Radiosynthesis and in silico bioevaluation of 131 I-Sulfasalazine as a highly selective radiotracer for imaging of ulcerative colitis

xlomafota13 shared this article with you from Inoreader Radiosynthesis and in silico bioevaluation of <sup>131</sup> I-Sulfasalazine as a highly selective radiotracer for imaging of ulcerative colitis Via radioactive iodine Chem Biol Drug Des. 2021 Jul 27. doi: 10.1111/cbdd.13929. Online ahead of print. ABSTRACT This study demonstrated the tracking of ulcerative colitis, which is considered a stressful immune disease. Although there are many ways to test for this disease including dependence on gases, dyes, and painful anal endoscopy, these treatment modalities have many disadvantages. Hence, it is the utmost need of time to discover new methods to detect this chronic immune disease and to avoid the d efects of traditional methodologies. Sulfasalazine (SSD) was labeled with iodine-131 (Half-life: 8 days, Energy: 971 keV) under optimum reaction conditions including the amount of reducing agent, pH factor, Chloramine-T (Ch-T) amount, and incubation period. Characterization was performed using 1 H/ 13 C-NMR, ESI-MS, and HPLC (UV/ Radio) techniques. The biodistribution study was performed in normal and ulcerative mice models as well as in silico molecular docking study was performed to evaluate the possible mechanism of action to target peroxisome proliferator-activated receptor gamma (PPARγ). The high radiolabeling yield of [131 I]-sulfasalazine ([131 I]-SSD) was achieved ≥ 90% through the direct labeling method with radioactive iodine-131 in the presence of chloramine-T (100 μg). The radiotracer [131 I]-SSD was observed to be stable in normal saline and freshly eluted serum up to 12 h at ambient temperature (37°C ± 2°C). The radiotracer [131 I]-SSD showed the highest uptake in the targeted organ (i.e. ulcerative colon) which was observed to be ≥ 75% injected dose per gram (% ID/g) organ for 24 h post-injection (p.i). Furthermore, in silico data collected from molecular modeling analysis of SSD and [131 I]-SSD with antimicrobial protein (PDB code: 3KEG) and peroxisome proliferator-activated receptor-gamma (PPARγ) (PDB code: 4XTA) showed azoreductase activity and high binding potential for PPAR-γ site, respectively. The results of biological studies obtained in this study enlighten the usefulness of radiotracer [131 I]-SSD as a potential imaging agent for ulcerative colitis. PMID:34314572 | DOI:10.1111/cbdd.13929 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prevalence of Hashimoto Thyroiditis in Adults With Papillary Thyroid Cancer and Its Association With Cancer Recurrence and Outcomes

xlomafota13 shared this article with you from Inoreader Prevalence of Hashimoto Thyroiditis in Adults With Papillary Thyroid Cancer and Its Association With Cancer Recurrence and Outcomes Via radioactive iodine JAMA Netw Open. 2021 Jul 1;4(7):e2118526. doi: 10.1001/jamanetworkopen.2021.18526. ABSTRACT IMPORTANCE: Hashimoto thyroiditis (HT) has been suggested to be associated with papillary thyroid cancer (PTC) development. However, its association with PTC progression remains unclear. OBJECTIVE: To examine the association between HT and PTC presentation and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a review of patients aged 18 to 75 years who had pathologically confirmed PTC treated at a single center in China from January 1, 2001, to December 31, 2014. Data analysis was performed from November 1 to December 31, 2020. EXPOSURES: Coexistent HT was defined according to evaluation of postoperative paraffin sections. MAIN OUTCOMES AND MEASURES: The primary outcome was the association of HT with PTC-related mortality, assessed using Cox proportional hazards regression models. The secondary outcome was the association of HT with aggressive characteristics and structural recurrence of PTC, assessed using logistic regression and Cox proportional hazards regression with and without adjustment for related factors. RESULTS: Of 9210 patients with PTC (mean [SD] age, 43.6 [12.0] years; 6872 [75%] women) included in the analysis, 1751 (19%) had HT. In the logistic regression model, HT was negatively associated with frequencies of primary tumor size of 4 cm or greater (adjusted odds ratio [aOR], 0.20; 95% CI , 0.12-0.33; P < .001), gross extrathyroidal extension (aOR, 0.44; 95% CI, 0.36-0.54; P < .001), extranodal extension (aOR, 0.66; 95% CI, 0.55-0.80; P < .001), and distant metastasis (aOR, 0.17; 95% CI, 0.04-0.71; P = .02). After a median follow-up of 85 months (range, 12-144 months), 131 PTC-related deaths were identified in the cohort; 2 patients who died had HT. Patients with HT had significantly superior outcomes compared with patients without HT in terms of unadjusted 10-year disease-specific survival (99.9% vs 96.6%; log-rank P < .001) and recurrence-free survival (92.0% vs 87.6%; log-rank P = .001). After adjusting for sex, age, primary tumor size, extrathyroidal extension, lymph node metastasis, distant metastasis, extent of surgery, and radioactive iodine ablation, HT was associated with decreased PTC-related mortality (hazard ratio [HR], 0.19; 95% CI, 0.05-0.76; P = .02). Stratified analysis showed that HT was associated with less frequent structural recurrence in patients with extrathyroidal extension (HR, 0.52; 95% CI, 0.38-0.71; P < .001; P = .002 for interaction) or after total thyroidectomy (HR, 0.50; 95% CI, 0.35-0.69; P < .001; P = .009 for interaction). CONCLUSIONS AND RELEVANCE: In this cohort study, patients with coexistent HT had less aggressive characteristics at presentation and better outcomes of PTC than did patients without HT. The findings suggest that autoimmune thyroiditis has a protective role in association with thyroid cancer. PMID:34313737 | DOI:10.1001/jamanetworkopen.2021.18526 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Designable Assembly of Aluminum Molecular Rings for Sequential Confinement of Iodine Molecules

