Uncertainty estimation and evaluation of deformation image registration based convolutional neural networks.

Objective.Fast and accurate deformable image registration (DIR), including DIR uncertainty estimation, is essential for safe and reliable clinical deployment. While recent deep learning models have shown promise in predicting DIR with its uncertainty, challenges persist in proper uncertainty evaluation and hyperparameter optimization for these methods. This work aims to develop and evaluate a model that can perform fast DIR and predict its uncertainty in seconds.Approach.This study introduces a novel probabilistic multi-resolution image registration model utilizing convolutional neural networks to estimate a multivariate normal distributed dense displacement field (DDF) in a multimodal image registration problem. To assess the quality of the DDF distribution predicted by the model, we propose a new metric based on the Kullback-Leibler divergence. The performance of our approach was evaluated against three other DIR algorithms (VoxelMorph, Monte Carlo dropout, and Monte Carlo B-spline) capable of predicting uncertainty. The evaluation of the models included not only the quality of the deformation but also the reliability of the estimated uncertainty. Our application investigated the registration of a treatment planning computed tomography (CT) to follow-up cone beam CT for daily adaptive radiotherapy.Main results.The hyperparameter tuning of the models showed a trade-off between the estimated uncertainty's reliability and the deformation's accuracy. In the optimal trade-off, our model excelled in contour propagation and uncertainty estimation (p <0.05) compared to existing uncertainty estimation models. We obtained an average dice similarity coefficient of 0.89 and a KL-divergence of 0.15.Significance.By addressing challenges in DIR uncertainty estimation and evaluation, our work showed that both the DIR and its uncertainty can be reliably predicted, paving the way for safe deployment in a clinical environment.

Neuroglia targeting nano-therapeutic approaches to rescue aging and neurodegenerating brain.

Despite intense efforts at the bench, the development of successful brain-targeting therapeutics to relieve malicious neural diseases remains primitive. The brain, being a beautifully intricate organ, consists of heterogeneous arrays of neuronal and glial cells. Primarily acting as the support system for neuronal functioning and maturation, glial cells have been observed to be engaged more apparently in the progression and worsening of various neural pathologies. The diseased state is often related to metabolic alterations in glial cells, thereby modulating their physiological homeostasis in conjunction with neuronal dysfunction. A plethora of data indicates the effect of oxidative stress, protein aggregation, and DNA damage in neuroglia impairments. Still, a deeper insight is needed to gain a conflict-free understanding in this arena. As a consequence, glial cells hold the potential to be identified as promising targets for novel therapeutic approaches aimed at brain protection. In this review, we describe the recent strides taken in the direction of understanding the impact of oxidative stress, protein aggregation, and DNA damage on neuroglia impairment and neuroglia-directed nanotherapeutic approaches to mitigate the burden of various neural disorders.

Oncogenic ETS fusions promote DNA damage and proinflammatory responses via pericentromeric RNAs in extracellular vesicles.

Aberrant expression of the E26 transformation-specific (ETS) transcription factors characterizes numerous human malignancies. Many of these proteins, including EWS:FLI1 and EWS:ERG fusions in Ewing sarcoma (EwS) and TMPRSS2:ERG in prostate cancer (PCa), drive oncogenic programs via binding to GGAA repeats. We report here that both EWS:FLI1 and ERG bind and transcriptionally activate GGAA-rich pericentromeric heterochromatin. The respective pathogen-like HSAT2 and HSAT3 RNAs, together with LINE, SINE, ERV, and other repeat transcripts, are expressed in EwS and PCa tumors, secreted in extracellular vesicles (EVs), and are highly elevated in plasma of patients with EwS with metastatic disease. High human satellite 2 and 3 (HSAT2,3) levels in EWS:FLI1- or ERG-expressing cells and tumors were associated with induction of G2/M checkpoint, mitotic spindle, and DNA damage programs. These programs were also activated in EwS EV-treated fibroblasts, coincident with accumulation of HSAT2,3 RNAs, proinflammatory responses, mitotic defects, and senescence. Mechanistically, HSAT2,3-enriched cancer EVs induced cGAS-TBK1 innate immune signaling and formation of cytosolic granules positive for double-strand RNAs, RNA-DNA, and cGAS. Hence, aberrantly expressed ETS proteins derepress pericentromeric heterochromatin, yielding pathogenic RNAs that transmit genotoxic stress and inflammation to local and distant sites. Monitoring HSAT2,3 plasma levels and preventing their dissemination may thus improve therapeutic strategies and blood-based diagnostics.

