Unveiling the anti-glioma potential of a marine derivative, Fucoidan: its synergistic cytotoxicity with Temozolomide-an in vitro and in silico experimental study.

Glioma coined as a "butterfly" tumor associated with a dismal prognosis. Marine algal compounds with the richest sources of bioactive components act as significant anti-tumor therapeutics. However, there is a paucity of studies conducted on Fucoidan to enhance the anti-glioma efficacy of Temozolomide. Therefore, the present study aimed to evaluate the synergistic anti-proliferative, anti-inflammatory and pro-apoptotic effects of Fucoidan with Temozolomide in in vitro and in silico experimental setup. The anti-proliferative effects of Temozolomide and Fucoidan were evaluated on C6 glioma cells by MTT and migration assay. Modulation of inflammatory markers and apoptosis induction was affirmed at the morphological and transcriptional level by dual staining and gene expression. Molecular docking (MD) and molecular dynamics simulation (MDS) studies were performed against the targets to rationalize the inhibitory effect. The dual-drug combination significantly reduced the cell viability and migration of glioma cells in a synergistic dose-dependent manner. At the molecular level, the dual-drug combination significantly down-regulated inflammatory genes with a concomitant upregulation of pro-apoptotic marker. In consensus with our in vitro findings, molecular docking and simulation studies revealed that the anti-tumor ligands: Temozolomide, Fucoidan with 5-(3-Methy1-trizeno)-imidazole-4-carboxamide (MTIC), and 4-amino-5-imidazole-carboxamide (AIC) had the potency to bind to the inflammatory proteins at their active sites, mediated by H-bonds and other non-covalent interactions. The dual-drug combinatorial treatment synergistically inhibited the proliferation, migration of glioma cells and promoted apoptosis; conversely with the down-regulation of inflammatory genes. However, pre-clinical experimental evidence is warranted for the possible translation of this combination. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03814-6.

Computational Modeling of Boundary Layer Flashback in a Swirling Stratified Flame Using a LES-Based Non-Adiabatic Tabulated Chemistry Approach.

When operating under lean fuel-air conditions, flame flashback is an operational safety issue in stationary gas turbines. In particular, with the increased use of hydrogen, the propagation of the flame through the boundary layers into the mixing section becomes feasible. Typically, these mixing regions are not designed to hold a high-temperature flame and can lead to catastrophic failure of the gas turbine. Flame flashback along the boundary layers is a competition between chemical reactions in a turbulent flow, where fuel and air are incompletely mixed, and heat loss to the wall that promotes flame quenching. The focus of this work is to develop a comprehensive simulation approach to model boundary layer flashback, accounting for fuel-air stratification and wall heat loss. A large eddy simulation (LES) based framework is used, along with a tabulation-based combustion model. Different approaches to tabulation and the effect of wall heat loss are studied. An experimental flashback configuration is used to understand the predictive accuracy of the models. It is shown that diffusion-flame-based tabulation methods are better suited due to the flashback occurring in relatively low-strain and lean fuel-air mixtures. Further, the flashback is promoted by the formation of features such as flame tongues, which induce negative velocity separated boundary layer flow that promotes upstream flame motion. The wall heat loss alters the strength of these separated flows, which in turn affects the flashback propensity. Comparisons with experimental data for both non-reacting cases that quantify fuel-air mixing and reacting flashback cases are used to demonstrate predictive accuracy.

Genome Editing for Resistance to Insect Pests: An Emerging Tool for Crop Improvement.

