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Levels of reactive oxygen species (ROS) are the primary determinants of pulmonary fibrosis. It was discovered that antioxidants can ameliorate pulmonary fibrosis caused by prolonged paraquat (PQ) exposure. However, research on the precise mechanisms by which antioxidants influence the signaling pathways implicated in pulmonary fibrosis induced by paraquat is still insufficient. This research utilized a rat model of pulmonary fibrosis induced by PQ to examine the impacts of Silibinin (Sil) and cinnamic acid (CA) on pulmonary fibrosis, with a specific focus on pro-fibrotic signaling pathways and ROS-related autophagy. Lung injury induced by paraquat was demonstrated to be associated with oxidative stress and inflammation of the lungs, downregulated (miR-193a), and upregulated PI3K/AKT/mTOR signaling lung tissues. Expression levels of miR-193a were determined with quantitative real-time PCR, protein level of protein kinase B (Akt), and phosphoinositide 3-Kinase (PI3K) which were determined by western blot analysis. Hydroxyproline levels (HYP) and transforming growth factor-β1 (TGF-β1) were measured by ELISA, malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GSH), and catalase and were measured in lung tissue homogenates colorimetrically using spectrophotometer. Long-term exposure to paraquat resulted in decreased PI3K/AKT signaling, decreased cell autophagy, increased oxidative stress, and increased pulmonary fibrosis formation. Silibinin and cinnamic acid also decreased oxidative stress by increasing autophagy and miR-193a expression, which in turn decreased pulmonary fibrosis. These effects were associated by low TGF-β1. Silibinin and cinnamic acid inhibited PQ-induced PI3K/AKT by stimulating miR-193-a expression, thus attenuating PQ-induced pulmonary fibrosis., (© 2024. The Author(s).)

Mirtazapine (MZPc) is an antidepressant drug which is approved by the FDA. It has low bioavailability, which is only 50%, in spite of its rapid absorption when orally administered owing to high first-pass metabolism. This study was oriented towards delivering intranasal (IN) mirtazapine by a direct route to the brain by means of preparing lipid nanocapsules (LNCs) as a targeted drug delivery system. MZP-LNCs were constructed by solvent-free phase inversion temperature technique applying D-Optimal mixture design to study the impact of 3 formulation variables on the characterization of the formulated nanocapsules. Independent variables were percentage of Labrafac oil, percentage of Solutol and percentage of water. Dependent variables were particle size, polydispersity index (PDI), Zeta potential and solubilization capacity. Nanocapsules of the optimized formula loaded with MZP were of spherical shape as confirmed by transmission electron microscopy with particle diameter of 20.59 nm, zeta potential of - 5.71, PDI of 0.223 and solubilization capacity of 7.21 mg/g. The in vivo pharmacokinetic behavior of intranasal MZP-LNCs in brain and blood was correlated to MZP solution after intravenous (IV) and intranasal administration in mice. In vivo biodistribution of the drug in mice was assessed by a radiolabeling technique using radioiodinated mirtazapine ( 131 I-MZP). Results showed that intranasal MZP-LNCs were able to deliver higher amount of MZP to the brain with less drug levels in blood when compared to the MZP solution after IV and IN administration. Moreover, the percentage of drug targeting efficiency (%DTE) of the optimized MZP-LNCs was 332.2 which indicated more effective brain targeting by the intranasal route. It also had a direct transport percentage (%DTP) of 90.68 that revealed a paramount contribution of the nose to brain pathway in the drug delivery to the brain., (© 2024. The Author(s).)

Perturbations produced by ionizing radiation on intestinal tissue are considered one of highly drastic challenges in radiotherapy. Animals were randomized into five groups. The first group was allocated as control, and the second was subjected to whole body γ-irradiation (10 Gy). The third was administered HA NP (17.6 mg/kg/day; i.p.) and then irradiated. The fourth one received MitoQ (2 mg/kg/day; i.p.) and then irradiated. The last group received MitoQ/HA NP (2 mg/kg/day; i.p.) for 5 days prior to irradiation. Mice were sacrificed a week post-γ-irradiation for evaluation. MitoQ/HA NP ameliorated mitochondrial oxidative stress as indicated by rising (TAC) and glutathione peroxidase and decreasing malondialdehyde, showing its distinguished antioxidant yield. That impacted the attenuation of apoptosis, which was revealed by the restoration of the anti-apoptotic marker and lessening proapoptotic caspase-3. Inflammatory parameters dwindled via treatment with MitoQ/HA NP. Moreover, this new NP exerts its therapeutic action through a distinguished radioprotective pathway (Hmgb1/TLR-4.) Subsequently, these antioxidants and their nanoparticles conferred protection to intestinal tissue as manifested by histopathological examination. These findings would be associated with its eminent antioxidant potential through high mitochondria targeting, enhanced cellular uptake, and ROS scavenging. This research underlines MitoQ/HA NP as a new treatment for the modulation of intestinal damage caused by radiotherapy modalities., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, β-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients., Aim: Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction., Patients & Methods: Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA., Results: Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity., Conclusion: Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. WAEL HAFEZ. All authors declare no competing financial interests., (© 2024 The Authors.)