Futuristic Alzheimer's therapy: acoustic-stimulated piezoelectric nanospheres for amyloid reduction.

The degeneration of neurons due to the accumulation of misfolded amyloid aggregates in the central nervous system (CNS) is a fundamental neuropathology of Alzheimer's disease (AD). It is believed that dislodging/clearing these amyloid aggregates from the neuronal tissues could lead to a potential cure for AD. In the present work, we explored biocompatible polydopamine-coated piezoelectric polyvinylidene fluoride (DPVDF) nanospheres as acoustic stimulus-triggered anti-fibrillating and anti-amyloid agents. The nanospheres were tested against two model amyloidogenic peptides, including the reductionist model-based amyloidogenic dipeptide, diphenylalanine, and the amyloid polypeptide, amyloid beta (Aß42). Our results revealed that DPVDF nanospheres could effectively disassemble the model peptide-derived amyloid fibrils under suitable acoustic stimulation. In vitro studies also showed that the stimulus activated DPVDF nanospheres could efficiently alleviate the neurotoxicity of FF fibrils as exemplified in neuroblastoma, SHSY5Y, cells. Studies carried out in animal models further validated that the nanospheres could dislodge amyloid aggregates in vivo and also help the animals regain their cognitive behavior. Thus, these acoustic stimuli-activated nanospheres could serve as a novel class of disease-modifying nanomaterials for non-invasive electro-chemotherapy of Alzheimer's disease.

Animal models for induction of diabetes and its complications.

Objectives: Animal models are widely used to develop newer drugs for treatment of diabetes and its complications. We conducted a systematic review to find various animal models to induce diabetes and also the suitable methods in various diabetic complications. With an emphasis on the animal models of diabetes induction, this review provides a basic overview of diabetes and its various types. It focused on the use of rats and mice for chemical, spontaneous, surgical, genetic, viral, and hormonal induction approaches. Methods: All observations and research conducted on Diabetes and its complications published up to 18 May 2023 in PubMed, Web of Science, Scopus and Conchrane Library databases were included. Main outcome measures were reporting the induction of diabetes in experimental animals, the various animal models for diabetic complications including diabetic nephropathy, diabetic retinopathy, diabetic neuropathy and diabetic osteopathy. The quality of reporting of included articles and risk of bias were assessed. Results: We reached various articles and found that rats and mice are the most frequently used animals for inducing diabetes. Chemical induction is the most commonly used followed by spontaneous and surgical methods. With slight modification various breeds and species are developed to study and induce specific complications on eyes, kidneys, neurons and bones. Conclusions: Our review suggested that rats and mice are the most suitable animals. Furthermore, chemical induction is the method frequently used by experimenters. Moreover, high quality studies are required to find the suitable methods for diabetic complications.

Carbon dioxide sequestration in natural gas hydrates - effect of flue and noble gases.

Clean energy is one of the immediate requirements all over the world to tackle the global energy demands. Natural gas hydrates (NGHs) are one of the proposed alternatives that could be used to extract methane as clean energy and simultaneously sequestrate carbon dioxide. However, the formation of CH4-CO2 mixed hydrates and the first hydrate layer besides the interface reduces the rate of CO2 sequestration and methane extraction in NGHs, and thus, multistep extraction of methane is one of the proposed solutions. We report the atomic level factors that could enhance CO2 sequestration in the newly formed first hydrate layer besides the interface in the presence of flue and noble gases using DFT calculations and molecular dynamics simulations at 250 K and 0.15 kbar. The simulations show the formation of stable dual cages (large-large or small-large) that lead to the formation of a four-caged, Y-shaped cluster (growth synthon) which leads to the formation of a hydrate unit cell in heterogeneous medium. Among the flue and noble gases, only argon forms energetically favorable dual cages with itself and CO2 due to which enhanced CO2 sequestration is observed at different concentrations of Ar and CO2 where the CO2 : Ar (2.5 : 1.5) system shows the best CO2 sequestration in the first layer besides the interface. The results also provide understanding into the previously reported concentration dependent CO2 selectivity in sI hydrates in the presence of third gases (N2 and H2S).

