell proliferation, migration and apoptosis were detected using the cell counting kit­8, wound scratch and ELISA assays, respectively. The results demonstrated that the expression level of LET was downregulated in gastric cancer tissues and cell lines (SGC­7901 and MGC­803) compared with normal tissues and a normal human gastric epithelial cell line (GES­1). Restoration of LET expression using a synthesized recombinant overexpression vector transfected into SGC­7901 and MGC­803 cells, significantly inhibited cell proliferation and migration, and promoted cell apoptosis in vitro. The present study is the first to demonstrate that LET may function as a tumor suppressor in gastric cancer. The results indicate that LET may be a promising biomarker and/or a therapeutic target for gastric cancer.

Identification a novel tumor-suppressive hsa-miR-599 regulates cells proliferation, migration and invasion by targeting oncogenic MYC in hepatocellular carcinoma.

Increasing evidences have demonstrated that microRNAs (miRNAs) act an essential role in regulating tumor progression and metastasis. Previous miRNAs microarray data showed that hsa-miR-599 is lower expressed in hepatocellular carcinoma (HCC); however, the function and molecular mechanism of hsa-miR-599 on HCC has not been well illustrated. Here, we first analyzed the expression level of hsa-miR-599 in HCC tissues and cell lines by real-time reverse-transcription PCR (qRT-PCR). Interestingly, we found that hsa-miR-599 was significantly down-regulated in the examined HCC tissues and cell lines. Then cells proliferation, migration and invasion were assessed by MTT, wound-healing and trans-well assay respectively. The results showed that over-expression of hsa-miR-599 resulted in inhibited HCC cells proliferation, migration and invasion in vitro. In addition, dual-luciferase reporter assay, qRT-PCR and Western blot analyzes were used to confirm MYC (v-myc avian myelocytomatosis viral oncogene homolog) as a target gene of hsa-miR-599. MYC expression was up-regulated in HCC tissues and cell lines, and restoration of hsa-miR-599 could remarkably decreased the mRNA and protein levels of MYC. Moreover, over-expression of MYC partly reversed hsa-miR-599-mediated inhibition of HCC cells proliferation, migration and invasion in vitro. Taken together, our data demonstrate that hsa-miR-599 acts as a tumor suppressor and inhibits HCC cells proliferation, migration and invasion by partly targeting oncogenic MYC, which hints that hsa-miR-599 can be a diagnostic and therapeutic biomarker in HCC.

Oxidative stress and spermatogenesis suppression in the testis of cadmium-treated Bombyx mori larvae.

Bombyx mori L. (B. mori) were exposed to cadmium chloride (CdCl2) incorporated in an artificial diet (0, 6.25, 12.5, 25, and 50 mg kg(-1)) throughout the larval stage. Changes in malondialdehyde (MDA) and reduced glutathione (GSH) contents and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as their corresponding messenger RNA (mRNA) levels in the testes of the fifth instar larvae were evaluated. Additionally, spermatozoon deformation in the testes was examined. Upon Cd treatment, the MDA content in the testes was significantly increased in a concentration-dependent manner. Cd-exposed larvae had increased levels of glutathione. Pearson's correlation analysis revealed that SOD and CAT activities were positively correlated (R (2) = 0.605, P = 0.017). The changing trends in the mRNA levels of these enzymes were not always consistent with those of enzymatic activities. Alterations in GSH-Px activities and mRNA levels were positively correlated (R (2) = 0.771, P < 0.01). Morphological analysis revealed that Cd deformed and affected the maturation of spermatozoa. Our results collectively support a relationship between Cd and alterations in the levels of antioxidant enzymes in B. mori testes.

Knockdown of sphingosine kinase 1 inhibits the migration and invasion of human rheumatoid arthritis fibroblast-like synoviocytes by down-regulating the PI3K/AKT activation and MMP-2/9 production in vitro.