xlomafota13 shared this article with you from Inoreader Designable Assembly of Aluminum Molecular Rings for Sequential Confinement of Iodine Molecules Via radioactive iodine Angew Chem Int Ed Engl. 2021 Jul 27. doi: 10.1002/anie.202107227. Online ahead of print. ABSTRACT Although numerous adsorbent materials have been reported for radioactive iodine capture, demands for the development of new absorbents that are economically viable and featured with reliable synthetic protocols still exist. Herein, in this paper, a coordination-driven self-assembly strategy towards adsorbents for sequential confinement of iodine molecules is reported. It should be noti ced that these adsorbents are versatile heterometallic frameworks constructed from aluminum molecular rings of varying size, flexible copper ions and conjugated carboxylate ligands. Additionally, these materials can quickly remove iodine from cyclohexane solutions with a high removal rate (98.8%) and considerable loading capacity (555.06 mg/g). Heterometallic frameworks provided distinct pore sizes and binding sites toward iodine molecules and realize crystallographic visualization concerning sequential confinement of iodine molecules. This work not only sets up a bridge between molecular rings and infinite porous networks but also reveals molecular details for the underlying host-guest binding interactions at crystallographic resolution. PMID:34314080 | DOI:10.1002/anie.202107227 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Morphological analysis of interstitial cells in murine epididymis using light microscopy and transmission electron microscopy

xlomafota13 shared this article with you from Inoreader Morphological analysis of interstitial cells in murine epididymis using light microscopy and transmission electron microscopy Via histochem Acta Histochem. 2021 Jul 20;123(6):151761. doi: 10.1016/j.acthis.2021.151761. Online ahead of print. ABSTRACT Smooth muscle contraction of the epididymis plays an important role in sperm transport. Although PDGFRα-positive interstitial cells (PDGFRα (+) ICs) are thought to be involved in controlling smooth muscle movement via intercellular signaling, they have not yet been reported to date in the epididymis. Therefore, we aimed to investigate the morphological characterist ics of PDGFRα (+) ICs in the interstitial space of the murine epididymis. Immunohistochemistry showed that PDGFRα (+) ICs co-labeled with CD34 (PDGFRα (+) CD34 (+) ICs were distributed in the interstitial space of the murine epididymis from the initial segment (IS) to the cauda of the epididymis. PDGFRα (+) ICs that were not co-labeled with CD34 (PDGFRα (+) CD34 (-) ICs) were observed just beneath the epithelium from the corpus to the cauda but not in the IS. Both types of PDGFRα (+) ICs were in close proximity to each other as well as the surrounding nerves and macrophages. In addition, PDGFRα (+) CD34 (-) ICs beneath the epithelium were also in close proximity to the basal cells. Using transmission electron microscopy, we identified ICs that possessed elongated and woven cellular processes and were in close proximity to each other, surrounding the cells in the interstitial space. In the murine epididymis, it is suggested that there are two subtypes of ICs that show differen t distribution patterns depending on the segment, which may reflect segmental differences in mechanisms of sperm transport, forming a cellular network by physical interactions in the murine epididymis. PMID:34298316 | DOI:10.1016/j.acthis.2021.151761 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