Rapid purification and multiparametric characterization of circulating small extracellular vesicles utilizing a label-free lab-on-a-chip device.

Nano-scale extracellular vesicles are lipid-bilayer delimited particles that are naturally secreted by all cells and have emerged as valuable biomarkers for a wide range of diseases. Efficient isolation of small extracellular vesicles while maintaining yield and purity is crucial to harvest their potential in diagnostic, prognostic, and therapeutic applications. Most conventional methods of isolation suffer from significant shortcomings, including low purity or yield, long duration, need for large sample volumes, specialized equipment, trained personnel, and high costs. To address some of these challenges, our group has reported a novel insulator-based dielectrophoretic device for rapid isolation of small extracellular vesicles from biofluids and cell culture media based on their size and dielectric properties. In this study, we report a comprehensive characterization of small extracellular vesicles isolated from cancer-patients' biofluids at a twofold enrichment using the device. The three-fold characterization that was performed using conventional flow cytometry, advanced imaging flow cytometry, and microRNA sequencing indicated high yield and purity of the isolated small extracellular vesicles. The device thus offers an efficient platform for rapid isolation while maintaining biomolecular integrity.

Occluded Coronary Artery among Non-ST Elevation Myocardial Infarction Patients in Department of Cardiology of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Non-ST elevation myocardial infarction is frequently thought to be caused by incomplete blockage of the culprit artery, whereas ST elevation myocardial infarction is frequently thought to be caused by total occlusion of the culprit artery. The objective of the study was to find out the prevalence of occluded coronary arteries among non-ST elevation myocardial infarction patients department of cardiology of a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among non-ST elevation myocardial infarction patients in a tertiary care centre from 22 June 2020 to 21 June 2021 after taking ethical approval from the Institutional Review Committee [Reference number: 4271 (6-11) E2 076/077]. A total of 196 patients were included in the study by simple randomized sampling. Data on the patient's clinical profile, angiographic findings, and in-hospital complications were recorded. Point estimate and 95% Confidence Interval were calculated. Results: Among 126 non-ST elevation myocardial infarction patients included in the study, the prevalence of occluded coronary artery was 41 (32.54%) (24.36-40.72, 95% Confidence Interval). Conclusions: The prevalence of occluded coronary arteries was similar to the studies done in similar settings. Keywords: coronary angiography; MINOCA; Non-ST elevation myocardial infarction.

Dosimetric characterization of single- and dual-port temporary tissue expanders for postmastectomy radiotherapy using Monte Carlo methods.

