Evaluation of anti-tumor activity of ethanolic extract of Glycyrrhiza glabra against Ehrlich ascites carcinoma in swiss albino mice

Background: Cancer is one of the most life threatening diseases which is in need of newer drug development. The use of plant products with potent antioxidant and cytotoxic activity is upcoming Studies reveal that herbal product have increased efficacy as well as decreased side effects, with this in mind the present study was undertaken to assess the antitumor activity of extracts of Glycyrrhiza glabra (GG) against ehrlich ascites carcinoma in swiss albino mice.Methods: The extracts of roots of GG was collected and acute toxicity study was done following which the antitumor effect of extracts of GG was assessed by change in the body weight, mean survival time (MST), and percentage increased life span (% ILS). MST of each group containing six mice was monitored by recording the mortality daily for 6 weeks and % ILS was calculated. The hematological parameters and biochemical assays were also measured.Results: Extracts of GG showed a significant reduction in % increase in tumor induced body weight of the mice. The % increase in life span was also significant in the higher dose of GG (500 mg/kg). The combination of GG with standard drug cisplatin had better efficacy in terms of % ILS, hematological and biochemical parameters. The results obtained were statistically significant.Conclusions: The antitumor activity studies measuring the viability of cancer cells when exposed to the ethanolic extract of Glycyrrhiza glabra showed a potent cell-killing effect, indicating the presence of anti-cancer principles in the preparation

Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR

Biology of urothelial tumorigenesis: insights from genetically engineered mice

Urothelium, one of the slowest cycling epithelia in the body, embodies a unique biological context for cellular transformation. Introduction of oncogenes into or removing tumor suppressor genes from the urothelial cells or a combination of both using the transgenic and/or knockout mouse approaches has provided useful insights into the molecular mechanisms of urothelial transformation and tumorigenesis. It is becoming increasingly clear that over-activation of the receptor tyrosine kinase (RTK) pathway, as exemplified by the constitutively activated Ha-ras oncogene, is both necessary and sufficient to initiate the low-grade, non-invasive urothelial carcinomas. Dosage of the mutated Ha-ras, but not concurrent inactivation of pro-senescence molecules p16Ink4a and p19Arf, dictates whether and when the low-grade urothelial carcinomas arise. Inactivation of both p53 and pRb, a prevailing paradigm previously proposed for muscle-invasive urothelial tumorigenesis, is found to be necessary but insufficient to initiate this urothelial carcinoma variant. Instead, downregulation in p53/pRb co-deficient urothelial cells of p107, a pRb family member, is associated with the genesis of the muscle-invasive bladder cancers. p53 deficiency also seems to be capable of cooperating with that of PTEN in eliciting invasive urothelial carcinomas. The genetically engineered mice have improved the molecular definition of the divergent pathways of urothelial tumorigenesis and progression, helped delineate the intricate crosstalk among different genetic alterations within a urothelium-specific context, identified new prognostic markers and novel therapeutic targets potentially applicable for clinical intervention, and provided in vivo platforms for testing preventive strategies of bladder cancer

Phytochemical fractions from Annona muricata seeds and fruit pulp inhibited the growth of breast cancer cells through cell cycle arrest at G(0)/G(1) phase

Introduction: Annona muricata (L.) (AM), commonly known as Soursop and Lakshmanaphala/Hanumaphala in India, has been extensively used in ethnomedicine for treating tuberculosis, urinary tract infections (UTIs) and cancers. The fruit is a rich source of antioxidants and antitumor agents. Methods: In this study, we have extracted phytochemicals that exhibited anti-cancer property from the (a) fruit pulp using methanol (AMPM) and water (AMPW); and (b) seeds using methanol (AMSM). Qualitative phytochemical analysis showed the presence of phenolics, tannins, alkaloids, flavonoids, sterols, terpenoids, carbohydrates and proteins in AMPM and AMPW. All three extracts were first checked for in vitro antioxidant and anti-inflammatory properties and then tested for efficacy against MCF-7 and MDA-MB-231. Results: Among these three extracts, AMSM showed the highest antioxidant power as well as similar to 80% inhibition at 320 mu g/ml concentration in both cell lines upon treatment for 24h. However, only about 40% inhibition was observed with 320 mu g/ml AMPM treatment, despite its highest anti-inflammatory potential. Water extract AMPW exhibited about 80% growth inhibition at 50% dilution. Since fruit pulp is the one consumed, the extracts AMPM and AMPW were further tested for apoptosis induction and cell cycle arrest. Analysis of the data showed increased apoptosis and G0/G1 cell cycle arrest upon exposure to AMPM and AMPW

The Utility of Salivary Heme to Stratify Healthy Volunteers from Individuals with Gingivitis and Periodontitis: a Pilot Study

