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Abstract Background Phoenix dactylifera L. has a diverse set of pharmacological properties due to its distinct phytochemical profile. The purpose of this study was to investigate the anticancer potential of Phoenix dactylifera seed extract (PDSE) in human breast cancer MDA-MB-231 and MCF-7 cells, as well as liver cancer HepG2 cells, and to investigate the anticancer efficacy in triple-negative MDA-MB-231 cells, followed by in silico validation of the molecular interaction between active components of PDSE and caspase-3, an apoptosis executioner protein . Methods In this study, human cancer cell lines were cultured and subsequently treated with 10 to 100 μg/mL of PDSE. MTT test was performed to determine the cell viability, MMP was measured using fluorescent probe JC-1, nuclear condensation was determined by Hoechst 33258 dye, Annexin V-FITC & PI staining and cell cycle analysis were evaluated through flow cytometer, and apoptotic markers were detected using western blotting. The bioactive agents in PDSE were identified using high-performance liquid chromatography (HPLC) analysis. The binding affinity was validated using molecular docking tools AutoDock Vina and iGEMDOCK v2.1. Results Cell viability data indicated that PDSE inhibited cell proliferation in both breast cancer cells and liver cancer cells. MDA-MB-231 cells showed maximum growth inhibition with an IC50 value of 85.86 μg/mL for PDSE. However, PDSE did not show any significant toxicity against the normal Vero cell line. PDSE induced MMP loss and formation of apoptotic bodies, enhanced late apoptosis at high doses and arrested cells in the S phase of cell cycle. PDSE activated the enzymatic activity of cleaved caspase-3 and caused the cleavage of poly-ADB ribose polymerase (PARP) protein. PDSE upregulated pro-apoptotic Bax protein markedly but no significant effect on tumor suppressor protein p53, while it downregulated the anti-apoptotic Bcl-2 protein expression. HPLC analysis showed the presence of rutin and quercetin bioactive flavonols in ethanolic extract of PDS. Interestingly, both active components revealed a strong binding interaction with amino acid residues of caspase-3 (PDB ID: 2XYP; Hetero 4-mer - A2B2) protein. Conclusion PDS could serve as a potential medicinal source for apoptotic cell death in human breast cancer cells and, thus, could be used as a promising and crucial candidate in anticancer drug development. This study warrants further in vivo research, followed by clinical investigation.

Abstract Ajwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC–MS) and investigated anticancer effects against MDA-MB-231 cells. LC–MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.

Background: Gallbladder cancer (GBC) is the most frequent biliary tract cancer, with high morbidity and poor prognosis, and shows early metastasis and invasiveness. No reliable biomarkers are available for detection of GBC progression. Aim: To investigate the immunohistochemical expression of Oct-4 and CD133 in malignant and nonneoplastic lesions of gallbladder and to analyze the clinical significance of the expressions related to clinicopathological parameters. Settings and Design: This is a prospective case control study, conducted in medical college background. Materials and Methods: A total of 103 cases of gallbladder were grouped into malignant lesions (n = 48) and nonneoplastic lesions (simple epithelial hyperplasia; n = 35 and chronic cholecystitis; n = 20). All tissue samples were evaluated for expression of Oct-4 and CD133 using immunohistochemistry in an effort to elucidate the correlation between their expressions with clinicopathological parameters. Statistical Analysis: The final score was calculated by multiplying the intensity to the percentage of positive cells. The scores ≥2 were considered as positive. Results: Significant positive correlation of higher expression levels of Oct-4 and CD133 were observed in malignant as compared to nonneoplastic lesions of gallbladder (P < 0.0001). High expression of Oct-4 and CD133 were significantly associated with tumor grading (Oct-4, P = 0.04; CD133, P = 0.02), staging (Oct-4, P = 0.03; CD133, P = 0.02), and liver metastasis (Oct-4, P = 0.01; CD133, P = 0.007). Significantly reduced survival was observed with high expression of Oct-4 (P = 0.002). No significant correction was observed between CD 133 and survival. Conclusion: This study revealed that high expression level of Oct-4 may provide a new insight for the prognosis of the disease in terms of clinical staging and grade.