Background: Orlistat (ORL) is an effective irreversible inhibitor of the lipase enzyme, and it possesses anticancer effects and limited aqueous solubility. This study was designed to improve the aqueous solubility, oral absorption, and tissue distribution of ORL via the formulation of nanocrystals (NCs)., Methods: ORL-NC was prepared using the liquid antisolvent precipitation method (bottom-up technology), and it demonstrated significantly improved solubility compared with that of the blank crystals (ORL-BCs) and untreated ORL powder. The biodistribution and relative bioavailability of ORL-NC were investigated via the radiolabeling technique using Technetium-99m ( 99m Tc). Female Swiss albino mice were used to examine the antitumor activity of ORL-NC against solid Ehrlich carcinoma (SEC)-induced hepatic damage in mice., Results: The prepared NCs improved ORL's solubility, bioavailability, and tissue distribution, with evidence of 258.70% relative bioavailability. In the in vivo study, the ORL-NC treatment caused a reduction in all tested liver functions (total and direct bilirubin, AST, ALT, and ALP) and improved modifications in liver sections that were marked using hematoxylin and eosin staining (H&E) and immunohistochemical staining (Ki-67 and ER-α) compared with untreated SEC mice., Conclusions: The developed ORL-NC could be considered a promising formulation approach to enhance the oral absorption tissue distribution of ORL and suppress the liver damage caused by SEC.