To investigate the potential regulation of sphingosine kinase 1 (SPHK1) on the migration, invasion, and matrix metalloproteinase (MMP) expression in human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). RA-FLS were transfected control siRNA or SPHK1 siRNA. The migration and invasion of unmanipulated control, control siRNA or SPHK1 siRNA- transfected RA-FLS in vitro were measured by the transwell system. The relative levels of SPHK1, PI3K, and AKT as well as AKT phosphorylation in RA-FLS were determined by Western blot. The levels of MMP-2/9 secreted by RA-FLS were detected by ELISA. Knockdown of SPHK1 significantly inhibited the spontaneous migration and invasion of RA-FLS, accompanied by significantly reduced levels of PI3K expression and AKT phosphorylation. Similarly, treatment with LY294002, an inhibitor of the PI3K/AKT pathway, inhibited the migration and invasion of RA-FLS. Knockdown of SPHK1 and treatment with the inhibitor synergistically inhibited the migration and invasion of RA-FLS, by further reducing the levels of PI3K expression and AKT phosphorylation. In addition, knockdown of SPHK1 or treatment with LY294002 inhibited the secretion of MMP-2 and MMP-9, and both synergistically reduced the production of MMP-2 and MMP-9 in RA-FLS in vitro. Knockdown of SPHK1 expression inhibits the PI3K/AKT activation, MMP-2 and MMP-9 expression, and human RA-FLS migration and invasion in vitro. Potentially, SPHK1 may be a novel therapeutic target for RA.

Comparison of the Inhibitory Potential of Bavachalcone and Corylin against UDP-Glucuronosyltransferases.

Bavachalcone and corylin are two major bioactive compounds isolated from Psoralea corylifolia L., which has been widely used as traditional Chinese medicine for many years. As two antibiotic or anticancer drugs, bavachalcone and corylin are used in combination with other drugs; thus it is necessary to evaluate potential pharmacokinetic herb-drug interactions (HDI) of the two bioactive compounds. The aim of the present study was to compare the effects of liver UDP-glucuronosyltransferase (UGT) 1A1, UGT1A3, UGT1A7, UGT1A8, UGT 1A10, and UGT2B4 inhibited by bavachalcone and corylin. 4-Methylumbelliferone (4-MU) was used as a nonspecific "probe" substrate. Bavachalcone had stronger inhibition on UGT1A1 and UGT1A7 than corylin which did not inhibit UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A10, and UGT2B4. Data fitting using Dixon and Lineweaver-Burk plots demonstrated the noncompetitive inhibition of bavachalcone against UGT1A1 and UGT1A7-mediated 4-MU glucuronidation reaction. The values of inhibition kinetic parameters (Ki) were 5.41 µ M and 4.51 µ M for UGT1A1 and UGT1A7, respectively. The results of present study suggested that there was a possibility of UGT1A1 and UGT1A7 inhibition-based herb-drug interaction associated with bavachalcone and provided the basis for further in vivo studies to investigate the HDI potential between bavachalcone and UGT substrates.

[Chronotoxicology of fenvalerate on the male rats reproductive system].

OBJECTIVE: To study the chronotoxicity and mechanism of fenvalerate (Fen) on the male reproductive system. METHODS: Forty-nine healthy clean SD rats in a 12h: 12h light-dark photoperiod, which were divided into seven groups: control group and six Fen groups (Fen 2, Fen 6, Fen 10, Fen 14, Fen 18, Fen 22). Fen groups were administered by intra-gastric injection of Fen (12 mg/kg BW) respectively at corresponding zeitgeber time (ZT 02, ZT 06, ZT 10, ZT 14, ZT 18, ZT 22) for 30 days. The control group rats were administered with equal volume of edible blend oil. One side testicular was used to make HE paraffin slice. Germ cell (Daily sperm production, DSP. Sperm live rate, SLR. Abnormal sperm rate, ASR), the activities testicular mark enzymes and the levels of Sex hormones (testosterone, T, estradiol, E2) in testicular were measured. RESULTS: Compared with the control group, Fen cause the pathological changes of testicular tissue in rats, and the most serious injuries occurred in ZT 18. DSP, SLR, ACP and T in testicular were decreased, ASR and E2 were increased. Results from Cosinor analysis showed that Circadian rhythms of the changes compared to the control group in DSP, SLR and ACP were validated, and sensitive point in time to Fen was respectively at ZT 04, ZT 14, ZT 23. CONCLUSION: The results suggested that the effects of Fen on male reproductive function were time-dependent in a circadian day.