Gingival bleeding due to poor oral hygiene is reported globally. Assessment of blood in saliva may improve diagnostics, serve as an outcome measure in clinical trials and support patient education through point-of-care tests. This work analyzed salivary heme using a rapid test format and separately using a lateral flow immunoassay assay [LF] for chair-side implementation. Clinical examinations stratified adult subjects into healthy, gingivitis or periodontitis groups at baseline. Healthy subjects presented no periodontal pockets and whole mouth gingivitis scores of less than 1.0.  Gingivitis subjects registered gingival index scores greater than 1.0.  Included in the periodontal disease group were subjects with periodontal pockets greater than 4 mm.  The rapid test is based on the peroxidase activity salivary heme converting a colourless probe to a coloured compound for spectrophotometric analysis.  For the LF assay, saliva was placed in the test window of the device with reactions scored after room temperature incubation.  Average salivary heme concentrations in the healthy, gingivitis and periodontal disease groups were 27, 201 and 326 nM respectively, by the rapid test, representing significant differences by analysis of variance and Tukey’s-multiple comparison tests (p<0.05).  Similarly, results in the LF assay demonstrated increasing band intensity from the healthy to the periodontal disease groups and was quantifiable by image analysis.   This pilot study emphasizes the potential efficacy of rapid heme measurement in investigations of oral health

Serum levels of IL-10, IL-17F and IL-33 in patients with asthma: A case-control study

Objectives: The development of inflammation in asthma involves an intricate network of cytokines that recruit and activate numerous immune cells. This study was aimed to compare serum levels of IL-10, IL-17F, and IL-33 in asthmatic patients and non-asthmatic controls and correlate cytokine levels to asthma severity and various clinical, spirometric, and laboratory variables. Methods: Using ELISA, serum levels of IL-10, IL-17F, and IL-33 were evaluated in 44 asthmatics (14 mild persistent, 15 moderate persistent, and 15 severe persistent) and 44 controls. Results: This is one of the first reports showing a significant difference in serum levels of asthma-associated cytokines, anti-inflammatory IL-10, and pro-inflammatory IL-17F and IL-33, in the same subset of asthmatic patients. Our results showed diminished level of IL-10 and elevated levels of IL-17F and IL-33 in asthmatics than in controls (p\textless0.001). Assessment of cytokine levels between subjects of different gender, age group, and BMI showed non-significant differences. Correlation analysis of cytokine levels to clinical variables showed that IL-17F is associated negatively to FVC % predicted (forced vital capacity) and FEV1% predicted (forced expiratory volume in one second) and positively to number of allergens sensitized and FEV1 reversibility. A strong negative correlation was found between IL-10 and IL-33 levels (p=0.001). Conclusions: Negative correlation between IL-10 and IL-33 levels may reflect a converse relationship between anti-inflammatory and pro-inflammatory cytokines in an individually balanced pattern. The association between IL-17F level and asthmatic phenotypes such as reduced FVC and FEV1, higher degree of sensitization, and post-bronchodilator reversibility needs further assessments

Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma

Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. Objective: To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. Methodology: The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. Results: We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p 0.5) was observed with IL-6 and MMP-9 levels and FEV1 improvement after 2 months of ICS+LABA. Conclusion: Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions

Providing Diabetes Education through Phone Calls Assisted in the Better Control of Hyperglycemia and Improved the Knowledge of Patients on Diabetes Management

Purpose: A recent single-arm pilot study from our group showed a significant decrease in HbA1C in Type-2 diabetes individuals provided with SMS and phone call-based education on glycemic control. Considering the preference of participants to phone call-based education, a randomized control trial (RCT) with parallel design was conducted to determine the impact of phone call-based diabetes educational intervention on the control of hyperglycemia and improvement in the knowledge about diabetes management. Objectives: To determine the impact of phone call-based educational intervention on the control of hyperglycemia and improvement in the knowledge about diabetes management. Methodology: The study was conducted for a period of 12 months on a total of 273 Type-2 diabetic patients (interventional group (n = 135); non-interventional group (n = 138)) who had provided consent to participate. Subjects in the case group received weekly phone calls on diabetes education; whereas the control group received no education. HbA1C investigations were carried out at baseline and at every fourth month until the completion of the study period for the subjects in both the groups. The impact of phone call-based education was measured by comparing HbA1C values as well as by measuring the questionnaire-based knowledge scores on diabetes management. Results: At the end of the study period, there was a significant reduction in HbA1C in 58.8% participants (n = 65) and a manifold (2–5-fold) increase in knowledge on diabetes management among participants in the case group (n = 110). However, no significant difference in HbA1C and knowledge score was observed in participants from the control group (n = 115). Conclusion: Phone call-based diabetes education is a viable option to empower patients for better management of Type-2 diabetes

Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma

Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. Objective: To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. Methodology: The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. Results: We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p 0.5) was observed with IL-6 and MMP-9 levels and FEV1 improvement after 2 months of ICS+LABA. Conclusion: Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions