Saraca indica

Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy

Strong impact of TGF-β1 gene polymorphisms on breast cancer risk in Indian women: a case-control and population-based study

Introduction: TGF-β1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-β1 signaling in breast cancer progression is well documented. Some TGF-β1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear. Methods: We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-β1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-β1 were measured by ELISA. Results: c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p  =  0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-β1 was significantly elevated in patients in comparison to controls (p<0.001). Conclusion: c.29C>T and c.74G>C polymorphisms in the TGF-β1 gene significantly affect breast cancer risk, which correlates with elevated TGF-β1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations

In vitro physicochemical characterization of nanocarriers: a road to optimization

Today's drug delivery scientists and pharmaceutical technologists own unprecedented variety of characterization techniques at their disposal not only to assign precise numerical values to the particle parameters but also to probe their developmental phases as well as their internal environment. Therefore, mechanistic understanding of structure-function relationships of nanotherapeutic systems seems to be a dynamic avowal considering the optimization of final nanoformulation system intended for biodistribution and targeting. This chapter aims to decipher the key in vitro physicochemical parameters in dry state, liquid state, as well as in both dry and liquid states, with the perspective of nanoparticle technology, and the diverse physical and experimental means in which these parameters can be demarcated. Further, an attempt has been made to introduce some best suited specialized techniques that enable to expand the accessible range of information to gain deeper insights into specific nanoplatform properties

In vitro physicochemical characterization of nanocarriers: a road to optimization

Today's drug delivery scientists and pharmaceutical technologists own unprecedented variety of characterization techniques at their disposal not only to assign precise numerical values to the particle parameters but also to probe their developmental phases as well as their internal environment. Therefore, mechanistic understanding of structure-function relationships of nanotherapeutic systems seems to be a dynamic avowal considering the optimization of final nanoformulation system intended for biodistribution and targeting. This chapter aims to decipher the key in vitro physicochemical parameters in dry state, liquid state, as well as in both dry and liquid states, with the perspective of nanoparticle technology, and the diverse physical and experimental means in which these parameters can be demarcated. Further, an attempt has been made to introduce some best suited specialized techniques that enable to expand the accessible range of information to gain deeper insights into specific nanoplatform properties

Geographic information system-based mapping of air pollution & emergency room visits of patients for acute respiratory symptoms in Delhi, India (March 2018-February 2019)

Background & objectives: Studies assessing the spatial and temporal association of ambient air pollution with emergency room visits of patients having acute respiratory symptoms in Delhi are lacking. Therefore, the present study explored the relationship between spatio-temporal variation of particulate matter (PM)2.5 concentrations and air quality index (AQI) with emergency room (ER) visits of patients having acute respiratory symptoms in Delhi using the geographic information system (GIS) approach. Methods: The daily number of ER visits of patients having acute respiratory symptoms (less than or equal to two weeks) was recorded from the ER of four hospitals of Delhi from March 2018 to February 2019. Daily outdoor PM2.5 concentrations and air quality index (AQI) were obtained from the Delhi Pollution Control Committee. Spatial distribution of patients with acute respiratory symptoms visiting ER, PM2.5 concentrations and AQI were mapped for three seasons of Delhi using ArcGIS software. Results: Of the 70,594 patients screened from ER, 18,063 eligible patients were enrolled in the study. Winter days had poor AQI compared to moderate and satisfactory AQI during summer and monsoon days, respectively. None of the days reported good AQI (<50). During winters, an increase in acute respiratory ER visits of patients was associated with higher PM2.5 concentrations in the highly polluted northwest region of Delhi. In contrast, a lower number of acute respiratory ER visits of patients were seen from the 'moderately polluted' south-west region of Delhi with relatively lower PM2.5 concentrations. Interpretation & conclusions: Acute respiratory ER visits of patients were related to regional PM2.5 concentrations and AQI that differed during the three seasons of Delhi. The present study provides support for identifying the hotspots and implementation of focused, intensive decentralized strategies to control ambient air pollution in worst-affected areas, in addition to the general city-wise strategies

