Browsing by Author "Ritu Raj"

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Assessment of solution stability and drug release properties of liposomal curcumin in peritoneal dialysis fluid and its synergistic antibacterial activity with vancomycin
(Elsevier B.V., 2022) Pranjali Pranjali; Ritu Raj; Khushboo Rani Singh; Narayan Prasad; Ranjan Kumar Singh; Krishna Mohan Poluri; Dinesh Kumar; Anupam Guleria
Infectious Peritonitis associated with recurrent and persistent infections is the major cause of technique failure of life-sustaining peritoneal dialysis (PD) therapy used for treating patients with end-stage renal failure (ESRF). The infections -if diagnosed timely- are usually resolved with empiric antibiotic treatment. However, the treatment of infections associated with drug resistant bacteria or fungal infections remains challenging, poses a very serious problem to the health of PD patients, and is the leading cause of mortality and morbidity. Therefore, the development of alternate approaches other than antibiotics are required to keep up with the constantly changing and increasing multiple drug resistance (MDR) of bacterial strains. Curcumin exhibits anti-oxidative/anti-inflammatory potential and remarkable wound healing properties. It also has broad-spectrum anti-bacterial/anti-biofilm effects and its synergistic antibacterial activity with several antibiotics (including those used clinically for the treatment of PD associated infections) is well proven against variety of pathogenic infections including MDR strains. However, poor water-solubility of curcumin (<0.125 mg/L) remains a major barrier to achieve desirable bioavailability and further limit its therapeutic efficacy. Among the various drug carrier strategies, liposomal encapsulation has been found to be most promising mode to remarkably enhance the therapeutic index of curcumin by facilitating its gastric absorption, protecting its enzymatic degradation and allowing its slow release over time for maximum benefits. However, to date, the potential of liposomal curcumin has not been explored for the treatment of PD associated infections. Starting our efforts in this direction, a comprehensive assessment of solution stability and drug release properties of curcumin-loaded liposomal vesicles has been demonstrated in peritoneal dialysis fluid. The results clearly indicated an excellent solution stability of curcumin loaded inside liposome and the formulation affirms the regulated curcumin release enhancing the bioavailability. Further, we evaluated the synergistic antibacterial efficacy of curcumin-loaded liposomal formulation with vancomycin against the Staphylococcus aureus and Escherichia coli – pathogens (known for causing intra-peritoneal infections during PD). This synergy strategy resulted in outstanding improvement in bacterial inhibition efficacy of liposomal curcumin at significantly lowered doses. The results of the present study propose lipocurcumin as a potent antibiotic additive to vancomycin to cure PD-infections caused by antibiotic-resistant bacteria. © 2022
Association of altered metabolic profiles and long non-coding RNAs expression with disease severity in breast cancer patients: analysis by 1H NMR spectroscopy and RT-q-PCR
(Springer, 2023) Anusmita Shekher; Puneet; Nikee Awasthee; Umesh Kumar; Ritu Raj; Dinesh Kumar; Subash Chandra Gupta
Introduction: Globally, one of the major causes of cancer related deaths in women is breast cancer. Although metabolic pattern is altered in cancer patients, robust metabolic biomarkers with a potential to improve the screening and disease monitoring are lacking. A complete metabolome profiling of breast cancer patients may lead to the identification of diagnostic/prognostic markers and potential targets. Objectives: The aim of this study was to analyze the metabolic profile in the serum from 43 breast cancer patients and 13 healthy individuals. Materials & methods: We used 1H NMR spectroscopy for the identification and quantification of metabolites. q-RT-PCR was used to examine the relative expression of lncRNAs. Results: Metabolites such as amino acids, lipids, membrane metabolites, lipoproteins, and energy metabolites were observed in the serum from both patients and healthy individuals. Using unsupervised PCA, supervised PLS-DA, supervised OPLS-DA, and random forest classification, we observed that more than 25 metabolites were altered in the breast cancer patients. Metabolites with AUC value > 0.9 were selected for further analysis that revealed significant elevation of lactate, LPR and glycerol, while the level of glucose, succinate, and isobutyrate was reduced in breast cancer patients in comparison to healthy control. The level of these metabolites (except LPR) was altered in advanced-stage breast cancer patients in comparison to early-stage breast cancer patients. The altered metabolites were also associated with over 25 signaling pathways related to metabolism. Further, lncRNAs such as H19, MEG3 and GAS5 were dysregulated in the breast tumor tissue in comparison to normal adjacent tissue. Conclusion: The study provides insights into metabolic alteration in breast cancer patients. It also provides an avenue to examine the association of lncRNAs with metabolic patterns in patients. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Elevated Circulatory Proline to Glutamine Ratio (PQR) in Endometriosis and Its Potential as a Diagnostic Biomarker