Plants are challenged incessantly by several biotic and abiotic stresses during their entire growth period. As with other biotic stress factors, insect pests have also posed serious concerns related to yield losses due to which agricultural productivity is at stake. In plants, trait modification for crop improvement was initiated with breeding approaches followed by genetic engineering. However, stringent regulatory policies for risk assessment and lack of social acceptance for genetically modified crops worldwide have incited researchers toward alternate strategies. Genome engineering or genome editing has emerged as a new breeding technique with the ability to edit the genomes of plants, animals, microbes, and human beings. Several gene editing strategies are being executed with continuous emergence of variants. The scientific community has unraveled the utility of various editing tools from endonucleases to CRISPR/Cas in several aspects related to plant growth, development, and mitigation of stresses. The categorical focus on the development of tools and techniques including designing of binary vectors to facilitate ease in genome engineering are being pursued. Through this Review, we embark upon the conglomeration of various genome editing strategies that can be and are being used to design insect pest resistance in plants. Case studies and novel crop-based approaches that reiterate the successful use of these tools in insects as well as in plants are highlighted. Further, the Review also provides implications for the requirement of a specific regulatory framework and risk assessment of the edited crops. Genome editing toward insect pest management is here to stay, provided uncompromising efforts are made toward the identification of amiable target genes.

Comparison of outcomes between 2 week versus 4 week stenting in pediatric pyeloplasty-A single centre observational study.

OBJECTIVE: To compare the surgical outcomes, improvement in renal function and complications between early stent removal (2 weeks) and late stent removal (4 weeks) after pediatric open pyeloplasty. METHODS: A total of 72 open pyeloplasty were included in the study. Forty-three underwent late stent removal (Group 1) and 29 underwent early stent removal (Group 2). Pre-operative and post-operative follow-up data were compared to see the effect of early stent removal on the postoperative drainage pattern at 6 months after surgery and improvement in split function of affected kidney. The complications between the two groups were also compared. RESULTS: Both the groups were matched with respect to age, sex, side and antero-posterior diameter of pelvis. Pre-operative mean split function in Group 1 was 42% (26%-54%) while it was 39% (19%-42%) in Group 2 (p=0.37). Postoperative improvement in drainage pattern was seen in 69 out of 72 (96%) patients, 41 out of 43 (95%) in Group 1 and 28 out of 29 (97%) in Group 2. Improvement in split function occurred in 35 of 38 (97%) in Group 1 and 23 of 26 (88%) patients in Group 2 (p=0.51). Complications were seen in nine out of 72 (12.5%) patients. Incidence of complication in Group 1 was 16% (7/43) and Group 2 was 7% (2/29), and relative risk was 2.36. CONCLUSION: A shorter duration of double J stenting is as effective as a longer stenting period in terms of surgical success outcomes and improvement in split renal function along with a decreased risk of stent related complications.

Depression and dry eye disease: a need for an interdisciplinary approach?

A recent meta-analysis including data from 22 studies including 2.9 million patients found that anxiety and depression are more prevalent in patients with dry eye disease (DED) than in controls. DED is a common disorder of the tear film which can cause ocular irritation, foreign body sensation and visual disturbance. However there is often a great discrepancy between signs and symptoms of DED, which the symptoms often being more associated with non-ocular disorders such as depression and PTSD than to tear film parameters. In this way it could be considered as more of a psychiatric than ophthalmic complaint. DED and depression feedback on one another in a synergistic manner. Severity of DED is associated with symptoms of anxiety and depression. Treatment of DED could help reduce depression symptoms, but also effective management of depression could help alleviate symptoms of DED. Complicating this however is the evidence that SSRIs can exacerbate DED. This makes the management of these comorbidities more difficult, however there are putative therapeutic targets which may be a source of future treatments for DED-associated depression. In conclusion, it is clear that DED and depression are closely linked and influence one another in ways that drastically affect patients' lives. Collaboration between psychiatrists and ophthalmologists could be beneficial in the management of those with DED.

Silencing of HaAce1 gene by host-delivered artificial microRNA disrupts growth and development of Helicoverpa armigera.

