16 research outputs found
Bridging the gap:from methodological developments towards clinical implementation of imaging biomarkers in lung and breast cancer
Development of new organic-inorganic, hybrid bionanocomposite from cellulose and clay for enhanced removal of Drimarine Yellow HF-3GL dye
© 2020 Elsevier B.V. Cellulose/clay composites were prepared and applied for the adsorption of Drimarine Yellow HF-3GL direct dye. The prepared composites were characterized by FTIR, TGA, EDX, SEM and XRD techniques. Bagasse was used as a cellulose source, while clay was obtained from local source, which was modified chemically before composite preparation. Adsorption efficiencies were compared of composite I and II as a function of contact time, temperature, pH, initial dye concentration and composite dose. Non-linear kinetic and equilibrium isotherm employed and dye adsorption data fitted well to pseudo-second order kinetics model. Among isotherms, the Redlich-Peterson isotherm well defined the sorption process of dye on to composites. Thermodynamic factors (ΔS°, ΔH° and ΔG°) revealed that the sorption process was spontaneous, exothermic and feasible. Cellulose/clay composite I and II removed 88.64% and 89.95% dye with 60 min at pH 2 and 30 °C, respectively. For reusability, desorption was performed using different eluting agents and NaOH showed higher desorption efficiency. For the treatment of wastewater, the developed composites were applied to textile effluents and color removal of (90–96.07%) and (97–98.23%) was achieved using cellulose/clay composite I and II, respectively. The results showed that cellulose/clay composite are efficient for the removal dyes and could possibly be used for the treatment of textile effluents
R : Lithium-mediated electrochemical dinitrogen reduction reaction
The Haber–Bosch process is the dominant approach for NH3 production today, but the process has to be maintained at energy-intensive high temperatures and pressures. Li-mediated electrocatalytic dinitrogen reduction reaction (eN2RR) could instead enable sustainable and green NH3 production at ambient conditions. Lithium mediators realize the synthesis of NH3via the formation of Li3N, and thus lower the energy required for the direct cleavage of N2. There has now been a surge of interest in devising approaches to optimize the NH3 yield rate and faradaic efficiency of the eN2RR process by employing different catalysts as well as electrolytes. This review discusses the recent advances in the field of the Li-mediated eN2RR along with the latest insights into the proposed catalytic mechanisms. Moreover, it also highlights the state-of-the-art reported electrocatalysts and electrolytes that have revolutionized the field of the Li-mediated eN2RR. In addition to the above, our review provides a critical overview of certain limitations and a future prospectus that will provide a way forward to explore this area. Keywords: Nitrogen reduction reaction; Ammonia; Electrocatalysis; Lithium; Reaction mechanism
[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant
PURPOSE: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER+ breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.PATIENTS AND METHODS: In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS).RESULTS: The HS and PFS in the entire group did not correlate (n=16, Spearman's rho, P=0.06), but patients with a low HS (<25.0%, n=4) had a PFS of >5 months whereas patients with no [18F]FES uptake (HS 100.0%, n =3) had a PFS of <2 months. [18F]FES uptake was not affected by ESR1 mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤1-2 half-lives of rintodestrant whereas it restored in patients scanned ≥5 days after end of treatment.CONCLUSION: Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs.</p
Effect of escitalopram and carbidopa on bone markers in Wistar rats: a preliminary experimental study
In view of the opposite effects of gut and brain serotonin in bone, the key role of Wnt β/catenin pathway in osteoblastic proliferation and the controversial bony effects of selective serotonin reuptake inhibitors antidepressants, the present study investigated the effects of escitalopram alone and in combination with carbidopa (to block gut-derived serotonin) on markers of bone turnover and Wnt signaling and micro-CT in male Wistar rats. Escitalopram (2.0 mg/kg, p.o.) and carbidopa (10 mg/kg, p.o.) were administered daily for 40 days following which indicators of reduced (dickkopf-1, sclerostin), and increased (alkaline phosphatase) bone formation and bone resorption markers (receptor activator of nuclear factor κB ligand, tartrate-resistant acid phosphatase 5b) were determined. Our results indicated that escitalopram adversely affected bone as indicated by reduced bone formation and enhanced bone resorption. Further, the effects of escitalopram on bone formation were possibly mediated through gut serotonin while the mechanisms responsible for effects on resorption seem unrelated to gut serotonin. The promising effects of carbidopa on bone formation, as observed in our study, open up exciting possibilities for this drug requiring further investigations
Pitavastatin ameliorates myocardial damage by preventing inflammation and collagen deposition via reduced free radical generation in isoproterenol-induced cardiomyopathy
Pitavastatin inhibits 3 hydroxy 3 methyl glutaryl coenzyme A (HMGCoA) reductase enzyme, preventing cholesterol synthesis along with elevating high density apolipoprotein A1 (Apo-A1). The present study was designed to evaluate cardioprotective potential of pitavastatin at 1 mg/kg/day and 3 mg/kg/day dose for 14 days in low dose isoproterenol (ISO) (5 mg/kg/day for 7 consecutive days) induced myocardial damage. ISO administration induced significant reduction in endogenous antioxidant enzymes like reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and raised thiobarbituric acid reactive substances (TBARS) indicating activated lipid peroxidation. Along with this, a significant increase in level of cardiac injury biomarkers vie, creatine kinase (CK-MB), lactate dehydrogenase (LDH), aspartate amino transferase (AST), tumor necrosis factor (TNF-α) and transforming growth factor (TGF-β) as well as brain natriuretic peptide (BNP). Histological examination also revealed marked myocardial tissue damage in ISO treated rats. However, pretreatment with pitavastatin (3 mg/kg/day) significantly maintained nearly normal levels of cardiac biomarkers and oxidant antioxidant status as well as lipid peroxidation in ISO induced MI rats. Cardiac histological assessment and infarct size assessment also showed marked reduction in myocardial architecture alteration including infarct size as well as collagen deposition by pitavastatin that strongly supported biochemical findings. These observations strongly corroborate that pitavastatin prevents myocardial damages via up regulation of endogenous oxidants along with its hypocholesterolemic activity