Purpose: The aim of this work was two-fold: a) to assess two treatment planning strategies for accounting CT artifacts introduced by temporary tissue-expanders (TTEs); b) to evaluate the dosimetric impact of two commercially available and one novel TTE. Methods: The CT artifacts were managed using two strategies. 1) Identifying the metal in the RayStation treatment planning software (TPS) using image window-level adjustments, delineate a contour enclosing the artifact, and setting the density of the surrounding voxels to unity (RS1). 2) Registering a geometry template with dimensions and materials from the TTEs (RS2). Both strategies were compared for DermaSpan, AlloX2, and AlloX2-Pro TTEs using Collapsed Cone Convolution (CCC) in RayStation TPS, Monte Carlo simulations (MC) using TOPAS, and film measurements. Wax slab phantoms with metallic ports and breast phantoms with TTEs balloons were made and irradiated with a 6 MV AP beam and partial arc, respectively. Dose values along the AP direction calculated with CCC (RS2) and TOPAS (RS1 and RS2) were compared with film measurements. The impact in dose distributions was evaluated with RS2 by comparing TOPAS simulations with and without the metal port. Results: For the wax slab phantoms, the dose differences between RS1 and RS2 were 0.5% for DermaSpan and AlloX2 but 3% for AlloX2-Pro. From TOPAS simulations of RS2, the impact in dose distributions caused by the magnet attenuation was (6.4 ± 0.4) %, (4.9 ± 0.7)%, and (2.0 ± 0.9)% for DermaSpan, AlloX2, and AlloX2-Pro, respectively. With breast phantoms, maximum differences in DVH parameters between RS1 and RS2 were as follows. For AlloX2 at the posterior region: (2.1 ± 1.0)%, (1.9 ± 1.0)% and (1.4 ± 1.0)% for D1, D10, and average dose, respectively. For AlloX2-Pro at the anterior region (-1.0 ± 1.0)%, (-0.6 ± 1.0)% and (-0.6 ± 1.0)% for D1, D10 and average dose, respectively. The impact in D10 caused by the magnet was at most (5.5 ± 1.0)% and (-0.8 ± 1.0)% for AlloX2 and AlloX2-Pro, respectively. Conclusion: Two strategies for accounting for CT artifacts from three breast TTEs were assessed using CCC, MC, and film measurements. This study showed that the highest differences with respect to measurements occurred with RS1 and can be mitigated if a template with the actual port geometry and materials is used.

Potential therapeutic effect of Carica papaya leaves extract on immune response, biochemical and hematological mechanisms on cecal ligation and puncture model of sepsis in rats: an in vivo study.

Antibiotics and immunotherapies possess unavoidable adverse effects that hinder sepsis management. Herbal drugs have demonstrated potential immunomodulatory properties vital for sepsis treatment. We hypothesized in the present study that the use of Carica papaya leaves extract had the potential to improve survival and modulate immune cytokine release during sepsis. Animals were subjected to cecal ligation and puncture (CLP) to induce sepsis. Septic rats divided into 10 groups received ethanol extract of C. papaya leaves (50 and 100 mg/kg), imipenem (120 mg/kg) and cyclophosphamide (CP, 10 mg/kg). To investigate the immunomodulatory potentials of EE, cytokine levels like interleukin (IL-6), tumor necrosis factor (TNF-α), and IL-10 along with hematological and biochemical parameters were analyzed. Our results exhibited improved survival rates concerning ethanol extract treatment alone and in combination with imipenem and CP (100%) as compared to the CLP group (33.3%) on day 7 post-surgery. The combination treatment of ethanol extract with imipenem and CP significantly (P < 0.001) ameliorated cytokine levels and hematological and biochemical parameters in septic rats. A histopathological examination suggested improved liver and kidney tissue condition after combination treatment as compared to the CLP group. Therefore, it was concluded that combination therapy of extract with imipenem and CP improved survival rates and marked immunomodulatory potential in septic rats compared to monotherapy. The findings suggested the use of a mixture of these drugs in clinical settings to treat sepsis.

A Rare Coexistence of Simultaneous Cardio-Cerebral Infarction.

Background: Contemporaneous acute myocardial infarction (AMI) and acute ischemic stroke (AIS), termed cardio-cerebral infarction (CCI), is a rare medical emergency. The effectual management of this situation is exigent since early management of one condition will inevitably delay the other. Case Presentation. A 60-year-old woman presented to our hospital with concurrent AMI of the inferior left ventricular wall, complicated by cardiogenic shock and transient complete heart block, and AIS of more than 4.5 hour duration. The cerebral computerized tomography angiography revealed a right-sided terminal internal carotid artery (ICA) occlusion, and the coronary angiogram depicted double vessel disease with a culprit lesion in the right coronary artery (RCA). The patient underwent mechanical thrombectomy for the ICA occlusion by an interventional neuroradiologist followed by the primary percutaneous coronary intervention of the culprit RCA by the interventional cardiologists in the same setting. Conclusion: A patient with concurrent AMI and AIS is a challenging situation to treat in the emergency department, and the treatment must be individualized for each patient.