Brain abscess is a life-threatening condition that requires a timely and accurate diagnosis. In this study, linezolid, an oxazolidinone antibiotic, was labeled with technetium-99m according to the stannous chloride method. The labeling reaction factors were studied and optimized to achieve a high yield (97.4 ± 2.3%). The 99m Tc-linezolid was radio- and physico-chemically characterized to assess its suitability as a radiopharmaceutical for the brain. In-silico docking to target peptidyltransferase showed an optimal binding fit (energy = -66.6 Kcal/mol). The complex was biologically evaluated in-vitro using binding assays in alive and heat-killed bacteria and in-vivo in an MRSA brain infection model. All results suggested that the labeled complex could potentially be a new nuclear imaging agent to diagnose and localize brain abscesses specifically., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aims to develop an Excel programming model to formulate feed for Nile tilapia ( Oreochromis niloticus ), mainly for small- and medium-sized fish feed manufacturers. The model allows users to formulate the least costly balanced diet of Nile tilapia species, giving them the ability to choose a specific ingredient in the formulation according to the realities of the local environment: space-temporary availability of ingredients, prices and nutritional quality. Computer programming of a database of 25 locally available feed components was carried out using the Excel Solver Add-in and Excel IF mathematical functions to incorporate/delete specific ingredients in real time in accordance with user objectives. The theoretical characteristics of the least-cost balanced diets performed were within the margin of the nutrients requirement of the target fish size with protein levels of 35 per cent (fry diet: $1.07/kg), 32 per cent (fingerlings diet: $0.48/kg), 29 per cent (growth diet: $0.43/kg) and 27.12 per cent (final diet: $0.39/kg). The digestible energy of these diets was between 3016.5 ± 93.8 kcal. In addition, the model shows that an increase in soya meal prices by 75 per cent led the local feed industry to rely on imported fish meals, as the number included reached 52.28 per cent. However, the cost of the diet margin did not vary significantly. Nevertheless, it would be important to test the balanced diet developed with the model before production and scaling., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In this study, two new series of 3-cyanopyridinones ( 3a-e ) and 3-cyanopyridines ( 4a-e ) were synthesized and evaluated for their cytotoxicity and Pim-1 kinase inhibitory activity adopting 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and in vitro Pim-1 kinase inhibition assay, respectively. Most of the tested compounds revealed promising cytotoxicity against HepG-2, HCT-116, MCF-7, and PC-3 cell lines. Among them, compounds 4c and 4d showed more potent cytotoxicity against the HePG2 cell line with IC 50 = 8.02 ± 0.38 and 6.95 ± 0.34 μM, respectively, than that of the reference 5-FU (IC 50 = 9.42 ± 0.46 μM). Moreover, compound 4c was more potent against HCT-116 (IC 50 = 7.15 ± 0.35 μM) than 5-FU (IC 50 = 8.01 ± 0.39 μM), while compound 4d with IC 50 = 8.35 ± 0.42 μM displayed comparable activity to that of the reference drug. Furthermore, high cytotoxic activity was manifested by compounds 4c and 4d against MCF-7 and PC3 cell lines. Our results have also indicated that compounds 4b , 4c , and 4d elicited remarkable inhibition of Pim-1 kinase; 4b and 4c showed equipotent inhibitory activity to that of the reference quercetagetin. Meanwhile, 4d displayed IC 50 = 0.46 ± 0.02 μM, showed the best inhibitory activity among the tested compounds, and was more potent than quercetagetin (IC 50 = 0.56 ± 0.03 μM). For optimization of the results, docking study of the most potent compounds 4c and 4d in the Pim-1 kinase active site was carried out and compared with both quercetagetin and the reported Pim-1 inhibitor A ( VRV ), and the results were consistent with those of the biological study. Consequently, compounds 4c and 4d are worthy of further investigations toward the discovery of Pim-1 kinase inhibitors as drug candidates for cancer therapy. Compound 4b was successfully radiolabeled with radioiodine-131, and its biodistribution in Ehrlich ascites carcinoma (EAC)-bearing mice showed more observable uptake in tumor sites, and hence, it can be introduced as a new radiolabeled agent for tumor imaging and therapy., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: The most prevalent cancer in Egypt is hepatocellular carcinoma (HCC) mainly due to the infection with the hepatitis C virus. So it is critical to find sensitive biomarkers for early diagnosis of HCC and avoid post-operation tumor recurrence. Therefore, this research was designed to demonstrate the circSERPINA3 role in the regulation of microRNA-944 gene expression in HCV-related HCC cases and compare these results with circSERPINA3 and microRNA-944 gene expression levels in HCV-infected patients., Methodology: Study participants were divided into three groups: healthy controls, HCV- infected, and HCV-induced HCC patients. The gene expression levels of circSERPINA3 and microRNA-944 were evaluated using Real-Time qPCR. Then the immunoblotting procedure was applied to measure the serum levels of MDM2 and E-cadherin besides, the serum concentration levels of glypican-3 and alpha-fetoprotein were measured by sandwich ELISA., Results: The gene expression level of circSERPINA3 was significantly upregulated in both HCV-infected and HCC patients causing suppression of the antitumor effect of miR-944 and showing a lower 1-year survival rate than the participants who had low circSERPINA3 gene expression levels. Subsequently, the miR-944 downstream protein, MDM2 was remarkably upregulated, exaggerating the metastasis and oxidative stress in HCC cases. Additionally, the results confirmed the downregulation of microRNA-944 improved the progression of viral hepatitis C cases to hepatocarcinogenesis through the significantly increased serum level of the metastatic marker, E-cadherin. Although alpha-fetoprotein is a common diagnostic marker used in the diagnosis of HCC, our results showed that glypican-3 had greater sensitivity and specificity and positively correlated to the IGF-1 signaling pathway of HCC cases. Moreover, the gene expression levels of circSERPINA3 and E-cadherin in both the HCV and HCV-induced HCC were significantly positively correlated., Conclusion: circSERPINA3 and miR-944 were sensitive molecular markers for early diagnosis of HCC and could be prospective treatment targets for HCV-infected patients to avoid tumor recurrence in HCC cases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

In this study, the mechanism of diazinon adsorption on single-walled carbon nanotubes (SWNTs), as well as multi-walled carbon nanotubes (MWNTs), was investigated using molecular modelling. Determination of the lowest energy sites of different types of carbon nanotubes (CNTs) was demonstrated. The adsorption site locator module was used for this purpose. It was found that the 5-walled CNTs are the best MWNTs for diazinon elimination from water due to their higher interactions with diazinon. In addition, the adsorption mechanism in SWNT and MWNTs was determined to be wholly adsorption on the lateral surface. It is because the geometrical size of diazinon molecules is larger than the inner diameter of SWNT and MWNTs. Furthermore, the contribution of diazinon adsorption on the 5-wall MWNTs was the highest, for the lowest diazinon concentration in the mixture., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The optimization of the radiolabeling yield of carvedilol with iodine-131 was described. Dependence of the labeling yield of [ 131 I]iodocarvedilol on the concentration of carvedilol, chloramine-T content, pH of the reaction mixture and reaction time was studied in details. Carvedilol was labeled with iodine-131 at pH 6 with a labeling yield of 92.6 ± 2.77% by using 100 µg carvedilol, 200 µg chloramin-T (CAT) and 30 min reaction time. The formed [ 131 I]iodocarvedilol was nearly stable for a time up to one day. Biodistribution of [ 131 I]iodocarvedilol was investigated in experimental animals. [ 131/123 I]iodocarvedilol was located in the heart with a concentration of 19.6 ± 0.41% of the injected dose at 60 min post injection. It has a high heart uptake and heart to liver ratio, both of which are beneficial for high-quality SPECT (single-photon emission computerized tomography) myocardial imaging. [ 131/123 I]iodocarvedilol solve most the drawbacks of the FDA (Food and Drug Administration) approved 99m Tc-sestamibi., (© 2023. The Author(s).)