Background: In the life of a woman, after 40 years of age, onset of menopause occurs during which hormonal imbalances take place. The present study is aimed at finding out cytopathological changes in the cervical epithelium associated with this hormonal disturbance. Materials and Methods: Cervical cancer screening program is in progress under auspices of Era's Lucknow Medical College and Hospital, Lucknow, since May 2013, in the villages of Lucknow West through camp approach. Till September 2017, 140 camps have been organized and 2440 women attending the camp have been cytologically examined. Out of these, 1534 women were perimenopausal, 165 premenopausal, and 441 postmenopausal. The cytopathological changes have been studied in these three categories of women in relation to different predisposing factors to the cervical carcinogenesis. Results: The squamous intraepithelial lesion (SIL) rate was higher with onset of menopause in the premenopausal women. The SIL rate was higher with nulliparity in these women as well as in the postmenopausal women and also with different gynecological symptoms and clinical lesions of the cervix. The SIL changes associated with HPV and HSV were also higher in them. Conclusion: A high SIL rate found with onset of menopause may be the outcome of gradual estrogen withdrawal in the premenopausal women. Hence, cytological evaluation is mandatory in women between 41 and 45 years of age to rule out any occurrence of cervical cytopathology.

Introduction: There is likelihood of development of premalignant changes in the cervix in the teenagers due to early sexual activity. This assumes importance under rural conditions in India where majority of marriage of girls are performed at young age below 20 years. Aim: The present cytological study was carried out in the three cohorts of rural girls- adolescents (16-20 years), young adult girls (21-25 years) and adult women (26-30 years) to see the effect of early increasing sexual exposure. Materials and Methods: The study cases were derived from the cervical cancer screening which is in progress in the rural population of Lucknow, Uttar Pradesh, India. Of the 1185 study cases, 97 were adolescents, 338 young adult girls and remaining 750 were adult women. Results: The Atypical Squamous Cell Changes of Unknown Significance (ASCUS) were found higher in the adolescents than in young adult girls and adult women while Squamous Intraepithelial Lesions of cervix (SIL) rate was almost equal in the three cohorts. Follow-up revealed progression of ASCUS to Low grade SIL (LSIL) almost equal in the three groups while the persistence of SIL was higher in the young adult girls and adult women. The gynaecological symptoms especially vaginal discharge was more common in the last two groups than in adolescents but the SIL rate was higher with all symptoms in the adolescents. The cervical lesions were more common in the young girls and adult women and SIL rate was higher with different cervical lesions. The majority of adolescents were nulliparous with high SIL rate while in the young adult girls and adult women, the SIL incidence showed rising trend with increasing parity. Conclusion: The study highlights the importance of cytological screening of all the rural young girls and adult women specially who reveal cervical lesions or are symptomatic. This will yield large number of pre-cancerous cases, timely treatment of which will check the progression of SIL to malignancy

Introduction: Sexually Transmitted Diseases (STDs) are very common in the sexually active young Indian women particularly in rural areas because of poor genital hygiene. Aim: The present study was carried out to compare the prevalence of different STDs in the urban and rural population of Lucknow, Uttar Pradesh. Materials and Methods: The present prospective observational study was conducted in 2369 rural women attending camps in 126 villages of West Lucknow between May 2013 and March 2017 undergoing cervical cancer screening and in 38,478 urban women attending Gynaecology Outpatient Department (OPD) of KG Medical University, Lucknow, Uttar Pradesh, India, between April 1971 to November 2005 in which the data were collected retrospectively. Statistical analysis was performed with SPSS version 18.0 and the results were subjected to chisquare test. Results: The incidence of Candida albicans was higher in rural women (4.7%) as against 1.1% seen in urban cohorts. The trend was reverse with Trichomonas vaginalis, the incidence being high (2.9%) in the Urban women than 1.0% in the rural group. The viral STDs were rarely seen in both the groups ranging from 0.1% to 0.6%. Association of Squamous Intraepithelial Lesions (SILs) of the cervix with non-viral STDs was more pronounced in rural women than in their urban counterparts while this was very high with viral STDs in both the groups. All the STDs except HSV were commonly seen in younger sexually active women between 21-30 years. Leucorrhoea was commonly associated with all STDs in both groups but the incidence was almost double in rural women. Conclusion: All the STDs examined were commonly seen in younger women between 21-30 years mostly with symptoms of leucorrhoea. Hence, cytological screening is felt mandatory in such women to rule out any STD infection.

Introduction: MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases, including cancer. It has been suggested that, the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression and binding to target mRNA and represents another type of genetic variability, that can contribute to the susceptibility of human cancers. Aim: The present study investigated the genetic variants in premiRNAs (hsa-miRNA-196a2 rs11614913 C/T, hsa-miRNA-499 rs3746444 T/C and hsa-miRNA-146a rs2910164 G/C) for their role in cervical cancer susceptibility. Materials and Methods: The study comprised 164 controls and 184 patients of cervical cancer. The genotypic frequency of miRNA polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. Results: Hsa-miRNA-499 rs3746444 T/C polymorphism showed a statistically significant association with considerable risk for cervical cancer at genotypes (CC, p=0.001, OR=4.801) and variant allele (p