An In Silico Drug Repositioning Strategy to Identify Specific STAT-3 Inhibitors for Breast Cancer

Sruthy Sathish 조선대학교 기초과학연구원 2023 조선자연과학논문집 Vol.16 No.4

Breast cancer continues to pose a substantial worldwide health challenge, thereby requiring the development of innovative strategies to discover new therapeutic interventions. Signal Transducer and Activator of Transcription 3 (STAT-3) has been identified as a significant factor in the development of several types of cancer, including breast cancer. This is primarily attributed to its diverse functions in promoting tumour formation and conferring resistance to therapeutic interventions. This study presents an in silico drug repositioning approach that focuses on identifying specific inhibitors of STAT-3 for the purpose of treating breast cancer. We initially examined the structural and functional attributes of STAT-3, thereby elucidating its crucial involvement in cellular signalling cascades. A comprehensive virtual screening was performed on a diverse collection of drugs that have been approved by the FDA from zinc15 database. Various computational techniques, including molecular docking, cross docking, and cDFT analysis, were utilised in order to prioritise potential candidates. This prioritisation was based on their predicted binding energies and outer molecular orbital reactivity. The findings of our study have unveiled a Dihydroergotamine and Paritaprevir that have been approved by the FDA and exhibit considerable promise as selective inhibitors of STAT-3. In conclusion, the utilisation of our in silico drug repositioning approach presents a prompt and economically efficient method for the identification of potential compounds that warrant subsequent experimental validation as selective STAT-3 inhibitors in the context of breast cancer. The present study highlights the considerable potential of employing computational strategies to expedite the drug discovery process. Moreover, it provides valuable insights into novel avenues for targeted therapeutic interventions in the context of breast cancer treatment.

Phytocompounds from T. conoides identified for targeting JNK2 protein in breast cancer

Sruthy Sathish,Thirumurthy Madhavan 조선대학교 기초과학연구원 2022 조선자연과학논문집 Vol.15 No.4

The Modified Eulerian-Lagrangian Formulation for Cauchy Boundary Condition Under Dispersion Dominated Flow Regimes: A Novel Numerical Approach and its Implication on Radioactive Nuclide Migration or Solute Transport in the Subsurface Environment

Sruthi, K.V.,Suk, Heejun,Lakshmanan, Elango,Chae, Byung-Gon,Kim, Hyun-su Korean Society of Soil and Groundwater Environment 2015 지하수토양환경 Vol.20 No.2

The present study introduces a novel numerical approach for solving dispersion dominated problems with Cauchy boundary condition in an Eulerian-Lagrangian scheme. The study reveals the incapability of traditional Neuman approach to address the dispersion dominated problems with Cauchy boundary condition, even though it can produce reliable solution in the advection dominated regime. Also, the proposed numerical approach is applied to a real field problem of radioactive contaminant migration from radioactive waste repository which is a major current waste management issue. The performance of the proposed numerical approach is evaluated by comparing the results with numerical solutions of traditional FDM (Finite Difference Method), Neuman approach, and the analytical solution. The results show that the proposed numerical approach yields better and reliable solution for dispersion dominated regime, specifically for Peclet Numbers of less than 0.1. The proposed numerical approach is validated by applying to a real field problem of radioactive contaminant migration from radioactive waste repository of varying Peclet Number from 0.003 to 34.5. The numerical results of Neuman approach overestimates the concentration value with an order of 100 than the proposed approach during the assessment of radioactive contaminant transport from nuclear waste repository. The overestimation of concentration value could be due to the assumption that dispersion is negligible. Also our application problem confirms the existence of real field situation with advection dominated condition and dispersion dominated condition simultaneously as well as the significance or advantage of the proposed approach in the real field problem.