The polyphagous insect-pest, Helicoverpa armigera, is a serious threat to a number of economically important crops. Chemical application and/or cultivation of Bt transgenic crops are the two strategies available now for insect-pest management. However, environmental pollution and long-term sustainability are major concerns against these two options. RNAi is now considered as a promising technology to complement Bt to tackle insect-pests menace. In this study, we report host-delivered silencing of HaAce1 gene, encoding the predominant isoform of H. armigera acetylcholinesterase, by an artificial microRNA, HaAce1-amiR1. Arabidopsis pre-miRNA164b was modified by replacing miR164b/miR164b* sequences with HaAce1-amiR1/HaAce1-amiR1* sequences. The recombinant HaAce1-preamiRNA1 was put under the control of CaMV 35S promoter and NOS terminator of plant binary vector pBI121, and the resultant vector cassette was used for tobacco transformation. Two transgenic tobacco lines expressing HaAce1-amiR1 was used for detached leaf insect feeding bioassays. Larval mortality of 25% and adult deformity of 20% were observed in transgenic treated insect group over that control tobacco treated insect group. The reduction in the steady-state level of HaAce1 mRNA was 70-80% in the defective adults compared to control. Our results demonstrate promise for host-delivered amiRNA-mediated silencing of HaAce1 gene for H. armigera management.

Bladder exstrophy-epispadias complex and the role of methylenetetrahydrofolate reductase C677T polymorphism: A case control study.

PURPOSE: The Bladder Exstrophy-Epispadias Complex (BEEC) is the most serious form of midline abdominal malformation. The etiology of BEEC is unknown and is thought to be multifactorial. Methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T is strongly associated with other midline abnormalities such as neural tube defects. No proper case-control study existed comparing MTHFR polymorphism with BEEC. We sought to find an association with MTHFR polymorphism and patients with bladder exstrophy (BE). MATERIALS AND METHODS: The design of the study was a case-control study, involving 50 children with BEEC and 50 normal healthy school children. Genetic analysis for MTHFR 677 polymorphism was carried out after DNA extraction and polymerase chain reaction amplification. Epidemiological analysis was done by using the birth defect questionnaire on parents of BEEC. RESULTS: Forty-two classical BE, two cloacal exstrophies (CE), four epispadias, and two exstrophy variant patients were a part of this study. Severe variety of BE had a significant association with C667T MTHFR polymorphism as compared to the normal control population (P = 0.01). CONCLUSION: C677T MTHFR polymorphism has a strong association with severe variety (CE) of BEEC occurrence.

Correlation between functional outcomes and postoperative pelvic magnetic resonance imaging in children with anorectal malformation.

BACKGROUND: Though the outcomes in operated children with anorectal malformation (ARM) have greatly improved, postoperative soiling and constipation remain major issues. Among the various factors described for poor outcomes; misplaced bowel, hypoplastic sphincters and obtuse anorectal angle bear special mention. The aim of this study was to compare the stooling outcomes, type of anomalies and surgical procedure with postoperative pelvic magnetic resonance imaging (MRI). MATERIALS AND METHODS: This was a cross-sectional study involving operated children of ARM who had at least 2 years of follow-up, and who were at least 3 years of age. The subtypes of ARM, surgical procedures, and functional outcomes were documented using the Krickenbeck classification. All children were subjected to a pelvic MRI. RESULTS: Thirty-three eligible children were part of this study. Twenty-two patients underwent posterior sagittal anorectoplasty, seven patients underwent abdominoperineal pull-through (APPT) and four patients underwent perineal operations. Local abnormalities were present in 66% patients, and 34% had abnormalities of the spine detected on MRI. Poorer stooling outcomes were twice as common in children with local pelvic MRI abnormalities as compared to asymptomatic children. The highest incidence of local abnormalities were seen in patients treated with APPT (P = 0.0001). No significant difference in the pelvic MRI was seen among children who were constipated and those who had soiling. CONCLUSION: MRI is a useful imaging modality in operated children of ARM with poor stooling outcomes. Local abnormalities were the most common in children undergoing abdominoperineal pull-through procedure.

Annular pancreas, type I choledochal cyst and malrotation in a low-birth weight newborn: A case report.

We present a low-birth weight newborn who presented with bilious vomit and had a "double bubble" sign on plain abdominal X-ray. Intraoperatively, we found annular pancreas with malrotation and type I choledochal cyst. To the best of our knowledge, this is the first reported case with a combination of these anomalies.