Identification of two novel thiophene analogues as inducers of autophagy mediated cell death in breast cancer cells.

Natural compounds isolated from different medicinal plants remain one of the major resources of anticancer drugs due to their enormous chemical diversity. Studies suggested therapeutic potential for various tanshinones, key bioactive lipophilic compounds from the root extracts of Salvia miltiorrhiza Bunge, against multiple cancers including breast carcinoma. We designed, synthesized and evaluated anti-cancer properties of a series of condensed and doubly condensed furophenanthraquinones of tanshinone derivatives on two breast cancer lines - MCF7 and MDA-MB-231. We identified two thiophene analogues - compounds 48 and 52 with greater anti-proliferative efficiency (~4 fold) as compared to the natural tanshinones. Mechanistically, we showed that both compounds induced autophagy mediated cell death and partial but significant restoration of cell death in the presence of autophagy inhibitor further supported this notion. Both compounds transcriptionally activated several autophagy genes responsible for autophagosome formation along with two death regulators - GADD34 and CHOP for inducing cell death. Altogether, our studies provide strong evidence to support compounds 48 and 52 as promising leads for further development as anticancer agents through modulating autophagy mechanism.

Development and validation of the Standing Balance Assessment for Individuals with Spinal Cord Injury (SBASCI) - A new outcome measure.

BACKGROUND: Injury to the spinal cord results in standing balance impairment following variable sensorimotor loss. Standing balance training is a realistic goal for the majority of individuals with spinal cord injury (SCI) for which therapists need valid measures to assess standing ability in people with SCI that are relevant to functionality. OBJECTIVE: The objective of the study was to develop an all inclusive Standing Balance Assessment for Individuals with Spinal Cord Injury (SBASCI) measure and to establish its initial psychometric properties. METHODS: The study was carried out in three phases: Item development, scale development and scale evaluation. Literature review, focus group discussions and evaluation by experts resulted in the development of a 22-item SBASCI scale. The scale was administered on 120 participants with SCI. Exploratory factor analysis and item analysis were used to determine construct validity and internal consistency of the scale. RESULTS: Content validity was established qualitatively and quantitatively. The scale shows high internal consistency reliability (Cronbach's alpha 0.96). The results of the exploratory factor analysis suggested a four factor structure retaining all the 22 items. CONCLUSION: SBASCI is a valid and reliable scale to measure the standing balance of individuals with SCI. Further studies are required to establish other psychometric properties.

Tunable luminescence of a synthesized furophenanthraquinone derivative: interactions with different solvents.

The synthesis is described of a luminescent furophenanthraquinone derivative, 9-methoxyphenanthro[4,3-b]furan-4,5-dione (MPFD). The biological importance of tetracyclic furophenanthraquinones was considered and the tunable luminescence of MPFD in different solvents was studied to explore the nature of the specific interactions between MPFD and solvents. Observation of dual emission bands and identical nature of the fluorescence excitation spectra of MPFD monitored at the emission wavelength in polar solvents indicated the formation of two different types of species in the excited state, probably due to proton transfer from the solvent to MPFD. Luminescence intensity due to anionic species was found to be increased and the corresponding peak was red shifted with increase in the proton-donating ability of the solvents, acting as an acid with respect to MPFD. Availability of more acidic protons in the solvent facilitated this phenomenon occurring in the excited state. MPFD also interacted with halogen-containing solvents by forming electron donor-acceptor charge transfer (CT) complexes. This CT complex formation was dependent on the number of chlorine atoms; the position of the corresponding luminescence band varied with the polarity of the solvent. Extent of the CT increased with increase in the number of chlorine atoms in the dichloro, trichloro and tetrachloro solvents, whereas the luminescence peak due to the CT complex was found to be blue shifted with decrease in solvent polarity. Interaction of the synthesized bioactive MPFD with different solvents deserves biological importance as proton transfer and CT play pivotal roles in biology.

Effects of obesity on balance and gait alterations in young adults.

The effects of obesity on the balance and gait parameters like step width and foot angle (degree of toe out) in young adults were studied. 60 subjects of both the genders were taken. 30 were taken as a control group (non-obese, BMI < 25) and 30 were taken as experimental group (obese, BMI 30 >). Functional Reach Test (FRT) was used for Balance Testing and the Footprint method was used for Gait parameters measurements. The value of functional reach test in females was 11.90 +/- 0.12 inches in control group and 7.01 +/- 1.80 inches in experimental group (t = 5.31, P < 0.001) and in males, it was 16.45 +/- 0.72 inches in control and 11.66 +/- 0.53 inches in experimental group (t = 6.47, P < 0.001). The degree of toe out in females was 6.66 +/- 0.08 degrees for control and 8.13 +/- 0.21 degrees for experimental group (t = 4.08, P < 0.01) and in males, it was 6.59 +/- 0.04 for control and 9.79 +/- 0.51 for experimental group (t = 6.53, P < 0.001). The step width was found to be 4.41 +/- 0.15 inches (control group) and 6.27 +/- 0.35 inches (experimental) in males (t = 4.53, P < 0.01) and it was 3.95 +/- 0.03 inches (control) and 3.42 +/- 1.05 inches (experimental) in females (t = 0.77, P > 0.05). We concluded that obesity has a negative impact on balance of an individual. The degree of toe out was more in obese group as compared to normal BMI group in both genders. The Step Width measurement was more in males of obese group than that in males of normal BMI group but it showed statistically insignificant when compared in females of both groups.

Effect of isometric quadricep activation on "Q" angle in young females.

The Q angle represents an estimate of the resultant force of the quadriceps on the patella and is a predictor of the lateral movement of the patella under dynamic conditions. The aim of the present study was to observe whether isometric quadriceps activation (IQA) can decrease the Q angle and to identify people at high risk of patellar subluxation. Q angles were measured in 23 non impaired young women (22.9 +/- 2.3 years) in relaxed standing and during IQA. There was a significant decrease (4.65 +/- 2.74 degrees) in the Q angle values for subjects with IQA as compared to subjects with measurements in relaxed standing Significance levels were set at P < 0.05. The Q angle decreases with IQA which was highly significant (t = 8.01, P < 0.001). The result supports the view that an excessive Q angle may predispose women to greater lateral displacement of the patella during vigorous activities and sports in which the quadriceps muscle is stressed.