On the Investigation of Biological Phenomena through Computational Intelligence

This paper is largely devoted for building a novel approach which is able to explain biological phenomena like splicing promoter gene identification disease and disorder identification and to acquire and exploit biological data This paper also presents an overview on the artificial neural network based computational intelligence technique to infer and analyze biological information from wide spectrum of complex problems Bioinformatics and computational intelligence are new research area which integrates many core subjects such as chemistry biology medical science mathematics computer and information science Since most of the problems in bioinformatics are inherently hard ill defined and possesses overlapping boundaries Neural networks have proved to be effective in solving those problems where conventional com-putation tools failed to provide solution Our experiments demonstrate the endeavor of biological phenomena as an effec-tive description for many intelligent applications Having a computational tool to predict genes and other meaningful in-formation is therefore of great value and can save a lot of expensive and time consuming experiments for biologists This paper will focus on issues related to design methodology comprising neural network to analyze biological information and investigate them for powerful application

Expectant management of severe preeclampsia in mid-trimester: a hospital based study

Background: Objective of current study was to determine the maternal and perinatal outcome of the expectant management of severe preeclampsia between 24 weeks and 34 weeks of gestation.Methods: Data was collected from the 50 case notes of the mothers who had expectant management of severe preeclampsia. The study period was April 2011-March 2013. Total of 27 women in the year 2011-2012 (April-March) and 23 women in the year 2012-2013 (April-March) were included. Maternal condition was carefully monitored with the help of non-invasive monitors. Fetal condition was monitored by ultrasound and colour Doppler. Number of days as pregnancy prolongation and maternal and perinatal morbidities were calculated and analysed.Results: The number of days prolonged has been maximum in gestational age of 28-30 weeks, median being 23.5. There is association between higher maternal DBP and appearance of maternal complications (as DBP increases mother is more at risk).Conclusions: Pregnancies complicated by severe preeclampsia can be managed expectantly in a tertiary care centre of India (low resource country) provided mother and fetus are monitored for their wellbeing

Assessment of the dual role of Lyonia ovalifolia (Wall.) Drude in inhibiting AGEs and enhancing GLUT4 translocation through LC-ESI-QTOF-MS/MS determination and in silico studies

Introduction: Diabetes mellitus (DM) is a metabolic disorder that results in glucose accumulation in the blood, accompanied by the production of advanced glycation end products (AGEs) through glycation of cellular proteins. These AGEs interfere with insulin signaling and prevent GLUT4 membrane translocation, thereby promoting the accumulation of more glucose in the blood and causing post-diabetic complications.Methods: In this study, we examine the anti-diabetic potential of Lyonia ovalifolia (Wall.) Drude, a well-known ethnomedicinal plant of the Indian Himalayas. Considering its various medicinal properties, we analyzed its ethanolic extract and various solvent fractions for in vitro antiglycation activity and antidiabetic potential, i.e., stimulation of GLUT4 translocation.Result and Discussions: The results showed that the extract and fractions exhibited increased antiglycation activity and an increased level of GLUT4 translocation. Analysis of a further 12 bioactive compounds of ethanolic extract, identified through LC-ESI-QTOF-MS/MS, revealed the presence of three new compounds: leucothol B, rhodoterpenoids A, and leucothol A. Moreover, we performed molecular docking of identified compounds against key proteins of diabetes mellitus: the sirtuin family of NAD (+)-dependent protein deacetylases 6 (SIRT6), aldose reductase (AR), and tyrosine kinase (TK). The results showed that flavonoid luteolin showed the best binding affinity ((−12.3 kcal/mol), followed by eriodictyol, astilbin, and syringaresinol. An ADMET study showed that luteolin, eriodictyol, astilbin, and syringaresinol may be promising drug candidates belonging to the flavonoid class of compounds, with no harmful effects and complying with all the drug-likeness guidelines. Furthermore, molecular dynamics (MD) simulations on a 50 ns timescale revealed that AR protein was most stable with luteolin throughout the simulation period. Therefore, this study reveals for the first time that L. ovalifolia plays an important role in insulin homeostasis, as shown in in vitro and in silico studies

