Green synthesis and anti-tumor efficacy via inducing pyroptosis of novel 1H-benzo[e]indole-2(3H)-one spirocyclic derivatives.

Pyroptosis induction is anticipated to be a new approach to developing anti-tumor medications. A novel class of spirocyclic compounds was designed by hybridization of 1H-Benzo[e]indole-2(3H)-one with 1,4-dihydroquinoline and synthesized through a new green "one-pot" synthesis method using 10 wt% SDS/H2O as a solvent to screen novel tumor cell pyroptosis inducers. The anti-tumor activity of all compounds in vitro was determined by the MTT method, and a fraction of the compounds showed good cell growth inhibitory activity. The quantitative structure-activity relationship models of the compounds were established by artificial intelligence random forest algorithm (R2 = 0.9656 and 0.9747). The ideal compound A9 could, in a concentration-dependent manner, prevent ovarian cancer cells from forming colonies, migrating, and invading. Furthermore, A9 could significantly induce pyroptosis and upregulate the expression of pyroptosis-related proteins GSDME-N, in addition to inducing apoptosis and mediating the expression of apoptosis-related proteins in ovarian cancer cells. A9 (5 mg/kg) significantly reduced tumor volume and weight of ovarian cancer in vivo, decreased caspase-3 expression in tumor tissue, and induced the production of GSDME-N. This study provides a green and efficient atom-economic synthesis method for 1H-Benzo[e]indole-2(3H)-one spirocyclic derivatives and a promising pyroptosis inducer with anti-tumor activity.

Clinical value of quantitative analysis of contrast-enhanced ultrasonography in the differential diagnosis of benign and malignant pelvic tumors.

Background: Cervical cancer, endometrial cancer, and ovarian cancer are among the top 10 most common cancers in women, with ovarian cancer in particular being considered a "silent killer". Therefore, early detection, diagnosis, and treatment constitute important means of care for women's health. This study investigated the clinical value of the quantitative analysis of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign and malignant pelvic tumors. Methods: CEUS was performed on 151 patients with pelvic masses. Subsequently, a qualitative diagnosis was completed using the image enhancement features and tumor parameters. A multiparametric analysis of CEUS images was performed, which included the following parameters: arrival time (AT), time to peak (TTP), peak intensity (PI), and ascent slope (AS). In addition, the qualitative diagnostic efficiency of CEUS was assessed in a multiparametric analysis, and the results were compared with pathological findings. Results: The patients in the malignant group were older (P=0.001) and had larger lesion PI values (P<0.01) than those in the benign group. The PI difference (PId) and the AS difference (ASd) showed statistical differences (P<0.01) between the myometrium and lesion tissues in the same patient. Moreover, the PId and ASd showed the largest receiver operating characteristic (ROC) curve and area under the ROC curve (AUC), with sensitivities of 90.9% and 91.7% and specificities of 86.4% and 72.5%, respectively. Conclusions: The quantitative analysis of CEUS provides a new, simpler, and more accurate method for the differential diagnosis of benign and malignant pelvic masses in clinical practice. The sensitivities and specificities of PId and ASd were higher compared to other parameters from the same patient.

Contrast-enhanced ultrasonography for differential diagnosis of adnexal masses.

Background: Quantitative contrast-enhanced ultrasonography parameters are affected by various factors. We evaluated corrected quantitative contrast enhanced ultrasonography in differentiating benign adnexal tumors from malignant tumors. Methods: Patients with adnexal masses who underwent conventional and contrast-enhanced ultrasonography were included. Contrast-enhanced ultrasonography parameters such as base intensity, arrival time, peak intensity, time to peak intensity, ascending slope, and descending slope were measured. Corrected (time to peak intensity - arrival time) mass/(time to peak intensity - arrival time) uterus and (peak intensity - base intensity) mass/(peak intensity - base intensity) uterus were calculated. Lesions were confirmed by pathologic examination of surgical specimens. Results: This study included 31 patients with 35 adnexal lesions including 20 (57.10%) benign and 15 (42.90%) malignant lesions. The corrected contrast-enhanced ultrasonography quantitative parameters in lesions were statistically different between malignant and benign groups (P<0.05). The optimal cut-off value for (time to peak intensity - arrival time) mass/(time to peak intensity - arrival time) uterus, ascending slope, and (peak intensity - base intensity) mass/(peak intensity - base intensity) uterus, and descending slope for differentiating malignant adnexal masses from benign tumors were 1.05 (area under curve: 0.93, P<0.05), 1.11 (area under curve: 0.83, P<0.05), 0.82 (area under curve: 0.73, P<0.05), and -0.27 (area under curve: 0.66, P=0.16), with sensitivity and specificity of 93.33% and 85.00%, 86.67% and 75.00%, 86.67% and 60.00%, and 54.55% and 66.67%, respectively. Conclusions: Corrected contrast-enhanced ultrasonography parameters provide practical differential diagnosis value of adnexal lesions with high reliability for sonologists.