Purpose: The present investigation aims to develop and evaluate a radiopharmaceutical for targeting and assessing β-cells mass based on gliclazide, an antidiabetic drug that specifically binds the sulfonylurea receptor unique to the β-cells of the pancreas., Methods: Conditions were optimized to radiolabel gliclazide with radioiodine via electrophilic substitution reaction. Then, it was formulated as a nanoemulsion system using olive oil and egg lecithin by hot homogenization followed by ultrasonication. The system was assessed for its suitability for parenteral administration and drug release. Then, the tracer was evaluated in silico and in vivo in normal and diabetic rats., Results and Conclusions: The labeled compound was obtained with a high radiochemical yield (99.3 ± 1.1%) and good stability (>48 h). The radiolabeled nanoemulsion showed an average droplet size of 24.7 nm, a polydispersity index of 0.21, a zeta potential of -45.3 mV, pH 7.4, an osmolality of 285.3 mOsm/kg, and viscosity of 1.24 mPa.s, indicating suitability for parenteral administration. In silico assessment suggested that the labeling did not affect the biological activity of gliclazide. The suggestion was further supported by the in vivo blocking study. Following intravenous administration of nanoemulsion, the pancreas uptake was highest in normal rats (19.57 ± 1.16 and 12 ± 0.13% ID) compared to diabetic rats (8.51 ± 0.16 and 5 ± 0.13% ID) at 1 and 4 h post-injection, respectively. All results supported the feasibility of radioiodinated gliclazide nanoemulsion as a tracer for pancreatic β-cells.

Background: The erector spinae plane block is a new regional anesthetic technique that is gaining popularity in pediatric medicine., Objectives: This study aimed to evaluate the safety and efficacy of ultrasound-guided erector spinae block and compare its analgesic effect with that of the ultrasound-guided caudal block in pediatric patients., Study Design: Prospective, randomized, double-blind, controlled study., Setting: Department of Anesthesia and Intensive Care, faculty of medicine, Minia University, Egypt., Methods: Sixty-three children scheduled for unilateral lower abdominal surgeries, under general anesthesia were randomly allocated into 3 parallel equal groups: Group I (erector spinae block [ESB] group) received ultrasound-guided an erector spinae muscle block in a dose of 0.4 mg/kg of 0.25% bupivacaine between the 10th transverse process and the erector spinae muscles. Group II (caudal block [CB] group) received an ultrasound-guided caudal block in a dose of 2.5 mg/kg of 0.25% bupivacaine. The last group, Group III (control [C] group), did not receive any regional block. Our primary outcome was to evaluate the quality of postoperative analgesia using the Face, Legs, Activity, Cry, Consolability (FLACC) Pain Scale; secondary outcomes were to assess the time to first analgesic request, total analgesic requests during the first 24 hours, and the occurrence of any side effects., Results: The early postoperative FLACC score was less in the ESB group than the CB group; both were lower than the control group. The erector spinae block had a longer duration of analgesia than the caudal block as the median (interquartile range [IQR]) ``of the duration of analgesia in the ESB group was 8 (8-12) hours while it was 6 (6-8) hours in group the CB group; both groups had a longer duration of analgesia compared to the C group 0.25 (0.17-4) hours. The total amount of analgesia was less in the ESB group than the CB group. The number of patients who needed rescue intravenous fentanyl analgesia was 14 patients in the C group while no patient needed intravenous fentanyl in the ESB and CB groups., Limitations: Sensory evaluation of the patients was not done since the 2 blocks were done under general anesthesia but did not affect the outcome., Conclusions: Ultrasound-guided erector spinae block was safe and effective in pediatric patients undergoing unilateral lower abdominal surgery as it provided a longer duration of analgesia and less analgesic requirement than caudal block and fewer side effects.

