Cytotoxic Imidazolyl-Mesalazine Ester-Based Ru(II) Complexes Reduce Expression of Stemness Genes and Induce Differentiation of Oral Squamous Cell Carcinoma.

The aggressiveness and recurrence of cancer is linked to cancer stem cells (CSCs), but drugs targeting CSCs may not succeed in the clinic due to the lack of a distinct CSC subpopulation. Clinical Pt(II) drugs can increase stemness. We screened 15 RuII or IrIII complexes with mesalazine or 3-aminobenzoate Schiff bases of the general formulas [Ru(p-cym)L]+, [Ru(p-cym)L], and [Ir(Cp*)L]+ (L = L1-L9) and found three complexes (2, 12, and 13) that are active against oral squamous cell carcinoma (OSCC) CSCs. There is a putative oncogenic role of transcription factors (viz. NOTCH1, SOX2, c-MYC) to enhance the stemness. Our work shows that imidazolyl-mesalazine ester-based RuII complexes inhibit growth of CSC-enriched OSCC 3D spheroids at low micromolar doses (2 µM). Complexes 2, 12, and 13 reduce stemness gene expression and induce differentiation markers (Involucrin, CK10) in OSCC 3D cultures. The imidazolyl-mesalazine ester-based RuII complex 13 shows the strongest effect. Downregulating c-MYC suggests that RuII complexes may target c-MYC-driven cancers.

Thresholding of prominent biomarkers of breast cancer on overall survival using classification and regression tree.

BACKGROUND: HER2, ER, PR, and ERBB2 play a vital role in treating breast cancer. These are significant predictive and prognosis biomarkers of breast cancer. OBJECTIVE: We aim to obtain a unique biomarker-specific prediction on overall survival to know their survival and death risk. METHODS: Survival analysis is performed on classified data using Classification and Regression Tree (CART) analysis. Hazard ratio and Confidence Interval are computed using MLE and the Bayesian approach with the CPH model for univariate and multivariable illustrations. Validation of CART is executed with the Brier score, and accuracy and sensitivity are obtained using the k-nn classifier. RESULTS: Utilizing CART analysis, the cut-off value of continuous-valued biomarkers HER2, ER, PR, and ERBB2 are obtained as 14.707, 8.128, 13.153, and 6.884, respectively. Brier score of CART is 0.16 towards validation of methodology. Survival analysis gives a demonstration of the survival estimates with significant statistical strategies. CONCLUSIONS: Patients with breast cancer are at low risk of death, whose HER2 value is below its cut-off value, and ER, PR, and ERBB2 values are greater than their cut-off values. This comparison is with the patient having the opposite side of these cut-off values for the same biomarkers.

Predictors of Breastfeeding Initiation Among Postnatal Mothers at Tertiary Care Center of a Tribal Dominant State in India: A Regression Analysis.

Background Early initiation of breastfeeding (EIBF) is one of the most important predictors for the survival of a child, spacing between two children, and prevention from childhood infections. Breastfeeding plays an important role in reducing child mortality and morbidity but the practice of EIBF globally is way behind the required time for initiation of breastfeeding after delivery. So, we planned to evaluate the early time of initiation of breastfeeding among the postnatal mothers and to determine the predictors of early initiation of breastfeeding in a tertiary hospital setting. Methodology A hospital-based cross-sectional study was conducted in the postnatal ward of Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand for a period of three months (March-May 2017). Our study included 200 postnatal mothers who delivered normal and healthy babies. Mother-infant dyads enrolled in our study were interviewed personally during six hours of the postpartum period. Irrespective of the mode of delivery, all babies born during the study period whose mothers consented to be a part of the study were included. Data collected were entered in MS Excel and analyzed using IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. Results A total of 200 postnatal mothers fulfilling the study criteria were enrolled during the study. Of them, the majority 98 (49%) belonged to the age group 18-25 years. A hundred and twenty-six (63%) of them resided in rural areas, 182 (91%) were housewives, and only 86 (43%) of them had completed secondary education & above. Early initiation of breastfeeding was found to be only 43 (21.5%) among postnatal mothers. Predictors found to be statistically significant with EIBF were mother's residential status [odds ratio (OR): 2.98; 95% confidence interval (CI): 1.25-7.13], educational status of mother (OR: 3.18; 95% CI: 1.12-9.01) mode of delivery of the baby (OR: 8.93; 95% CI: 2.66-30.06) and ante-natal care (ANC) visits (OR: 0.441; 95% CI: 0.311-0.651). Women's age, religion, ethnicity, occupation, type of family, and socioeconomic status displayed no statistically significant relationship with EIBF. Conclusions It is concluded that nearly one-fifth of mothers in the study initiated breastfeeding within one hour of post-delivery. Maternal education, frequent ANC visits, place of residence, and mode of delivery were also associated with EIBF in India. Nursing staff, as well as clinicians, should reinforce the importance of early initiation of breastfeeding by providing proper health education to post-natal beneficiaries.

Histopathological and Ultrastructural Alterations in Some Organs of Oreochromis niloticus Exposed to Glyphosate-based Herbicide, Excel Mera 71.

Oreochromis niloticus was exposed to glyphosate-based herbicide Excel Mera 71 for 30 days under field and laboratory conditions to investigate the histopathological and ultrastructural responses in gill, liver, and kidney. Gill displayed degenerative changes in the pillar cells of gill epithelium, curling of secondary lamella, and appearance of globular structure in laboratory condition under light microscopy. Scanning electron microscopic (SEM) observations revealed loss of microridges, disappearance of normal array of microridges, and damage in stratified epithelial cells under both the conditions, while severe vacuolation and necrosis were prominent under transmission electron microscopic (TEM) study in the laboratory condition. In liver, excess fat deposition and acentric nuclei in the laboratory condition were prominent under light microscopic and SEM study. TEM study showed necrosis in mitochondria, cytoplasmic vacuolation, degeneration in endoplasmic reticulum (ER), and reduced amount of glycogen droplets, but under field condition, lesions were less. Kidney showed fragmented glomerulus, excessive fat deposition, and hypertrophied nuclei under light microscope, while topological study showed shrinkage of glomerulus and degenerative changes under laboratory condition. TEM study also confirmed necrosis in mitochondria, dilation and fragmentation of ER, and appearance of severe vacuolation in the laboratory study, but no significant alterations were observed in field under SEM and TEM study. Therefore, the present study depicts that Excel Mera 71 caused comparatively less pathological lesions under field than laboratory condition, and finally, these responses could be considered as bioindicators for toxicity study in aquatic ecosystem.