Risk Stratification of Foetuses based on Estimated Foetal Weight less than the 40th Percentile and Evaluation of Perinatal Outcomes using Third-trimester Obstetric Ultrasound: A Prospective Cohort Study

Introduction: Perinatal mortality and morbidities constitute a burden on society and healthcare system. One of the major identifiable causes of these conditions in India is Low Birth Weight (LBW) and preterm births. Small for Gestational Age (SGA) infants account for almost 46.9% of LBW infants. They are prone to the morbidities of preterm birth and are the second major contributor to perinatal mortality. Recent studies have reported that higher screening performance for SGA can be achieved through ultrasonographic foetal biometry and Doppler studies during the third trimester. Aim: To stratify foetuses with Estimated Foetal Weight (EFW) below the 40th centile, as determined by obstetric ultrasound, into three categories (low, intermediate, and high-risk), and study the perinatal outcomes in each category. Materials and Methods: The present prospective cohort study was conducted in the Department of Obstetrics and Gynaecology at Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India from November 2020 to April 2022. A total of 280 antenatal women, at a gestational period between 35 to 36+6 weeks with singleton pregnancies, were studied and based on the foetal biometry and Doppler parameters, women were classified into low (Group A), intermediate (Group B) and high risk (Group C) categories. Risk categorisation was based on EFW and Doppler indices. The low-risk group underwent an ultrasound Doppler scan after four weeks, the intermediate-risk group after two weeks, and the high-risk group was scanned weekly. The high-risk group was delivered at 39 weeks of gestation. Perinatal outcomes, neonatal weights, adverse neonatal outcomes {such as Neonatal Intensive Care Unit (NICU) admissions exceeding 48 hours}, stillbirths, and neonatal deaths were recorded. The Area under Curve (AUC) cut-off for EFW percentiles on ultrasonography was calculated as a predictor for SGA foetuses requiring NICU admissions. Concurrent admissions in the NICU of neonates delivered to unregistered pregnant mothers, who were not screened during the antenatal period, were also recorded. The Chi-square test was used to compare categorical data between groups. The receiver operating characteristic curve was used to determine the cut-off for foetal weight to predict NICU admission. A p-value of <0.05 was considered statistically significant. Results: Among the study population, 231 (82.6%) were between 21-30 years of age, and 250 (88.87%) had a normal Body Mass Index (BMI) with a mean age of 25.78±3.90 years. On risk categorisation, 71 (25.1%), 82 (29%), and 127 (45.9%) women were in the high, intermediate, and low-risk categories, respectively. All the neonates in the high-risk group were classified as SGA according to the INTERGROWTH 21st growth chart. Among the neonates, 18 (6.4%) weighed below 2100 g, 35 (12.4%) weighed between 2101 to 2200 g, 62 (22.3%) weighed between 2201 to 2400 g, and 165 (59%) weighed above 2401 g. NICU admissions occurred in 25 (35.2%), 10 (12%), and 5 (3.8%) neonates in the high, intermediate, and low-risk groups, respectively (p-value < 0.001). At a cut-off of EFW (g) less than or equal to 2122 g (between the 10th and 20th centile) during the first ultrasound, it predicted SGA neonates requiring NICU admissions with a sensitivity of 80% and a specificity of 70%. No stillbirths or neonatal mortality occurred in the study group. Conclusion: A single third-trimester obstetric ultrasound, along with Doppler measurements, should be performed at 35 to 36 weeks as an important adjunct for identifying and stratifying the risk of singleton foetuses. Close monitoring and timely delivery can help reduce adverse perinatal outcomes in SGA foetuses

Tinosporaside from <i>Tinospora cordifolia</i> Encourages Skeletal Muscle Glucose Transport through Both PI-3-Kinase- and AMPK-Dependent Mechanisms