Comparative transcriptomes reveal pro-survival and cytotoxic programs of mucosal-associated invariant T cells upon Bacillus Calmette-Guérin stimulation.

Mucosal-associated invariant T (MAIT) cells are protective against tuberculous and non-tuberculous mycobacterial infections with poorly understood mechanisms. Despite an innate-like nature, MAIT cell responses remain heterogeneous in bacterial infections. To comprehensively characterize MAIT activation programs responding to different bacteria, we stimulated MAIT cells with E. coli to compare with Bacillus Calmette-Guérin (BCG), which remains the only licensed vaccine and a feasible tool for investigating anti-mycobacterial immunity in humans. Upon sequencing mRNA from the activated and inactivated CD8+ MAIT cells, results demonstrated the altered MAIT cell gene profiles by each bacterium with upregulated expression of activation markers, transcription factors, cytokines, and cytolytic mediators crucial in anti-mycobacterial responses. Compared with E. coli, BCG altered more MAIT cell genes to enhance cell survival and cytolysis. Flow cytometry analyses similarly displayed a more upregulated protein expression of B-cell lymphoma 2 and T-box transcription factor Eomesodermin in BCG compared to E.coli stimulations. Thus, the transcriptomic program and protein expression of MAIT cells together displayed enhanced pro-survival and cytotoxic programs in response to BCG stimulation, supporting BCG induces cell-mediated effector responses of MAIT cells to fight mycobacterial infections.

Framework for Quality Assurance of Ultrahigh Dose Rate Clinical Trials Investigating FLASH Effects and Current Technology Gaps.

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials.

The "Ins and Outs" of Prostate Specific Membrane Antigen (PSMA) as Specific Target in Prostate Cancer Therapy.

Prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with metastasis, progression, and androgen independence. Because of its specificity, PSMA is a major target of prostate cancer therapy; however, detectable levels of PSMA are also found in other tissues, especially in salivary glands and kidney, generating bystander damage of these tissues. Antibody target therapy has been used with relative success in reducing tumor growth and prostate specific antigen (PSA) levels. However, since antibodies are highly stable in plasma, they have prolonged time in circulation and accumulate in organs with an affinity for antibodies such as bone marrow. For that reason, a second generation of PSMA targeted therapeutic agents has been developed. Small molecules and minibodies have had promising clinical trial results, but concerns about their specificity had arisen with side effects due to accumulation in salivary glands and kidneys. Herein we study the specificity of small molecules and minibodies that are currently being clinically tested. We observed a high affinity of these molecules for PSMA in prostate, kidney and salivary gland, suggesting that their effect is not prostate specific. The search for specific prostate target agents must continue so as to optimally treat patients with prostate cancer, while minimizing deleterious effects in other PSMA expressing tissues.

Effect of Imatinib treatment on renal anaemia in chronic myeloid leukemia patients.

PURPOSE: In this study, we investigate renal function and anaemia during imatinib treatment in patients with chronic myeloid leukaemia. METHODS: The patients with chronic myeloid leukaemia with chronic phase who had been treated with only imatinib for 12 months at Rajiv Gandhi Cancer Institute and Research Centre (New Delhi, India) were enrolled and prospectively analysed. The chronic renal impairment parameters, including estimated glomerular filtration rate and haemoglobin levels for anaemia from June 2020 to June 2022, were monitored in newly diagnosed in patients with chronic myeloid leukaemia-chronic phase. The data were analysed by SPSS software version 22. RESULTS: In total 55 patients with chronic myeloid leukaemia chronic phase who had been on imatinib for 12 months were monitored. The mean estimated glomerular filtration rate was significantly decreased (74 ± 14 to 59 ± 12 mL/min/1.73m2, p < 0.001) with a decrease in mean haemoglobin levels after 12 months (10.9 ± 2.01 to 9.0 ± 1.02, p < 0.004). The decreased estimated glomerular filtration rate was negatively correlated with haemoglobin levels after 1 year of imatinib administration (correlation coefficient = 0.892, R2 = 0.7976, p < 0.05). CONCLUSION: We recommended close monitoring of renal function and haemoglobin levels in patients with chronic myeloid leukaemia patients.