Discovery and evaluation of chalcone derivatives as novel potential anti-Toxoplasma gondii agents.

Due to numerous side effects of traditional treatments for toxoplasmosis, it is urgent to develop new anti-Toxoplasma agents with high efficiency and low toxicity. In this study, using drug-food-homologous chalcone skeleton as a leading compound, 6 series of chalcone derivatives were designed, synthesized, and almost 1/2 compounds have good anti-Toxoplasma activity in vitro. The quantitative structure-activity relationship model of the anti-Toxoplasma activity of the second batch of compounds was established by random forest method (R2 = 0.9407). The Michael receptor in the molecular skeleton of chalcones plays an important role in improving the activity. Among these compounds, four chalcone derivatives exhibited potent anti-T. gondii activity and low cytotoxicity in vitro. Specifically, three of them (4a, 4c and 5e) effectively inhibited the proliferation of Toxoplasma tachyzoites in vivo. Liver and spleen index and biochemical parameters, such as alanine aminotransferase, aspartate aminotransferase and malondialdehyde were significantly decreased by the three chalcone derivatives, suggesting that they have protective effects on the liver of mice infected with Toxoplasma tachyzoites. Overall, this article provides a series of promising compounds for the development of anti-Toxoplasma agents.

Fetal cardiac geometry and function in pregnancies with well-controlled gestational diabetes mellitus using Fetal HQ.

OBJECTIVE: To determine whether abnormal cardiac shape and ventricular global, transverse, and longitudinal contractility are present in fetuses of women with well-controlled GDM. METHODS: A prospective observational study was performed on 80 fetuses of women with well-controlled GDM and 90 control fetuses. Using Fetal HQ, a new speckle-tracking technique, cardiac shape, global contractility, transverse contractility, and longitudinal contractility were calculated. The number and percentage of fetuses with z score values below 5th or above 95th were computed. RESULTS: Compared with controls, there were no significant differences in the frequency of cardiac geometric abnormalities in GDM fetuses. Despite good glycemic control, 60.0% of fetuses in the well-controlled GDM group had one or more types of global, longitudinal, and transverse contractility abnormalities of one or both ventricles, but more frequent on the right ventricle (RV, 50%). The most frequent abnormality of the RV occurred in the transverse contractility (35%), followed by abnormalities of global contractility (25%), and longitudinal contractility (21.3%), compared with controls. The left ventricle (LV) analysis demonstrated that the percentage of study fetuses with only transverse contractility abnormality (18.8%) was significantly higher. CONCLUSIONS: Despite good glycemic control, abnormal ventricular contractility was present in fetuses of women with GDM, but more frequent in the RV. For both the RV and LV, transverse ventricular contractility abnormality were more prevalent than abnormal global and longitudinal contractility. Fetuses of women with GDM should be evaluated for ventricular contractility abnormality and have more follow-ups despite good glycemic control.

Association between formaldehyde exposure and miscarriage in Chinese women.

The aim of this study was to assess whether higher plasma formaldehyde concentration existed in women diagnosed with miscarriage and whether it contributed to higher risk of miscarriage in Chinese women.A case-control study was conducted in 118 women with a diagnosed miscarriage at the first trimester and 191 healthy women who delivered at term. Plasma levels of formaldehyde were measured by gas chromatography in conjunction with mass spectrometry after derivatization of the formaldehyde to the pentafluorophenylhydrazone and characteristics of the subjects including age, education level, occupation, family income, home decoration status, and exposure to second-hand smoke were recorded. Logistic regression analyses were performed to investigate the relationship between miscarriage and levels of formaldehyde.Women with miscarriage were comparable to controls in terms of age, education level, occupation, family income, and home decoration status. They were, however, more likely to be exposed to second-hand smoke. Plasma levels of formaldehyde were significantly higher in women with miscarriage (0.0944 ±â€Š0.0105 vs. 0.0239 ±â€Š0.0032 µg/mL, P < .001). Multivariate logistic regression showed that higher level of formaldehyde (odds ratio [OR]: 8.06, 95% confidence interval [CI]: 4.96-13.09) and exposure to second-hand smoke (OR: 3.60, 95% CI: 1.58-8.20) were independently and significantly associated with higher risk of miscarriage.Plasma levels of formaldehyde were significantly higher in women who were diagnosed with miscarriage than those who delivered at term and higher levels of formaldehyde was an independent risk factor for miscarriage, with higher levels being associated with higher risk of miscarriage.