Mutagenic activity of oxathiolane steroids: structural requirement for the genotoxic activity in Salmonella and E. coli.

Oxathiolanes and disulfonyl derivatives of steroids were tested for mutagenic activity in the Ames tester strains. The test compounds exhibited mutagenic activity without metabolic activation although metabolic activation markedly enhanced their activity. A significant decrease in the survival of the radiation-sensitive mutants recA, lexA and rer of E. coli was observed as compared to their wild-type counterpart in the presence of the test steroid. Structural features which appear to be crucial for the mutagenic activity in these steroidal drugs are: (i) an electron-donating group at position 3, and (ii) a bulky group anchored at the 5th and 6th positions. The test steroids appear to damage DNA which in turn initiates the SOS repair with the concomitant induction of mutation.     

The Association of Vitamin D Receptor Polymorphisms with Multiple Sclerosis in a Case-Control Study from Kuwait

Vitamin D deficiency is associated with several diseases including multiple sclerosis (MS). Several factors influence vitamin D levels and its optimal multi-function maintenance. Our objective was to assess quantifiable variables influencing vitamin D level and metabolism in MS patients from Kuwait. In a case-control study involving 50 MS patients, and 50 healthy control individuals for which plasma vitamin D levels, supplement use, vitamin D receptor (VDR) variants, and skin pigmentation indices were ascertained; we found overall vitamin D levels to be deficient in both groups, and supplement use to be common practice. VDR variants TaqI and BsmI associated with MS risk, and ApaI associated with low disease progression. VDR variant FokI associated with higher vitamin D levels in both groups. We conclude that several quantifiable variables related to vitamin D associate with MS suggesting a possible clinical immuno-modulatory application of vitamin D for MS patients in Kuwait.     

Intermediate Megavoltage Photon Beams for Improved Lung Cancer Treatments

The goal of this study is to evaluate the effects of intermediate megavoltage (3-MV) photon beams on SBRT lung cancer treatments. To start with, a 3-MV virtual beam was commissioned on a commercial treatment planning system based on Monte Carlo simulations. Three optimized plans (6-MV, 3-MV and dual energy of 3- and 6-MV) were generated for 31 lung cancer patients with identical beam configuration and optimization constraints for each patient. Dosimetric metrics were evaluated and compared among the three plans. Overall, planned dose conformity was comparable among three plans for all 31 patients. For 21 thin patients with average short effective path length (< 10 cm), the 3-MV plans showed better target coverage and homogeneity with dose spillage index R_50% = 4.68±0.83 and homogeneity index = 1.26±0.06, as compared to 4.95±1.01 and 1.31±0.08 in the 6-MV plans (p < 0.001). Correspondingly, the average/maximum reductions of lung volumes receiving 20 Gy (V_20Gy), 5 Gy (V_5Gy), and mean lung dose (MLD) were 7%/20%, 9%/30% and 5%/10%, respectively in the 3-MV plans (p < 0.05). The doses to 5% volumes of the cord, esophagus, trachea and heart were reduced by 9.0%, 10.6%, 11.4% and 7.4%, respectively (p < 0.05). For 10 thick patients, dual energy plans can bring dosimetric benefits with comparable target coverage, integral dose and reduced dose to the critical structures, as compared to the 6-MV plans. In conclusion, our study indicated that 3-MV photon beams have potential dosimetric benefits in treating lung tumors in terms of improved tumor coverage and reduced doses to the adjacent critical structures, in comparison to 6-MV photon beams. Intermediate megavoltage photon beams (< 6-MV) may be considered and added into current treatment approaches to reduce the adjacent normal tissue doses while maintaining sufficient tumor dose coverage in lung cancer radiotherapy.     

Biomarkers for human radiation exposure

There is a concern over the potential use of radioactive isotopes as a weapon of terror. The detonation of a radiation dispersal device, the so-called “dirty bomb” can lead to public panic. In order to estimate risks associated with radiation exposure, it is important to understand the biological effects of radiation exposure. Based on this knowledge, biomarkers to monitor potentially exposed populations after a radiological accident can be developed and would be extremely valuable for emergency response. While the traditional radiation exposure biomarkers based on cytogenetic assays serve as standard, the development of rapid and noninvasive tests for radiation exposure is needed. The genomics based knowledge is providing new avenues for investigation. The examination of gene expression after ionizing radiation exposure could serve as a potential molecular marker for biodosimetry. Microarray based studies are identifying new radiation responsive genes that could potentially be used as biomarkers of human exposure to radiation after an accident.     

Genetic improvement of peanut (Arachis hypogea L.) genotypes by developing short duration hybrids