Avanafil, a selective second-generation phosphodiesterase-5 inhibitor, was successfully labeled with iodine-125 via electrophilic and different factors affecting the labeling efficiency were studied. The labeled compound exhibited in-vitro stability of more than 24 h with a maximum labeling yield of up to 98.4 ± 1.9 %. Molecular modeling and in-vitro assessment of tracer inhibitory activity were performed to ensure that radiolabeling did not affect its binding ability to the target. Biodistribution studies were performed in normal rats and models of erectile dysfunction. The tracer specifically accumulated in the penis, and the clearance appeared to take place via the hepatobiliary route. Results suggested the usefulness of radiolabeled avanafil as a promising tracer for erectile dysfunction., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Lung cancer is characterized by poor prognosis, and is considered a serious disease that causes a significant mortality. The available conventional chemotherapeutic agents suffer from several limitations; hence, new drug molecules are constantly being sought. In the current study, lipid nanovesicles (LNVs) were selected as a colloidal vehicle for encapsulation of the FDA-approved drug; rolapitant (RP), which is used particularly for the treatment of nausea and vomiting, but is repurposed for the treatment of lung cancer in the current work. RP was loaded into various LNVs (liposomes, ethosomes and transethosomes) using the thin film hydration method, and the LNVs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), storage stability and surface morphology. Besides, the in-vitro drug release, in-vitro cytotoxicity on A549 lung cancer cells, nebulization performance using next generation impactor (NGI), and the in-vivo biodistribution behavior were evaluated. The selected ethosomal and transethosomal vesicles displayed a particle size less than 400 nm, a positive charge, and EE% exceeding 90% for RP, with a sustained release pattern over 15 days. The in-vivo biodistribution results proved the high lung deposition potential of RP-LNVs with a considerable safety. Besides, the developed RP-LNVs were able to reach the metastatic organs of lung cancer, hence they were proven promising as a possible treatment modality for lung cancer., (Copyright © 2022. Published by Elsevier B.V.)

This work focuses on tracking ulcerative colitis in mice. High labeling yield and radiochemical purity were achieved for the formation of a [ 125/131 I]balsalazide radiotracer at optimum conditions of oxidizing agent content (chloramines-T [Ch-T], 75 μg), substrate amount (100 μg), pH of reaction mixture (6), reaction time (30 min), and temperature (37°C), using radioactive iodine-125 (200-450 MBq). The radiolabeled compound, [ 125/131 I]balsalazide, was stable in serum and saline solution during 24 h. Balsalazide is acting as a peroxisome proliferator-activated receptor (PPARγ). Biodistribution studies were carried in normal and ulcerated colon mice. High uptake of 75 ± 1.90% injected dose/g organ (ID/g) observed in ulcerated mice confirmed the suitability of [ 131 I]balsalazide as a novel radiotracer for ulcerative colitis imaging in mice., (© 2022 John Wiley & Sons, Ltd.)

Objective: Clonazepam (CP) is a potent long-acting nitrobenzodiazepine derivative that could be used for targeting peripheral benzodiazepine receptors. Phospholipid magnesome is a new vesicular nanosystem recently developed for brain targeting. Improving the uptake of 131 I-CP to the brain might be effective for the diagnosis and/or radiotherapy of certain brain diseases and/or tumors., Methods: CP was radiolabeled with 131 I using direct electrophilic substitution reaction. Quality control of 131 I-CP was performed using different techniques. Different formulas of 131 I-CP were prepared and characterized according to particle size and polydispersity index. The structural features of the optimized formula were then interpreted using transmission electron microscopy and scanning electron microscopy, whereas pharmacokinetic and in vivo behaviors were estimated using the intravenous and intranasal delivery routes., Results: The heart and blood demonstrated lower uptake of 131 I-CP, which inevitably decreased the nontarget effects of radioiodine. Intranasally administered 131 I-CP-loaded magnesomes (INMg) had noticeably higher brain uptake (7.1 ± 0.09%ID/g) with rapid onset of action within 5 min and effective pharmacokinetic behavior. INMg had a drug targeting efficiency and nose-to-brain direct transport percentage of 121.1% and 94.6%, respectively as well as a relative bioavailability of 441.04 ± 75.5%., Conclusion: The present study showed that 131 I-CP-loaded magnesomes can be a beneficial brain-targeting approach for improving the diagnosis and/or radiotherapy of certain brain diseases., (Copyright © 2021. Published by Elsevier B.V.)