The stem of Tinospora cordifolia has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated from the stem of T. cordifolia, was investigated for its effects on glucose utilization in skeletal muscle cells, which was followed by determining the anti-hyperglycemic efficacy in our diabetic db/db mice model. We found that tinosporaside augmented glucose uptake by increasing the translocation of GLUT4 to the plasma membrane in L6 myotubes, upon prolonged exposure for 16 h. Moreover, tinosporaside treatment significantly increased the phosphorylation of protein kinase B/AKT (Ser-473) and 5′ AMP-activated protein kinase (AMPK, Thr-172). These effects were abolished in the presence of the wortmannin and compound C. Administration of tinosporaside to db/db mice improved glucose tolerance and peripheral insulin sensitivity associated with increased gene expression and phosphorylation of the markers of phosphoinositide 3-kinases (PI3Ks) and AMPK signaling in skeletal muscle tissue. The findings revealed that tinosporaside exerted its antidiabetic efficacy by enhancing the rate of glucose utilization in skeletal muscle, mediated by PI3K- and AMPK-dependent signaling mechanisms

Vitamin B6 Tethered Endosomal pH Responsive Lipid Nanoparticles for Triggered Intracellular Release of Doxorubicin

This study reports the development of Vitamin B6 (VitB6) modified pH sensitive charge reversal nanoparticles for efficient intracellular delivery of Doxorubicin (DOX). Herein, VitB6 was conjugated to stearic acid, and the nanoparticles of the lipid were formulated by solvent injection method (DOX-B6-SA-NP). Because of the p<i>K</i>_a (5.6) of VitB6, DOX-B6-SA-NP showed positive charge and enhanced release of DOX at pH 5. Confocal microscopy illustrated that DOX-B6-SA-NP treatment kept higher DOX accumulation inside the cells than conventional pH insensitive lipid nanoparticles (DOX-SA-NP). The cationic charge of nanoparticles subsequently facilitated the endosomal escape and promoted the nuclear accumulation of DOX. Furthermore, in vitro cytotoxicity, apoptosis, cell cycle arrest, and mitochondrial membrane depolarization studies supported the enhanced efficacy of DOX-B6-SA-NP in comparison to free DOX and DOX-SA-NP. Intravenous pharmacokinetics and biodistribution investigations indicated that pH sensitive nanoparticles can significantly prolong the blood circulation time of DOX in biological system and increase the drug accumulation to tumor site. Consequent to this, DOX-B6-SA-NP also exhibited much enhanced therapeutic efficacy and lower toxicity in tumor-bearing rats compared to free DOX. The reduction in toxicity was confirmed by histological and survival analysis. In conclusion, these results suggest that the VitB6 modified charge reversal nanoparticles can be a novel platform for the successful delivery of anticancer drugs

Naturally Occurring Carbazole Alkaloids from <i>Murraya koenigii</i> as Potential Antidiabetic Agents

This study identified koenidine (<b>4</b>) as a metabolically stable antidiabetic compound, when evaluated in a rodent type 2 model (leptin receptor-deficient <i>db/db</i> mice), and showed a considerable reduction in the postprandial blood glucose profile with an improvement in insulin sensitivity. Biological studies were directed from the preliminary in vitro evaluation of the effects of isolated carbazole alkaloids (<b>1</b>–<b>6</b>) on glucose uptake and GLUT4 translocation in L6-GLUT4<i>myc</i> myotubes, followed by an investigation of their activity (<b>2</b>–<b>5</b>) in streptozotocin-induced diabetic rats. The effect of koenidine (<b>4</b>) on GLUT4 translocation was mediated by the AKT-dependent signaling pathway in L6-GLUT4<i>myc</i> myotubes. Moreover, in vivo pharmacokinetic studies of compounds <b>2</b> and <b>4</b> clearly showed that compound <b>4</b> was 2.7 times more bioavailable than compound <b>2</b>, resulting in a superior in vivo efficacy. Therefore, these studies suggested that koenidine (<b>4</b>) may serve as a promising lead natural scaffold for managing insulin resistance and diabetes