Exploring the role of 4-thiazolidinone derivatives as potential COX-2 inhibitors and free radical scavenging agents

Background: Cyclooxygenase-2 (COX-2) and free radicals has become an important target in the management of various pathological conditions including cancer and inflammation. The pyridine or thiazolidinone has become an emerging scaffold in the drug design and development of COX-2 inhibitors and free radical scavenging agents. 4-Thiazolidinone clubbed pyridine may potentiate each other activity and can emerge as a promising scaffold in the treatment of inflammation/cancer. Methods: The present work reports synthesis and screening of 4-thiazolidinone-pyridine hybrids with substituted arylidene containing electron-donating group at 5th position. The compounds were screened for their in-vivo anti-inflammatory activity using carrageenan-induced rat paw edema. The antioxidant activity of the compounds was determined by the DPPH method. The compounds were also screened for their ADMET properties. Furthermore, the compounds were docked against COX-2 (PDB ID: 3LN1) using AutoDockTools version 4.2.2. Results: The results showed that compounds bearing 2,5 dimethoxy group are found to be active and possessed the highest docking score with value of -8.0. However, the compound-bearing nitro group was found to be carcinogenic while the former ones showed good ADMET properties. The antioxidant of the compounds bearing 2,5 dimethoxy was found to be excellent than other analogues. Conclusions: The 4-thiazolidinone-pyridine hybrids bearing 2,5 dimethoxy group showed good pharmacological and ADMET profile and can emerged as promising COX-2 inhibitor

Implications of tolerance to iron toxicity on root system architecture changes in rice (Oryza sativa L.)

IntroductionToxicity due to excess soil iron (Fe) is a significant concern for rice cultivation in lowland areas with acidic soils. Toxic levels of Fe adversely affect plant growth by disrupting the absorption of essential macronutrients, and by causing cellular damage. To understand the responses to excess Fe, particularly on seedling root system, this study evaluated rice genotypes under varying Fe levels.MethodsSixteen diverse rice genotypes were hydroponically screened under induced Fe levels, ranging from normal to excess. Morphological and root system characteristics were observed. The onset of leaf bronzing was monitored to identify the toxic response to the excess Fe. Additionally, agronomic and root characteristics were measured to classify genotypes into tolerant and sensitive categories by computing a response stability index.ResultsOur results revealed that 460 ppm of Fe in the nutrient solution served as a critical threshold for screening genotypes during the seedling stage. Fe toxicity significantly affected root system traits, emphasizing the consequential impact on aerial biomass and nutrient deprivation. To classify genotypes into tolerant and sensitive categories, leaf bronzing score was used as a major indicator of Fe stress. However, the response stability index provided a robust basis for classification for the growth performance. Apart from the established tolerant varieties, we could identify a previously unrecognized tolerant variety, ILS 12–5 in this study. Some of the popular mega varieties, including BPT 5204 and Pusa 44, were found to be highly sensitive.DiscussionOur findings suggest that root system damage, particularly in root length, surface area, and root volume, is the key factor contributing to the sensitivity responses under Fe toxicity. Tolerant genotypes were found to retain more healthy roots than the sensitive ones. Fe exclusion, by reducing Fe2+ uptake, may be a major mechanism for tolerance among these genotypes. Further field evaluations are necessary to confirm the behavior of identified tolerant and sensitive lines under natural conditions. Insights from the study provide potential scope for enhancement of tolerance through breeding programs as well as throw light on the role root system in conferring tolerance

Optimization of segment size assuring application perceived QoS in healthcare

Advances in the information and communication technology are significant for the improvement of healthcare services especially in rural areas of developing countries. This is also one of the United Nations Millennium Development Goals. In this work, we proposed a ubiquitous healthcare network and computed the optimum transmission segment size for applications needed to guarantee the perceived quality of service. This has been carried out through NS2 based simulation of a state wide area network infrastructure implemented in Himachal Pradesh, a state in the Western Himalayan region of India. The various types of healthcare applications and services have been classified into according to their QoS requirements as per guidelines in ITU report on network performance objectives. The infrastructure specific optimum values of segment size for these classes of applications running on TCP traffic are computed