The Modified Eulerian-Lagrangian Formulation for Cauchy Boundary Condition Under Dispersion Dominated Flow Regimes: A Novel Numerical Approach and its Implication on Radioactive Nuclide Migration or Solute Transport in the Subsurface Environment

K.V. Sruthi,석희정,Elango Lakshmanan,채병곤,김현수 한국지하수토양환경학회 2015 지하수토양환경 Vol.20 No.2

The present study introduces a novel numerical approach for solving dispersion dominated problems with Cauchy boundary condition in an Eulerian-Lagrangian scheme. The study reveals the incapability of traditional Neuman approach to address the dispersion dominated problems with Cauchy boundary condition, even though it can produce reliable solution in the advection dominated regime. Also, the proposed numerical approach is applied to a real field problem of radioactive contaminant migration from radioactive waste repository which is a major current waste management issue. The performance of the proposed numerical approach is evaluated by comparing the results with numerical solutions of traditional FDM (Finite Difference Method), Neuman approach, and the analytical solution. The results show that the proposed numerical approach yields better and reliable solution for dispersion dominated regime, specifically for Peclet Numbers of less than 0.1. The proposed numerical approach is validated by applying to a real field problem of radioactive contaminant migration from radioactive waste repository of varying Peclet Number from 0.003 to 34.5. The numerical results of Neuman approach overestimates the concentration value with an order of 100 than the proposed approach during the assessment of radioactive contaminant transport from nuclear waste repository. The overestimation of concentration value could be due to the assumption that dispersion is negligible. Also our application problem confirms the existence of real field situation with advection dominated condition and dispersion dominated condition simultaneously as well as the significance or advantage of the proposed approach in the real field problem.

Validation of Combs prognostic scoring system in Indian recurrent glioma patients treated with re-radiation

Debnarayan Dutta(Debnarayan Dutta ),Meenu Jose(Meenu Jose ),Sruthi Kalavagunta(Sruthi Kalavagunta ),Ajay Sasidharan(Ajay Sasidharan ),Haridas Nair(Haridas Nair ),Annex H. Edappattu(Annex H. Edappattu 대한방사선종양학회 2024 Radiation Oncology Journal Vol.42 No.1

Purpose: Retrospective audit of recurrent glioma patients treated by different fractionation schedules and to validate the modified Combs prognostic score in Indian patient cohort. Materials and Methods: Between Jan 2009 and June 2022, 66 recurrent gliomas patients treated with standard adjuvant treatment—radiation (RT) ± temozolomide (chemotherapy)—and re-treated with RT (± chemotherapy) were categorized as per modified Combs prognostic criteria and outcomes were compared. Results: Sixty-six patients with recurrent gliomas who received reirradiation (re-RT) were audited—53% males; 61% Karnofsky performance status (KPS) ≥80 at time of re-RT; median age 41.5 years (range, 6 to 70 years); 67% <50 years; primary histology low-grade glioma in 33% ; grade III 27%, grade IV 40%; initial median dose of 60 Gy equivalent dose in 2 Gy fractions (EQD2); maximum safe resection at recurrence 41%; mean and median follow-up 78 ± 51 months and 66 months. Mean time interval between RT was 46.4 ± 39 months. Mean planning target volume (PTV) volume in conventional RT (Conv-RT), hypofractionated RT (Hypo-RT), and ultra-hypofractionated RT (UF-RT) was 226.1 ± 140.7 mL, 162.8 ± 123.3 mL, and 143.3 ± 145.8 mL. Mean dose for Conv-RT, Hypo-RT, and UF-RT was 50 Gy (range, 40 to 60), 31 Gy (range, 20 to 40), and 20 Gy (range, 10 to 30). Mean overall survival (OS) in Conv-RT, Hypo-RT, and UF-RT cohort was 18.8 months (range, 2.4 to 76.8); 6.6 months (range, 2 to 17.4), and 13.9 months (range, 3 to 131.9). Median OS as per Combs criteria were 16.6 months (Group a), 24.6 months (Group b), 4.6 months (Group c), and 3 months (Group d). Significant survival benefit was with good KPS score (KPS >80 vs. <80; 20.46 vs. 5.25 months; p < 0.001), patients receiving salvage chemotherapy (20.46 vs. 6.96 months; p = 0.001), and patients received re-RT biological equivalent dose (BED3) >80 Gy (16.62 vs. 5.48 months; p = 0.03). Median overall survival (OS) in our patient cohort and Combs cohort in Group a was 16.6 and 19.5 months; Group b was 24.6 and 11.3 months; Group c was 4.7 and 8.1 months, and Group d was 2 and 5.5 months, respectively. Six months survival in our patient cohort and Combs cohort in Groups a, b, c, d were 100%, 92%, 34%, 17% and 94%, 79%, 70%, 41%, respectively. Twelve months survival in our patient cohort and Combs cohort in Groups a, b, c, d were 88%, 74%, 22%, 0% and 88%, 47%, 22%, 7%, respectively. Conclusion: Modified Combs prognostic factors predicts OS and is applicable in Indian subcontinent patient population.