Recently, pyrrolizine derivatives have been reported to possess numerous anticancer activities. In a previous study, (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine carboxamide (EZPCA) compound was synthesized and the cytotoxic activity of EZPCA toward COX-2 enzyme (overexpressed in cancer cells) was reported. In order to assess the suitability of this compound as a promising pilot structure for in vivo applications, EZPCA was radiolabeled with radioiodine-131 ( 131 I) and various factors affecting radiolabeling process were studied. Quality control studies of [ 131 I]iodo-EZPCA were performed using paper chromatography and HPLC was used as a co-chromatographic technique for confirming the radiochemical yield. Biodistribution studies of [ 131 I]iodo-EZPCA were undertaken in normal and tumor bearing mice. The radiochemical yield percentage of [ 131 I]iodo-EZPCA was 94.20 ± 0.12%. The biodistribution results showed evident tumor uptake of [ 131 I]iodo-EZPCA with promising target/non-target (T/NT) ratios. As a conclusion, these data suggest that [ 131 I]iodo-EZPCA had high binding efficiency, high tumor uptake and sufficient stability to be used be used in diagnostic studies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The development of cancer theranostic nanomedicines is recommended to concurrently achieve and evaluate the therapeutic benefit and progress. The current work aims to develop gallic acid-gold nanoparticles (GA-Au NPs) as a theranostic probe for 99m Tc-Doxorubicin ( 99m Tc-DOX) based on the spatiotemporal release pattern induced intra-tumoral (IT) delivery. DOX-loaded GA-Au NPs were developed and identified via UV-Vis spectroscopy. The system was characterized for drug loading efficiency%, particle size, zeta potential, topography, in vitro DOX release and anti-proliferative activity against the MCF-7 cell-line. The factors influencing radiolabeling efficiency of DOX with 99m Tc (DOX concentration, stannous chloride concentration, reaction time and pH) were optimized. The in vitro stability in mice serum and in vivo distribution studies in mice of 99m Tc-DOX-loaded GA-Au NPs were investigated following IV and IT administration. Dox-loaded GA-Au NPs had a loading efficiency of 91%, a small particle size (≈50 nm), a promising zeta potential (-20 mV) and a sustained drug release profile at pH 5.3. GA-Au NPs exhibited increased anti-proliferative activity, with approximately a four-fold lower IC 50 value (0.15 μg/ml) than free DOX. The optimized radiolabeling efficiency of 99m Tc-DOX was ≈93%. It showed good physiological stability in mice serum for at least 8 h. The IT delivery of 99m Tc-DOX-loaded GA-Au NPs in tumor-induced mice showed dramatic tumor accumulation. A maximum magnitude of 86.73%ID/g was achieved, at 15 min post-injection, with a target/non-target ratio of ≈56. 99m Tc-DOX-loaded GA-Au NPs could be used for the selective IT delivery of a chemotherapeutic agent and an imaging agent to a target organ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Reaction to sutures is a rare cause of non-healing in clean wounds. Cases of severe reaction to silk sutures have been reported, causing chronic infection and failure of thyroidectomy wound healing. We report a case of retained polyglactin 910 suture presenting with a chronically discharging sinus of the neck after sub-total thyroidectomy., Case: The patient, a 37-year old female, presented with a simple benign multinodular goitre. She had subtotal thyroidectomy and was discharged on day six postoperatively, after satisfactory primary wound healing. The patient observed swelling, pus/discharge and extrusion of the suture in the neck three weeks after surgery. Discharge did not stop after initial wound debridement under local anaesthesia. Computed tomography (CT) scan showed a small area of ring-enhancement soft tissue density, anterior to the right thyroid remnant. Subsequent wound exploration under general anaesthesia revealed a sinus tract extending to the thyroid bed with undegraded strands of thickened polyglactin 910 suture. Suture remnants were removed and the wound healed satisfactorily a week later., Conclusion: Non-healing post thyroidectomy wounds should raise suspicion of a retained suture. Early recognition and surgical intervention will shorten the period of morbidity.

The new thiopyrano[2,3-b]pyridines 4-9 could be synthesized from the nicotinonitrile derivative 1. The cytotoxicity activity of the selected compounds 5, 6 and 8 was tested against MCF-7 and HCT-116 cell lines. The compound 5 (TP5) exhibited significant inhibitory activity and displayed the most potent activity, more than 6 and 8. The compound 5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent. In the light of this result, the labeled 125I-compound 5 (125I-TP5) was prepared and its cytotoxicity against ascites tumor in mice has been evaluated. The results show that compound 5 (TP5) may be potentially used as a radiopharmaceutical for tumor diagnosis when labeled with 125I.

