Antioxidant and gastroprotective activities of Andrographis paniculata (Hempedu Bumi) in Sprague Dawley rats

Antioxidant and gastroprotective activities of aqueous and ethanolic extract of Andrographis paniculata leaves in rats have been reported. Sprague Dawley rats, 6 per group were used and rats in groups 1 to 6 were pretreated with (0.25% w/v) carboxymethyl cellulose (negative control, 5 ml/kg), 20 mg/kg omeprazole (positive control), (250 mg/kg and 500 mg/kg) of aqueous leaf extracts (APLAE) and (250 and 500 mg/kg) of ethanol leaf extracts (APLEE) respectively. Animals were orally administered with 95% ethanol (5 ml/kg) 60 min after their pretreatments. Rats were sacrificed 1 h after treatment and gastric contents were collected to measure pH and mucous weight. Stomach was analyzed for gross and histological changes. Ulcer control group showed extensive lesions of gastric mucosal layer, whereas rats pretreated with omeprazole, 250 and 500 mg/kg of APLAE showed significant and dose dependent reduction in gastric lesions with increased pH and mucus content of stomach. Rats pretreated with 250 or 500 mg/kg of APLEE showed significantly better inhibition of gastric mucosal lesions. Further, the in vitro antioxidant studies using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that ethanol extracts have superior free radical scavenging activity with IC50 value = 10.9 than aqueous extracts with IC50 value = 24.65. Results of this study showed that pretreatment with ethonolic extract of A. paniculata ethanolic provided significant protection against gastric ulcer by regulating of pH, mucous production and antioxidant property.     

Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

Histone deacetylases (HDACs) have emerged as important targets for cancer treatment. HDAC-inhibitors (HDACis) are well tolerated in patients and have been approved for the treatment of patients with cutaneous T-cell lymphoma (CTCL). To improve the clinical benefit of HDACis in solid tumors, combination strategies with HDACis could be employed. In this study, we applied Analysis of Functional Annotation (AFA) to provide a comprehensive list of genes and pathways affected upon HDACi-treatment in prostate cancer cells. This approach provides an unbiased and objective approach to high throughput data mining. By performing AFA on gene expression data from prostate cancer cell lines DU-145 (an HDACi-sensitive cell line) and PC3 (a relatively HDACi-resistant cell line) treated with HDACis valproic acid or vorinostat, we identified biological processes that are affected by HDACis and are therefore potential treatment targets for combination therapy. Our analysis revealed that HDAC-inhibition resulted among others in upregulation of major histocompatibility complex (MHC) genes and deregulation of the mitotic spindle checkpoint by downregulation of genes involved in mitosis. These findings were confirmed by AFA on publicly available data sets from HDACi-treated prostate cancer cells. In total, we analyzed 375 microarrays with HDACi treated and non-treated (control) prostate cancer cells. All results from this extensive analysis are provided as an online research source (available at the journal’s website and at http://luigimarchionni.org/HDACIs.html). By publishing this data, we aim to enhance our understanding of the cellular changes after HDAC-inhibition, and to identify novel potential combination strategies with HDACis for the treatment of prostate cancer patients.     

Postnatal gestational age estimation via newborn screening analysis: application and potential

ABSTRACT

Introduction: Preterm birth is a major global health concern, contributing to 35% of all neonatal deaths in 2016. Given the importance of accurately ascertaining estimates of preterm birth and in light of current limitations in postnatal gestational age (GA) estimation, novel methods of estimating GA postnatally in the absence of prenatal ultrasound are needed. Previous work has demonstrated the potential for metabolomics to estimate GA by analyzing data captured through routine newborn screening.

Areas covered: Circulating analytes found in newborn blood samples vary by GA. Leveraging newborn screening and demographic data, our group developed an algorithm capable of estimating GA postnatally to within approximately 1 week of ultrasound-validated GA. Since then, we have built on the model by including additional analytes and validating the model’s performance through internal and external validation studies, and through implementation of the model internationally.

Expert opinion: Currently, using metabolomics to estimate GA postnatally holds considerable promise but is limited by issues of cost-effectiveness and resource access in low-income settings. Future work will focus on enhancing the precision of this approach while prioritizing point-of-care testing that is both accessible and acceptable to individuals in low-resource settings.     

Histopathologic correlation of atypical parakeratosis diagnosed on cervicovaginal cytology

OBJECTIVE: To retrospectively examine the histopathologic findings in women with the isolated finding of atypical parakeratosis (PK) on a Pap test. STUDY DESIGN: The cytology files (1999-2001) were searched for cervicovaginal Pap tests interpreted as atypical PK. Cases were included for study only if there was a subsequent cervicovaginal tissue sample within 1 year of the cytologic interpretation and there was no diagnosis of squamous intraepithelial lesion (SIL) within the previous five years. RESULTS: Of 355 patients with atypical PK, 109 (aged 14-69 years, mean 31.5) met the inclusion criteria of the study. The interval between the cytologic interpretation and cervicovaginal tissue examination ranged from 0.5 to 12 months (mean, 2.5). Sixty-one patients underwent both endocervical curettage (ECC) and cervical biopsy (CBx), 20 patients underwent ECC only, 19 patients underwent CBx only, and the remainder underwent other procedures. Histopathologic findings on the tissue samples included: no significant pathologic change but no squamous epithelium present for evaluation (n = 10, 9.2%), benign changes other than hyperkeratosis and/or PK (n = 50, 45.9%), hyperkeratosis and/or PK (n = 8, 7.3%), low grade SIL (n = 33, 30.3%), high grade SIL (n = 6, 5.5%) and invasive squamous cell carcinoma (n = 2, 1.8%). CONCLUSION: The isolated finding of atypical PK on a Pap test correlated with the presence of an underlying SIL or invasive carcinoma in approximately 40% of patients. Of these, 80% had low grade SIL. The cytologic finding of atypical PK warrants further investigation in order to exclude SILs and/or carcinoma. We suggest that atypical PK be routinely included in the category of atypical squamous cells of undetermined significance.