Tumor Markers in Differential Diagnosis of Benign Ovarian Masses.

Background: Although there are many benign tumors in the ovarian adnexal area, the four most common types are still luteal cyst, ovarian mature cystic teratoma (OMCT), ovarian endometriosis, and benign epithelial tumors of the ovary. Purpose: This study aimed to examine the correlation between six tumor markers (CEA, AFP, CA125, CA19-9, SCC, HE4) in the differential diagnosis of female adnexal benign masses and assess their diagnostic value. Patients and Methods: In this study, 135 patients with adnexal benign masses were treated in Zhengzhou first people's Hospital from January 2018 to January 2023. 135 patients were divided into four groups: luteal cyst (13.3%), OMCT (42.2%), ovarian endometriosis (23.7%) and benign epithelial tumors of the ovary (including mucinous cystadenoma and serous cystadenoma) in group D. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of each marker and combined detection. Results: The diameter of luteal cysts was significantly smaller than that of benign ovarian tumors (p < 0.001). ROC analysis showed that the combination of AFP, CA125, CA19-9, and SCC had a higher diagnostic rate for luteal cysts (AUC=0.871; sensitivity: 71.8%; specificity: 88.9). The SCC level in OMCT was significantly higher than in other benign ovarian tumors (p=0.007). ROC analysis indicated that the combination of AFP, HE4, and SCC had a higher diagnostic rate for OMCT (AUC=0.753; sensitivity: 65.4%; specificity: 75.4%). The CA125 level in ovarian endometriosis was significantly higher than in other accessory benign tumors (p < 0.001). ROC analysis demonstrated that the combination of AFP, CA125, and CA19-9 had a higher diagnostic rate for ovarian endometriosis (AUC=0.935; sensitivity: 76.7%; specificity: 96.9%). The tumor diameter of benign epithelial tumors of the ovary was significantly larger than that of other benign ovarian tumors (p < 0.001). ROC analysis revealed that the combination of CA125 and CA19-9 had a higher diagnostic rate for benign epithelial tumors of the ovary (AUC=0.792; sensitivity: 64.5%; specificity: 85.7%). Conclusion: The findings of this study demonstrate that the combined use of tumor markers (CEA, AFP, CA125, CA19-9, SCC, and HE4) has value in diagnosing benign ovarian tumors, including luteal cysts, OMCT, ovarian endometriosis, and benign epithelial tumors of the ovary. However, it is important to acknowledge the limitations of this study, which include its single-center nature and the small sample size. Despite these limitations, the results highlight the potential utility of these markers in clinical practice.

Shionone-Targeted Pneumolysin to Ameliorate Acute Lung Injury Induced by Streptococcus pneumoniae In Vivo and In Vitro.

Streptococcus pneumoniae (S. pneumoniae), as a Gram-positive bacterium, can cause severe bacterial pneumonia, and result in high morbidity and mortality in infected people. Meanwhile, isolated drug-resistant S. pneumoniae is growing, which raises concerns about strategies for combatting S. pneumoniae infection. To disturb S. pneumoniae pathogenicity and its drug-resistance, developing novel anti-infective strategies or compounds is urgent. In this study, the anti-infective effect of shionone was explored. A minimum inhibitory concentration (MIC) assay and growth curve determination were performed to evaluate the effect of the tetracyclic triterpenoid compound shionone against S. pneumoniae. Hemolysis tests, western blotting, oligomerization inhibition assays, and molecular docking were carried out to explore the anti-infective mechanism of shionone. Moreover, the protective effect of shionone was also confirmed in a mousepneumonia model. The results showed that the excellent hemolytic inhibitory activity of shionone was observed at less than 8 µg/mL. Meanwhile, shionone could disturb the oligomerization of pneumolysin (PLY) but did not interfere with PLY expression at less than 4 µg/mL. Molecular docking suggested that shionone targeted the ASP-59, ILE-60, THR-57, PHE-344, and ASN-346 amino acid sites to reduce S. pneumoniae pathogenicity. Furthermore, shionone alleviated lung histopathologic injury and decreased lung bacterial colonization in vivo. The above results showed that shionone could bind to the PLY active pocket under the concentrations of 8 µg/mL and neutralize PLY hemolysis activity to reduce S. pneumoniae pathogenicity in vitro and in vivo.

Alnustone inhibits Streptococcus pneumoniae virulence by targeting pneumolysin and sortase A.