(American Chemical Society, 2022) Kusum Kusum; Ritu Raj; Sangeeta Rai; Pranjali Pranjali; Ashish Ashish; Sara Vicente-Muñoz; Radha Chaube; Dinesh Kumar
Endometriosis (EM) is a hormone-dependent gynecological disease associated with chronic pelvic pain and altered immuno-inflammatory processes. It shares some cancer-like characteristics such as increased proline biosynthesis and activated glutaminolysis. Both proline and glutamine are interconvertible metabolically, and studies have shown their roles in cancer cell metabolic reprogramming, redox homeostasis, occurrence/development of endometrial carcinoma, and its further progression toward the malignant state. So based on this, we hypothesized that the circulatory proline to glutamine ratio (PQR) would be altered in EM and may serve as an indicative biomarker to improve the clinical diagnosis of EM. In present study, the circulatory-PQR levels were estimated for 39 EM patients and 48 age matched healthy female subjects using 800 MHz NMR spectroscopy. Among 39 EM patients, 15 were in the clinical stages I to II and referred to here as moderate EM (MEM) patients and 24 were in the clinical stages III to IV and referred here as severe EM (SEM) patients. The circulatory-PQR levels were significantly increased in EM patients (0.99 ± 0.13 μM in MEM; 1.39 ± 0.22 μM in SEM) compared to normal control (NC) subjects (0.52 ± 0.05 μM in NC). Further, the circulatory PQR levels exhibit the highest diagnostic potential with area under receiver operating characteristic (AUROC) curve values equal to 0.87 ± 0.04 [95%CI = 0.79-0.96] for MEM and 0.89 ± 0.04 [95% CI = 0.82-0.96] for SEM. These results suggested that circulatory-PQR has significant potential to serve as a noninvasive biomarker for diagnostic/prognostic screening of EM and further underscored the importance of these two nonessential amino acids (proline and glutamine) in cancer metabolism. © 2022 American Chemical Society.
In vitro and ex vivo relaxometric properties of ethylene glycol coated gadolinium oxide nanoparticles for potential use as contrast agents in magnetic resonance imaging
(American Institute of Physics Inc., 2020) Anamika Chaturvedi; Pranjali Pranjali; Mukesh Kumar Meher; Ritu Raj; Madhuri Basak; Ranjan Kumar Singh; Krishna Mohan Poluri; Dinesh Kumar; Anupam Guleria
Magnetic nanoparticles (MNPs) have widely demonstrated their applicability in many biomedical applications including magnetic resonance imaging (MRI), hyperthermia, and drug delivery. However, the effectiveness of MNPs can be limited for in vivo applications due to their hydrophobic surfaces leading to nanoparticle agglomeration and thus requires appropriate surface modification to enhance colloidal stability. Glycols are widely used coating material for surface modifications of MNPs to improve their physicochemical properties and biocompatibility. The present work reports the preparation of two different sized ethylene glycol coated gadolinium oxide nanoparticles (EG@Gd2O3 NPs) using two different synthesis approaches and their applicability as contrast agents in MRI. Thermo-gravimetric analysis and Fourier transform infrared spectroscopy confirmed the successful coating of ethylene glycol on the surface of NPs. We found that independent of the size of NPs, the globular shaped EG@Gd2O3 NPs exhibited similar crystal structures, magnetic properties, and cellular cytotoxicity behavior. However, a significant impact of size on MRI contrast enhancement properties was seen. It was revealed that the relaxivity of EG@Gd2O3 NPs increases with a decrease in particle size. Small sized EG@Gd2O3 NPs (∼12 nm) exhibited a high specific in vitro and ex vivo longitudinal relaxivity of 3.7 and 1.5 mM-1 s-1, respectively, thus clearly elucidating the potential of these NPs for use as local contrast enhancement agents. The present study gives insights into the intrinsic dependence of magnetic resonance contrast effects of NPs on particle size and surface coating layer mass ratio and thus demonstrates the development of efficient magnetic nanoparticles based contrast agents by fine tuning of particle size and surface properties. © 2020 Author(s).