Chemotherapeutic Potential of 2-[Piperidinoethoxyphenyl]-3-Phenyl-2H-Benzo(b)pyran in Estrogen Receptor- Negative Breast Cancer Cells: Action via Prevention of EGFR Activation and Combined Inhibition of PI-3-K/Akt/FOXO and MEK/Erk/AP-1 Pathways

<div><p>Inhibition of epidermal growth factor receptor (EGFR) signaling is considered to be a promising treatment strategy for estrogen receptor (ER)-negative breast tumors. We have investigated here the anti-breast cancer properties of a novel anti-proliferative benzopyran compound namely, 2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzo(b)pyran (CDRI-85/287) in ER- negative and EGFR- overexpressing breast cancer cells. The benzopyran compound selectively inhibited the EGF-induced growth of MDA-MB 231 cells and ER-negative primary breast cancer cell culture. The compound significantly reduced tumor growth in xenograft of MDA-MB 231 cells in nude mice. The compound displayed better binding affinity for EGFR than inhibitor AG1478 as demonstrated by molecular docking studies. CDRI-85/287 significantly inhibited the activation of EGFR and downstream effectors MEK/Erk and PI-3-K/Akt. Subsequent inhibition of AP-1 promoter activity resulted in decreased transcription activation and expression of c-fos and c-jun. Dephosphorylation of downstream effectors FOXO-3a and NF-κB led to increased expression of p27 and decreased expression of cyclin D1 which was responsible for decreased phosphorylation of Rb and prevented the transcription of E2F- dependent genes involved in cell cycle progression from G1/S phase. The compound induced apoptosis via mitochondrial pathway and it also inhibited EGF-induced invasion of MDA-MB 231 cells as evidenced by decreased activity of MMP-9 and expression of CTGF. These results indicate that benzopyran compound CDRI-85/287 could constitute a powerful new chemotherapeutic agent against ER-negative and EGFR over-expressing breast tumors.</p></div

Age dependent associations of genotypes with confounding covariates in north Indian population by Cox regression analysis.

<p>The odds are of BMI “>23 kg/m², Diet “Non vegetarian”, Religion “Hindu”, Family history “Yes”, Personal habits “Yes”, Age at menarche “>14 yrs), Age at 1^st full term pregnancy “>19 yrs” and Menopausal status “Yes” against BMI “≤23 kg/m², Diet “Vegetarian”, Religion “Muslim”, Family history “No”, Personal habits “No”, Age at menarche “≤14 yrs), Age at 1^st full term pregnancy “≤19 yrs” and Menopausal status “No”.</p>*<p>Statistically significant (p<0.001).</p

Analysis of apoptosis in MDA-MB 231 and primary breast adenocarcinoma cells.

<p>(A) Cells treated with vehicle and CDRI-85/287 were analyzed by flow cytometry of annexin-V/PI stained cells after 48h culture. AV⁺/PI⁻ - intact cells; AV⁻/PI⁺ -nonviable/necrotic cells; AV⁺/PI⁻ and AV⁺/PI⁺ - apoptotic cells. Representative images are shown in the upper panel and the percentage of cell fraction with SEM based on three independent experiments is shown in the lower panel. p values are a-p<0.001, b-p<0.01, c-p<0.05 and d-p>0.05 vs. control. (B) Western blot analysis to see the expression of pro- and anti- apoptotic proteins. MDA-MB 231 and primary breast cancer cells were treated with the indicated concentrations of compound for 48h, and 30 µg whole cell lysate in each lane was probed for the expression of different proteins using specific antibodies. β-actin was used as a control to correct for loading. Representative blots are shown in the upper panel and densitometric quantitation of protein expression levels are shown as fold changes in the lower panel. Results are expressed as mean ± SEM, n = 3. p values are a-p<0.001, b<0.01, c-p<0.05 and d-p>0.05 vs. control.</p