Peanut, the only cash crop of rainfed areas of Pakistan, is facing immense challenges due to global warming. Climatic factors particularly the temperature fluctuations and rain pattern shift significantly impact the production and yield of peanut and unavailability of resilient varieties exacerbate this impact. To deal with the cropping pattern change and yield losses, due to climate vagaries, a study was conducted to develop early maturing hybrids using line into tester mating design. The F₁ hybrids from the parental lines were produced in the year 2018 using Line × Tester mating design and then grown in the field in the year 2019 for further evaluation. The hybrids were evaluated based on the early maturity and yield-related attributes in comparison with the parental lines. Based on the general combining ability estimate, line V-3 (Golden), was found as best parent with highly significant values for plant height, days to peg formation, days to maturity, number of pegs per plant, number of pods per plants, number of seeds per plant, 100 pod weight 100 seed weight. Similarly, tester V-7 (PI 635006 01 SD) showed highly significant results of GCA for days to germination, day to 50% flowering, plant height, days to peg formation, days to maturity, number of pegs per plant, number of pods per plants, number of seeds per plant, 100 kernel weight, shelling percentage. All the combinations were evaluated for specific combining ability and significant results were observed for V-3 × V-4 (Golden × PI 619175 01 SD) and V-1 × V-6 (BARI-2000 × PI 564846 01 SD) by developing or maturity and yield-related attributes. The hybrid combinations V-3 × V-5 (Golden × PI 635006 01 SD) followed by V-3 × V-6 showed highly significant results for mid parent heterosis and better parent heterosis for days to 50% flowering, plant height, days to peg formation, number of pegs, days to maturity, number of mature seeds per plant, shelling ratio, 100 pod weight and 100 kernel weight. These parents and hybrid combinations with early maturity genes and high yield attributes can further be used for the development of short duration variety.     

Mechanism of rice bran lipase inhibition through fermentation activity of probiotic bacteria

Rice bran oil is known as wonder oil and it is the most important vegetable oil in Asia. Rice bran oil is extracted from bran that is the outer hard layer of rice. It is an emerging category in edible oil with a lot of nutritional properties and health benefits. Rice bran oil is heart-friendly, boosts up immunity, and prevents from other diseases occurring commonly in Pakistan. The current study aimed to stabilize rice bran oil through different probiotic isolates and to assess the nutritional content of rice bran oil after stabilization. The study was aimed to inactivate naturally occurring lipases that can hydrolyze oil into glycerol and free fatty acid which is a serious problem that gives it a rancid taste and smell. Antilipase activity was used to inactivate naturally occurring lipases that are a huge threat to the stabilization process. The fermentation process utilizes antilipase activity without affecting the nutritional value of oil. Lactobacillus strains were used for the stabilization of rice bran oil. Rice bran oil was extracted in the Soxhlet apparatus. The probiotic lab isolates Lactobacillus delbrueckii S2, Lactobacillus casei S5 and Lactobacillus plantarum S13 were applied to it to increase its shelf life and prevent oxidative rancidity. The extraction temperature of rice bran oil was maintained above 40 °C to inhibit lipase activity. Rice bran oil samples were stored at refrigeration temperature to arrest lipase activity. Probiotics maintained acidic pH to keep oil stabilization. Qualitative analysis was done to confirm rice bran oil stabilization. Determination of Free Fatty Acid (FFA) and saponification value confirmed that oxidative rancidity of rice bran oil was controlled by probiotics. FFA count was less than 10% and Saponification Value (SV) was 180. GC analysis was performed to analyze the FFA profile. Gas Chromatography results have shown 3 fatty acids. Statistical analysis has shown non-significant effect on different incubation temperatures of Lactobacillus isolates. Among the biological methods of stabilization, the use of probiotics is a novel concept and recommended for commercial application.     

CXCR7 mediated Giα independent activation of ERK and Akt promotes cell survival and chemotaxis in T cells

Chemokine receptors CXCR7 and CXCR4 bind to the same ligand stromal cell derived factor-1alpha (SDF-1α/CXCL12). We assessed the downstream signaling pathways mediated by CXCL12-CXCR7 interaction in Jurkat T cells. All experiments were carried out after functionally blocking the CXCR4 receptor. CXCL12, on binding CXCR7, induced phosphorylation of extra cellular regulated protein kinases (ERK 1/2) and Akt. Selective inhibition of each signal demonstrated that phosphorylated ERK 1/2 is essential for chemotaxis and survival of T cells whereas activation of Akt promotes only cell survival. Another interesting finding of this study is that CXCL12-CXCR7 interaction under normal physiological conditions does not activate the p38 pathway. Furthermore, we observed that the CXCL12 signaling via CXCR7 is Giα independent. Our findings suggest that CXCR7 promotes cell survival and does not induce cell death in T cells. The CXCL12 signaling via CXCR7 may be crucial in determining the fate of the activated T cells.     

Risk assessment of heavy metal and metalloid toxicity through a contaminated vegetable (Cucurbita maxima) from wastewater irrigated area: A case study for a site-specific risk assessment in Jhang,Pakistan

The present research was conducted in district Jhang, Pakistan, to evaluate the concentration of metals/metalloids in soil and pumpkin (Cucurbita maxima) irrigated with domestic wastewater. Data revealed that the levels of metals and metalloids in soil samples from two different sites were below the safe limits except Cd, whereas, in the vegetable, the concentrations of As, Se, Ni, Mo, Pb, Mn, and Cu were above the safe limits. The levels of 12 metals and metalloids in the soil were ranged between 0.14 to 22.76 mg/kg at site-I and 0.16 to 22.13 mg/kg at site-II. The levels of these metals in the vegetable were found 0.35 to 61.13 mg/kg at site-I and 0.31 to 53.63 mg/kg at site-II. The transfer factor at both sites was highest for As and Co. The pollution load index recorded for Se, Cu, Cd, Mo, Pb, and Co was greater than 1. The daily intake of As, Mn, and Mo was above the oral reference dose, which reflects that the intake of pumpkin is not safe for the inhabitants of the selected sites. The control measures should be taken to phytoextract heavy metals and metalloids from polluted sites so as to reduce the health risks.