A newly synthesized s-triazine derivative 1,1',1″-(((1,3,5-triazine-2,4,6-triyl) tris (azanediyl)) tris (benzene-4,1-diyl))tris (ethan-1-one), (1), was synthesized as a part of an ongoing research for development of novel s-triazine-based radiopharmaceuticals. In-vitro cell viability assay against different human cancer cell lines showed very promising inhibitory activity of the synthesized compound. This finding encouraged the radioiodination of 1 to study the degree of its localization in tumor site for evaluating the possibility of its use as a tumor imaging agent. The biodistribution study showed good localization of the radioiodinated derivative 2 at tumor site following i.v. administration in solid tumor-bearing mice. Finally, in a trial to understand the mechanism of the anticancer effect exerted by 1, a target prediction study and a docking study were performed. The results of the first study showed that focal adhesion kinase is a possible target for compound 1 and the docking study confirmed successful binding of both compound 1 and its radioiodinated derivative 2 to the binding site of focal adhesion kinase. As a conclusion, the results of this study suggest that, compound 2 could be used as a potential agent for tumor imaging after preclinical trials., (© 2018 John Wiley & Sons, Ltd.)

3-Benzyl-2-((3-methoxybenzyl)thio)benzo[ g ]quinazolin-4(3 H )-one was previously synthesized and proved by physicochemical analyses (HRMS, 1 H and 13 C NMR). The target compound was examined for its radioactivity and the results showed that benzo[ g ]quinazoline was successfully labeled with radioactive iodine using NBS via an electrophilic substitution reaction. The reaction parameters that affected the labeling yield such as concentration, pH and time were studied to optimize the labeling conditions. The radiochemical yield was 91.2 ± 1.22% and the in vitro studies showed that the target compound was stable for up to 24 h. The thyroid was among the other organs in which the uptake of 125 I-benzoquinazoline has increased significantly over the time up to 4.1%. The tumor uptake was 6.95%. Radiochemical and metabolic stability of the benzoquinazoline in vivo/in vitro and biodistribution studies provide some insights about the requirements for developing more potent radiopharmaceutical for targeting the tumor cells.

Background: Recently, the direct intratumoral (i.t.) injection of anticancer agents has been investigated. A newly synthesized Antineoplaston A10 analog 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) showed an antitumor activity in human breast cancer cell line. Unfortunately, MPD suffered from poor water solubility., Materials and Methods: Pseudoternary phase diagram of oil (isopropyl myristate), surfactant (Tween 80), cosurfactant (ethanol), and water was plotted. MPD microemulsion (MPDME) was developed and characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and morphology (transmission electron microscopy). MPDME and MPD solution (MPDS) were radiolabeled with technetium 99m ( 99m Tc) using stannous chloride dihydrate (SnCl 2 .2H 2 O). Molecular docking of MPD and 99m Tc-MPD was performed to study the interaction with DNA., Results: The impacts of intravenous (i.v.) and i.t. injections of 99m Tc-MPDME and 99m Tc-MPDS on biodistribution were studied. The developed MPDME showed spherical droplets with mean PS (74.00 ± 5.69 nm), PDI (0.25 ± 0.03), and ZP (33.90 ± 0.90 mV). Labeling yield of 99m Tc-MPDME and 99m Tc-MPDS was 97.00% ± 0.60% and 92.02% ± 0.45%, respectively. MPD and 99m Tc-MPD showed almost same binding affinity with DNA binding site. Biodistribution results showed that i.t. injection of 99m Tc-MPDME significantly enhanced tumor retention compared to i.v. route., Conclusions: Herein, the authors concluded that microemulsion could be used as i.t. injectable delivery vehicle to improve targeting and tumor retention of MPD.

A10, (3-phenylacetylamino-2,6-piperidinedione), is a natural peptide with broad antineoplastic activity. Recently, in vitro antitumor effect of a new A10 analog [3-(4-methoxybenzoylamino)-2,6-piperidinedione] (MPD) has been verified. However, poor aqueous solubility represents an obstacle towards intravenous formulation of MPD and impedes successful in vivo antitumor activity. To surmount such limitation, MPD microemulsion (MPDME) was developed. A 3 1 2 2 full factorial design using Design-Expert® software was adopted to study the influence of different parameters and select the optimum formulation (MPDME1). Transmission electron microscopy (TEM) displayed spherical droplets of MPDME1. The cytotoxicity of MPDME1 in Michigan Cancer Foundation 7 (MCF-7) breast cancer cell line exceeded that of MPD solution (MPDS) and tamoxifen. Compatibility with injectable diluents, in vitro hemolytic studies and in vivo histopathological examination confirmed the safety of parenteral application of MPDME1. Molecular docking results showed almost same binding affinity of A10, MPD and 125 I-MPD with histone deacetylase 8 (HDAC8) receptor. Accordingly, radioiodination of MPDME1 and MPDS was done via direct electrophilic substitution reaction. Biodistribution of 125 I-MPDME1 and 125 I-MPDS in normal and tumor (ascites and solid) bearing mice showed high accumulation of 125 I-MPDME1 in tumor tissues. Overall, the results proved that MPDME represents promising parenteral delivery system capable of improving antineoplastic activity of MPD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