A rare anomaly of the foot presented as polydactyly

Presence of one or more digit is called as polydactyly and may manifest singly or with other genetic disorders. The frequency of polydactyly varies widely among populations. It can occur as an isolated condition or as a feature of a congenital condition. Polydactyly is a rare condition, but still rare is in form of triple great toes. We describe a case in a 4-year-old child diagnosed as triphalangism foot with no other obvious visible anomaly. Osteoplasty-combined surgery, which was ideal for anatomical reconstruction. In a 16-month follow-up period child recovered very well

<i>In Vitro</i> Matured Oocytes Are More Susceptible than <i>In Vivo</i> Matured Oocytes to Mock ICSI Induced Functional and Genetic Changes

<div><p>Background</p><p>Concerns regarding the safety of ICSI have been intensified recently due to increased risk of birth defects in ICSI born children. Although fertilization rate is significantly higher in ICSI cycles, studies have failed to demonstrate the benefits of ICSI in improving the pregnancy rate. Poor technical skill, and suboptimal <i>in vitro</i> conditions may account for the ICSI results however, there is no report on the effects of oocyte manipulations on the ICSI outcome.</p><p>Objective</p><p>The present study elucidates the influence of mock ICSI on the functional and genetic integrity of the mouse oocytes.</p><p>Methods</p><p>Reactive Oxygen Species (ROS) level, mitochondrial status, and phosphorylation of H2AX were assessed in the <i>in vivo</i> matured and IVM oocytes subjected to mock ICSI.</p><p>Results</p><p>A significant increase in ROS level was observed in both <i>in vivo</i> matured and IVM oocytes subjected to mock ICSI (P<0.05-0.001) whereas unique mitochondrial distribution pattern was found only in IVM oocytes (P<0.01-0.001). Importantly, differential H2AX phosphorylation was observed in both <i>in vivo</i> matured and IVM oocytes subjected to mock ICSI (P <0.001).</p><p>Conclusion</p><p>The data from this study suggests that mock ICSI can alter genetic and functional integrity in oocytes and IVM oocytes are more vulnerable to mock ICSI induced changes.</p></div

Mitochondrial distribution and activity as measured by Rhodamine 123 and JC1 staining of oocytes.

<p>A. Oocytes retrieved from superovulated mice, subjected to mock ICSI were assessed for mitochondrial distribution. The percentage of oocytes displaying uniform (closed bar); and aggregated (grey bar) distribution in standard control (N = 28), ICSI control (N = 49) and ICSI group (N = 36), was determined. B. <i>In vitro</i> matured metaphase II oocytes, subjected to mock ICSI were evaluated for mitochondrial distribution. The percentage of oocytes displaying uniform (closed bar); aggregated (grey bar) and peripheral (open bar) distribution in standard control (N = 33), ICSI control (N = 33) and ICSI group (N = 32), was determined. ^aP <0.05: Uniform distribution pattern in standard control of figure A Vs Standard control in figure B. ^bP < 0.001: Standard control Vs ICSI control. ^cP < 0.01: Standard control Vs ICSI group. ^dP < 0.0001: percentage of oocytes displaying peripheral distribution in ICSI group with other two groups. C. Mitochondrial activity as measured by the JC1 ratio in IVM oocytes in standard control (N = 81); ICSI control (N = 69) and ICSI group (N = 68). Please note that difference were not significant.</p

Effect of mock injection on Reactive oxygen species level in <i>in vivo</i> and <i>in vitro</i> matured murine oocytes assessed using 2′,7′-dichlorodihydrofluorescein diacetate (DCHFDA) staining.

<p>A. Oocytes retrieved from superovulated mice, subjected to mock ICSI were assessed for ROS production. The relative ROS intensity in standard control (N = 19), ICSI control (N = 22) and ICSI group (N = 20), was determined. The error bars represent the corresponding SEM (Mean ± SEM). ^aP <0.05: Standard control Vs ICSI control, ^bP <0.01: Standard control Vs ICSI group, ^cP < 0.001: ICSI control Vs ICSI group. B. <i>In vitro</i> matured metaphase II oocytes, subjected to mock ICSI were assessed for ROS production. The relative ROS intensity in standard control (N = 28), ICSI control (N = 25) and ICSI group (N = 26), was determined (Mean ± SEM). ^dP < 0.001: Standard control Vs ICSI group and ICSI control Vs ICSI group.</p