P2X Receptor 3D Structure Prediction Using Homology Modelling

Thirumurthy Madhavan,Sruthy Sathish 조선대학교 기초과학연구원 2023 조선자연과학논문집 Vol.16 No.1

Assessing the Systemic Toxicity in Rabbits after Sub Acute Exposure to Ocular Irritant Chemicals

Cherian Sebastian Reshma,Sudhakaran Sruthi,Santhakumar Syama,Vishwanath Gayathri,Parayanthala Valappil Mohanan 한국독성학회 2015 Toxicological Research Vol.31 No.1

Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers (IL-1α, IL-1β, IL-8 and TNF-α) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.

Two‐dimensional Ti 3 C 2 MXene for photocatalytic hydrogen production: A

Reghunath B. Shalini,Rajasekaran Sruthi,Mathew Sandra,Pinheiro Dephan,Devi K. R Sunaja,정시언,Jayaraman Theerthagiri,최명룡 대한화학회 2023 Bulletin of the Korean Chemical Society Vol.44 No.12

This study focuses on the utilization of two‐dimensional Ti 3 C 2 MXene as a catalyst for photocatalytic hydrogen production. MXenes, a class of transition metal carbides/nitrides, exhibit exceptional properties conducive to enhancing photocatalytic reactions. This research explores the performance of Ti 3 C 2 MXene as a cocatalyst in photocatalytic systems, aiming to improve charge separation, inhibit recombination, and facilitate efficient hydrogen evolution from water under light irradiation. The synthesis methods, catalyst‐loading strategies, and overall photocatalytic mechanisms are investigated, shedding light on the potential of Ti 3 C 2 MXene as a promising material for advancing hydrogen production through sustainable means. This study focuses on the utilization of two-dimensional Ti3C2 MXene as a catalyst for photocatalytic hydrogen production. MXenes, a class of transition metal carbides/nitrides, exhibit exceptional properties conducive to enhancing photocatalytic reactions. This research explores the performance of Ti3C2 MXene as a cocatalyst in photocatalytic systems, aiming to improve charge separation, inhibit recombination, and facilitate efficient hydrogen evolution from water under light irradiation. The synthesis methods, catalyst-loading strategies, and overall photocatalytic mechanisms are investigated, shedding light on the potential of Ti3C2 MXene as a promising material for advancing hydrogen production through sustainable means.

강변여과수 지역에서 열추적자 기법을 이용한 주변 지하수 속도 분포 추정

강혜진 ( Kang Hyejin ),( Sruthi Kv ),석희준 ( Heejun Suk ),고동찬 ( Dong Chan Koh ) 대한지질공학회 2014 대한지질공학회 학술발표회논문집 Vol.2014 No.1

Assessing the Systemic Toxicity in Rabbits after Sub Acute Exposure to Ocular Irritant Chemicals

Reshma, Cherian Sebastian,Sruthi, Sudhakaran,Syama, Santhakumar,Gayathri, Vishwanath,Mohanan, Parayanthala Valappil Korean Society of ToxicologyKorea Environmental Mu 2015 Toxicological Research Vol.31 No.1

Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers ($IL-1{\alpha}$, $IL-1{\beta}$, IL-8 and $TNF-{\alpha}$) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.