Streptococcus pneumoniae (S. pneumoniae) is a major Gram-positive opportunistic pathogen that causes pneumonia, bacteremia, and other fatal infections. This bacterium is responsible for more deaths than any other single pathogen in the world. Inexplicably, these symptoms persist despite the administration of effective antibiotics. Targeting pneumolysin (PLY) and sortase A (SrtA), the major virulence factors of S. pneumoniae, this study uncovered a novel resistance mechanism to S. pneumoniae infection. Using protein phenotype assays, we determined that the small molecule inhibitor alnustone is a potent drug that inhibits both PLY and SrtA. As essential virulence factors of S. pneumoniae, PLY and SrtA play a significant role in the occurrence of infection. Furthermore, evaluation using PLY-mediated hemolysis assay demonstrated alunstone had the potential to interrupt the haemolytic activity of PLY with treatment alunstone (4 µg/ml). Co-incubation of S. pneumoniae D39 SrtA with small-molecule inhibitors decreases cell wall-bound Nan A (pneumococcal-anchored surface protein SrtA), inhibits biofilm formation, and reduces biomass significantly. The protective effect of invasive pneumococcal disease (IPD) on murine S. pneumoniae was demonstrated further. Our study proposes a comprehensive bacteriostatic mechanism for S. pneumoniae and highlights the significant translational potential of targeting both PLY and SrtA to prevent pneumococcal infections. Our findings indicate that the antibacterial strategy of directly targeting PLY and SrtA with alnustone is a promising treatment option for S. pneumoniae and that alnustone is a potent inhibitor of PLY and SrtA.

Paroxetine suppresses reactive microglia-mediated but not lipopolysaccharide-induced inflammatory responses in primary astrocytes.

BACKGROUND: Astrocytes are the most abundant glial cells in a brain that mediate inflammatory responses and provide trophic support for neurons. We have previously disclosed that paroxetine, a common selective serotonin reuptake inhibitor, ameliorates LPS-induced microglia activation. However, it remains elusive for the role of paroxetine in astrocytic responses. METHODS: Isolated primary astrocytes were pretreated with paroxetine and stimulated with different stimuli, lipopolysaccharide (LPS) or microglia conditioned medium pre-activated with LPS (M/Lps). Inflammatory and neurotrophic responses, underlying mechanisms and the impact on neuronal survival were assessed. RESULTS: Paroxetine had no impact on LPS-stimulated iNOS, TNF-α, and IL-1ß expression, but inhibited M/Lps-induced TNF-α and IL-1ß expression in primary astrocytes. Paroxetine suppressed M/Lps- but not LPS-induced activation of NF-κB and had no impact on the activation of MAPKs and STAT3. Incubation with the resulted astrocyte conditioned media caused no change in the viability of SH-SY5Y cells. BDNF and MANF mRNA expressions were upregulated by M/Lps and paroxetine, respectively. However, M/Lps- or LPS-induced extracellular releases of NO, TNF-α, and/or BDNF in astrocytes were in minor amount compared to those by microglia. CONCLUSIONS: Paroxetine ameliorates the reactive microglia-mediated inflammatory responses in astrocytes partially via inhibition of the NF-κB pathway but has no impact on LPS-stimulated astrocyte activation. While the effects of paroxetine on secondary astrocytic responses are not robust compared to its effect on the innate immune responses of microglia, the results together may implicate a therapeutic potential of paroxetine against neuroinflammation-associated neurological disorders such as Parkinson's disease.

Prevalence of Alzheimer's Disease and Parkinson's Disease in China: An Updated Systematical Analysis.

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are two major neurodegenerative diseases worldwide. Demographic aging is in rapid progress in China. Up-to-date estimates of AD and PD prevalence have not been provided. Methods: Studies that reported the prevalence of AD and PD in China were identified via a systematic database search from 1985 to 2018. Meta-analysis, local polynomial regression and autoregressive integrated moving average model were used for analyses. Results: A total of 99 studies were included in the study with populations of 385,312 and 227,228, respectively for AD and PD. The overall prevalence of AD and PD following age standardization was 3.20% [95% confidence interval (CI) = 3.17-3.23] and 1.06% (95% CI = 1.02-1.10), respectively in individuals over 60 years old. The rates increased drastically for every 10-years increment of age. The yearly prevalence of AD was predicted to increase from 3.81 to 6.17% in the next 5 years. Significant differences were observed between genders [male to female odds ratio (OR) for AD = 0.57, 95% CI = 0.51-0.64; OR for PD = 1.25, 95% CI = 1.06-1.46], and between education levels (Illiterate to non-illiterate OR for AD = 2.99, 95% CI = 2.38-3.75), but not between urban and rural settings. Conclusion: Our results provide an updated insight into the epidemiology of AD and PD in China and their associated rates and ratios. The findings may facilitate China policy makers and health professionals mitigate the related health issues.