Integration of transcriptomics and metabolomics data revealed role of insulin resistant SNW1 gene in the pathophysiology of gestational diabetes
(Nature Research, 2025) Ravi Bhushan; Rimjhim Trivedi; Ritu Raj; Anjali Rani; Sangeeta Rai; Anima Tripathi; Shiv Govind Rawat; Ajay Kumar; Dinesh Kumar; Pawan Kumar Dubey
Gestational Diabetes Mellitus (GDM) is an emerging maternal health problem with increasing incidences. The lack of complete understanding of its pathophysiological mechanisms and novel regulatory biomarkers makes early diagnosis difficult. High-throughput RNA sequencing and computational bioinformatics analyses were conducted to identify novel hub genes, and their regulatory mechanisms were validated through qRT-PCR, western blot, and siRNA-mediated knockdown studies. Intermediate metabolites and circulatory levels of amino acids in the serum of GDM patients and healthy controls were measured. Transcriptomic studies identified SNW1 as the most sensitive and specific biomarker, significantly up-regulated in GDM (fold change = 1.09; p < 0.001). Metabolomic studies indicated significantly elevated gluconeogenesis in GDM, evidenced by decreased levels of alanine and increased levels of pyruvate and glucose compared to controls. siRNA-mediated knockdown of SNW1 in PANC1 cells resulted in significant down-regulation of alanine aminotransferase (ALT/GPT) and insulin receptor substrate (IRS1), while glucose transporters (GLUT2/GLUT4) and insulin (INS) were significantly up-regulated at both mRNA and protein levels. This study identified SNW1 as a novel insulin-resistant gene that induces hyperglycemia by elevating gluconeogenesis and decreasing glucose uptake. SNW1 may be considered a potential therapeutic target with clinical utility for the management of GDM. © The Author(s) 2025.
Investigation of magnetic resonance contrast properties of PEG-coated gadolinium oxide nanoparticles in various biological environments
(Institute of Physics, 2024) Anamika Chaturvedi; Pranjali Pranjali; Ritu Raj; Ayush Shukla; Ranjana Singh; Deepak Kumar Tripathi; Krishna Mohan Poluri; Ranjan Kumar Singh; Dinesh Kumar; Anupam Guleria
Magnetic nanoparticles (MNPs) are promising tools for biomedical applications, particularly in molecular imaging using magnetic resonance imaging (MRI). The unique magnetic properties of MNPs, combined with their similarity in size to biological objects, make them ideal candidates for in situ imaging probes. The present study explores the use of magnetic nanoparticles (MNPs) as contrast agents in magnetic resonance imaging (MRI) for improved diagnostic accuracy. Specifically, the study investigates the MR contrast properties of polyethylene glycol-coated gadolinium oxide nanoparticles (PEG@GONPs) in five different biological fluids. The nanoparticles were synthesized using the polyol route and their size, shape, and morphology were characterized using TEM, SEM, and FT-IR spectroscopy. The magnetic resonance (MR) relaxivity of PEG@GONPs was studied in different biologically relevant media, and results revealed highest relaxivity in plasma as compared to other media. In addition, comparative analysis of proton relaxivity of the synthesized nanoparticles was carried out with a well-known gadolinium-based contrast agent, Omniscan, in various medium. The present findings revealed that PEG@GONPs can serve as an effective contrast agent for MRI imaging in biological fluids such as plasma, which is crucial for preclinical diagnosis of specific diseases and lesions. The high relaxivity observed in plasma could be attributed to the interaction of the nanoparticles with plasma proteins, amplifying their magnetic properties which further improve their ability to produce contrast in MR images. © 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.