Evaluation of Sida cordifolia and Sida rhombifolia extracts in a rat model of streptozotocin-induced diabetic nephropathy.

BACKGROUND: Sida cordifolia and Sida rhombifolia are regarded as useful herbs as they have been shown to be effective, inexpensive and harmless in the prevention of diabetes, and are recognized as valuable therapeutic substances. OBJECTIVES: The purpose of this study was to assess the effect of S. cordifolia and S. rhombifolia in the treatment of diabetic nephropathy using a rat model. MATERIAL AND METHODS: Extracts of S. cordifolia and S. rhombifolia were obtained using the Soxhlet method. The hydroalcoholic extract solvent was used in the following proportions: 70:30, 50:50 and 80:20. The 80:20 hydroalcoholic extract was observed to be the most potent. The inhibitory effects of the extract were determined using the α-amylase assay. The most potent extract also underwent total flavonoid, phenolic and free radical scavenging tests, and was incorporated into an animal study. Diabetes was induced in rats by administering nicotinamide (NAD; 230 mg/kg) and streptozotocin (STZ; 65 mg/kg) intraperitoneally. In addition to a standard control of pioglitazone, the rats received extract dosages of 100 mg/kg/day or 200 mg/kg/day. Body weight, blood glucose, glycated hemoglobin (HbA1c), blood urea nitrogen (BUN), serum albumin, serum creatinine, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance were assessed at various time points. The animals also underwent histopathological examination to observe alterations induced by the treatment. RESULTS: Sida cordifolia was the most successful in lowering blood glucose and HbA1c levels. Renal function indices and antioxidant enzyme levels were regained in a dose-dependent manner. Furthermore, S. cordifolia (200 mg/kg/day) extract, similar to pioglitazone, inhibited the production of advanced glycation byproducts by the kidney. CONCLUSIONS: The effects of various S. cordifolia and S. rhombifolia extracts on rats with diabetic nephropathy were observed. Sida cordifolia may be further explored for the treatment of diabetic nephropathy and, due to its diverse nature, may be utilized for the treatment of a wide range of diseases, as it provided more significant findings.

Phytoremediation of Potentially Toxic Elements: Role, Status and Concerns.

Environmental contamination with a myriad of potentially toxic elements (PTEs) is triggered by various natural and anthropogenic activities. However, the industrial revolution has increased the intensity of these hazardous elements and their concentration in the environment, which, in turn, could provoke potential ecological risks. Additionally, most PTEs pose a considerable nuisance to human beings and affect soil, aquatic organisms, and even nematodes and microbes. This comprehensive review aims to: (i) introduce potentially toxic elements; (ii) overview the major sources of PTEs in the major environmental compartments; (iii) briefly highlight the major impacts of PTEs on humans, plants, aquatic life, and the health of soil; (iv) appraise the major methods for tackling PTE-caused pollution; (v) discuss the concept and applications of the major eco-technological/green approaches (comprising phytoextraction, rhizofiltration, phytostabilization, phytovolatilization, and phytorestoration); (vi) highlight the role of microbes in phytoremediation under PTE stress; and (vii) enlighten the major role of genetic engineering in advancing the phytoremediation of varied PTEs. Overall, appropriate strategies must be developed in order to stop gene flow into wild species, and biosafety issues must be properly addressed. Additionally, consistent efforts should be undertaken to tackle the major issues (e.g., risk estimation, understanding, acceptance and feasibility) in order to guarantee the successful implementation of phytoremediation programs, raise awareness of this green technology among laymen, and to strengthen networking among scientists, stakeholders, industrialists, governments and non-government organizations.

Molecular Docking of Bacterial Protein Modulators and Pharmacotherapeutics of Carica papaya Leaves as a Promising Therapy for Sepsis: Synchronising In Silico and In Vitro Studies.

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host's body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.