A facile approach to investigate the charge storage mechanism of MOF/PANI based supercapattery devices
Single-atom catalysts for electrochemical N2 reduction to NH3
The increasing demand for clean energy and growing concerns regarding environmental sustainability have led to greater attention devoted toward the production of clean fuels via green chemistry. In this respect, ammonia is a green alternative to fossil fuels and can serve as a clean energy source. There is now great interest in realizing the electrochemical reduction in atmospheric nitrogen (N2) for cheap, environmentally friendly and reliable ammonia (NH3) production worldwide. However, the robustness of the triple bond in N2 and the low efficiency of candidate catalysts limit the utility of this conversion. Single atom catalysts have been found to be more effective than nanoparticles due to their unique properties, and thus have been studied extensively for the nitrogen reduction reaction. In this review, we have covered the recent advances in design and synthesis of noble metal and non-noble metal single atom catalysts for the electrochemical reduction in nitrogen during the years 2018–2022. The catalyst efficiencies, with reference to coordination preferences and theoretical studies have been discussed. Moreover, we also provide insights into the current challenges and some considerations for further future studies
Mutational analysis of hemoglobin genes and functional characterization of detected variants, through in-silico analysis, in Pakistani beta-thalassemia major patients
Abstract Thalassemia is one of the most prevalent genetic disorders worldwide. The present study aimed to explore the mutational spectrum of all hemoglobin (HB) encoding genes and to identify the potentially damaging and pathogenic variants in the beta (β)-thalassemia major patients and thalassemia minor carriers of Southern Punjab, Pakistan. A total of 49 β-thalassemia major patients and 49 carrier samples were screened for the identification of HBA1, HBA2, HBB, HBD, HBE1, HBG1 and HBG2 variants by NGS. PCR was performed for the amplification of HB encoding genes and the amplified product of 13 patients and 7 carrier samples were processed for the Sanger sequencing. Various bioinformatics tools and databases were employed to reveal the functional impact and pathogenicity potential of the observed variants. Results depicted a total of 20 variants of HB-related genes by NGS and 5 by Sanger sequencing in thalassemia patients. While 20 variants by NGS and 3 by Sanger were detected in carriers. Few known genetic variants of HB-encoding genes are being reported for the first time in Pakistani thalassemia patients and carriers. However, two novel HBB variants c.375A>C (p.P125P) and c.*61T>G and a novel variant of HBE1 (c.37A>T (p.T13S)) were also documented. Pathogenicity analysis predicted the pathogenic potential of HBB variants (c.47G>A (p.W16*), c.27-28insG (p. S10fs), and c.92+5G>C) for β thalassemia. The study of functional impact indicated that these HBB variants result in the premature termination of translation leading to the loss of functional β-globin protein. It is therefore suggested that the pathogenic HBB variants, identified during present study, can be employed for the diagnosis, carrier screening, and planning therapy of thalassemia
Biodistribution of 18F-FES in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant (G1T48), a Novel Selective ER Degrader
16α-18F-fluoro-17β-estradiol (18F-FES) is a PET tracer characterizing the expression of the estrogen receptor (ER). Because therapy can interfere with the kinetics and biodistribution of 18F-FES, the aim of this study was to describe the biodistribution of 18F-FES in patients with metastatic ERpositive (ER1) breast cancer undergoing treatment with rintodestrant (G1T48), a novel selective ER degrader. Methods: Eight patients underwent 18F-FES PET/CT imaging at baseline, 4-6 wk during treatmentwith rintodestrant (interim), and after treatment. After intravenous administration of 200 MBq (±10%) of 18F-FES, a 50-min dynamic PET/CT scan of the thorax was obtained, followed by a whole-body PET/CT scan 60 min after injection. Blood samples were drawn for measuring whole blood and plasma activity concentration and the parent fraction of 18F-FES. Volumes of interest were placed in the aorta ascendens and in healthy tissues on both dynamic and whole-body PET scans. SUVs and targetto- blood ratios (TBRs) were calculated. Areas under the curve (AUCs) of input functions and time-activity curves were calculated as a measure of uptake in different regions. Results: 18F-FES concentration in whole blood (and plasma) significantly (P < 0.05) increased at interim with median AUCs of 96.6, 116.6, and 110.3 at baseline, interim, and after treatment, respectively. In ER-expressing tissues, that is, the uterus and the pituitary gland, both SUV and TBR showed high 18F-FES uptake at baseline, followed by a decrease in uptake at interim (uterus: SUV 250.6% and TBR 258.5%; pituitary gland: SUV 239.0% and TBR 248.3%), which tended to return to baseline values after treatment (uterus: SUV 221.5% and TBR 237.9%; pituitary gland: SUV 214.2% and TBR 226.0%, compared with baseline). In other healthy tissues, tracer uptake remained stable over the 3 time points. Conclusion: The biodistribution of 18F-FES is altered in blood and in ER-expressing healthy tissues during therapy with rintodestrant. This indicates that rintodestrant alters the kinetics of the tracer, possibly affecting interpretation and quantification of 18F-FES uptake. Of note, 6 d or more after treatment with rintodestrant ended, the biodistribution returned to baseline values, consistent with recovery of ER availability after washout of the drug