TNF-alpha May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis

xlomafota13 shared this article with you from Inoreader TNF-alpha May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis Via radioactive iodine Cancers (Basel). 2021 Jul 19;13(14):3609. doi: 10.3390/cancers13143609. ABSTRACT Autoimmune thyroiditis (AIT) may impair radioiodine (131I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of 131I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tiss ue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after 131I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after 131I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after 131I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = -0.62, p < 0.001 and r = -0.58, p < 0.001). Our results demonstrate that TNF-α ma y exert different antitumor effects in response to 131I therapy depending on the patient's immune profile. PMID:34298820 | DOI:10.3390/cancers13143609 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pre-Therapeutic Measurements of Iodine Avidity in Papillary and Poorly Differentiated Thyroid Cancer Reveal Associations with Thyroglobulin Expression, Histological Variants and Ki-67 Index

xlomafota13 shared this article with you from Inoreader Pre-Therapeutic Measurements of Iodine Avidity in Papillary and Poorly Differentiated Thyroid Cancer Reveal Associations with Thyroglobulin Expression, Histological Variants and Ki-67 Index Via radioactive iodine Cancers (Basel). 2021 Jul 20;13(14):3627. doi: 10.3390/cancers13143627. ABSTRACT Papillary thyroid cancer (PTC) and poorly differentiated thyroid cancer (PDTC) are treated with radioiodine to reduce recurrence and to treat the spread of disease. Adequate iodine accumulation in cancer tissue, iodine avidity, is important for treatment effect. This study investigated which clinical and histological tumour characteristics correlate with avidity. To quantify avidity in cancer tissue, t racer amounts of iodine-131 were given to 45 patients with cytologically confirmed thyroid cancer. At pathology grossing, representative samples of tumour and lymph nodes were taken and subjected to radioactivity quantification ex vivo to determine avidity. Afterwards, samples underwent extended pathology work-up and analysis. We found that tumoural Tg expression and Ki-67 index were correlated with avidity, whereas tumour size and pT stage were not. The histological variant of thyroid cancer was also correlated with iodine avidity. Variants associated with worse clinical prognoses displayed lower avidity than variants with better prognoses. This work provides new information on which tumours have low iodine avidity. Lower avidity in aggressive histological PTC variants may explain their overall poorer prognoses. Our findings also suggest that radioiodine dosage could be adapted to Tg expression, Ki-67 index or histological variant instead of pT stage, potentially improving the effi cacy of radioiodine therapy. PMID:34298840 | DOI:10.3390/cancers13143627 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Novel Reagent for Radioiodine Labeling of New Chemical Entities (NCEs) and Biomolecules

xlomafota13 shared this article with you from Inoreader A Novel Reagent for Radioiodine Labeling of New Chemical Entities (NCEs) and Biomolecules Via radioactive iodine Molecules. 2021 Jul 18;26(14):4344. doi: 10.3390/molecules26144344. ABSTRACT Radioiodine labeling of peptides and proteins is routinely performed by using various oxidizing agents such as Chloramine T, Iodobeads, and Iodogen reagent and radioactive iodide (I-), although some other oxidizing agents were also investigated. The main objective of the present study was to develop and test a novel reagent, inorganic monochloramine (NH2Cl), for radioiodine labeling o f new chemical entities and biomolecules which is cost-effective, easy to make and handle, and is selective to label amino acids, peptides, and proteins. The data presented in this report demonstrate that the yields of the non-radioactive iodine labeling reactions using monochloramine are >70% for an amino acid (tyrosine) and a cyclic peptide (cyclo Arg-Gly-Asp-d-Tyr-Lys, cRGDyK). No evidence of the formation of N-chloro derivatives in cRGDyK was observed, suggesting that the reagent is selective in iodinating the tyrosine residue in the biomolecules. The method was successfully translated into radioiodine labeling of amino acid, a peptide, and a protein, Bovine Serum Albumin (BSA). PMID:34299619 | DOI:10.3390/molecules26144344 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.