1,3,5-Triazine-based compounds form a privileged class of compounds in the medicinal chemistry field as they are versatile synthetic scaffolds possessing wide spectra of biological effects including potential anticancer activity. 1,3,5-Triazine compounds explored for anticancer activities have been reported to act by various mechanisms on several molecular targets in human cells such as methyltransferase (DNMT), heat shock protein 90 (Hsp90) and phosphoinositide 3-kinase (PI3K). This review focuses on the synthetic strategies for current developments of 1,3,5-triazine-based anticancer agents and discuses the docking studies that confirm their unique binding modes in the targeted receptors active sites. This article also aims to highlight the future directions for the easy access to these frameworks of more potent and specific anticancer activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objectives: The preparation of 131 I-trazodone hydrochloride and its biological evaluation as a promising brain imaging radiopharmaceutical using two routes of administration., Material and Methods: Trazodone (TZ) was radiolabelled with 131 I using direct electrophilic substitution, and different factors affecting labelling yield were studied. Quality control of 131 I-TZ was carried out using ascending paper chromatography, paper electrophoresis, and high pressure liquid chromatography (HPLC). In vivo biodistribution of 131 I-TZ was evaluated in Swiss albino mice using 3 methods: intravenous 131 I-TZ solution (IVS), intranasal 131 I-TZ solution (INS), and intranasal 131 I-TZ microemulsion (INME)., Results: Optimum labelling yield of 91.23±2.12% was obtained with in vitro stability of 131 I-TZ up to 6h at room temperature. The biodistribution results showed a notably higher and sustained brain uptake for INME compared to IVS and INS at all time intervals. In addition, heart and blood uptake levels for INME were lower than those for IV solution which, in turn, could decrease the systemic side effects of trazodone. Also, the 131 I-trazodone INME brain uptake of 6.7±0.5%ID/g was higher than that of 99m Tc-ECD and 99m Tc-HMPAO (radiopharmaceuticals currently used for brain imaging)., Conclusion: 131/123 I-trazodone formulated as INME could be used as a promising radiopharmaceutical for brain imaging., (Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.)

A novel zoledronic acid (ZL) derivative, 3-(2-ethyl-4-methyi-1H-imidazole-1-yl)-1-hydroxy-1-phosphonopropyl phosphonic acid (EMIHPBP), was synthesized, characterized, and successfully radiolabeled with 99m Tc. The in vivo biodistribution of 99m Tc-EMIHPBP was investigated and compared with the previously reported zoledronate derivatives aiming to formulate a novel zoledronate derivative with a high-potential uptake to bone as a promising antiosteoporotic candidate. To further evaluate the bone uptake efficiency, the pharmacokinetics of 99m Tc-EMIHPBP was investigated and showed that maximum concentration in bone (C max ) was 31.60 ± 0.15%ID/gram after 60 minutes (t max ). Cumulative residence of 99m Tc-EMIHPBP in the bone [AUC (0-∞) (%ID∙min/gram bone)] was 3685.23, mean residence time was 384.354 minutes, and the calculated bone bioavailability was 15.831%. Finally, the time needed for half of the 99m Tc-EMIHPBP formulation to be eliminated from bone (t 1/2 ) was 263.914 minutes. Excellent bone uptake can be obtained 1-hour postinjection with high bone/blood ratio of 23.76 detected with gamma counter. The biodistribution and kinetic studies could recommend EMIHPBP as a promising antiosteoporotic candidate with high selectivity to the skeletal system and rapid clearance from soft tissues., (Copyright © 2017 John Wiley & Sons, Ltd.)

Clomiphene has growth-inhibitory effects of breast cancer cells, clomiphene was successfully labeled with (125)I via direct electrophilic substitution reaction with labeling yield 97%. It was obtained at optimum substrate amount of 0.5mg, Chloramine-T was used as an oxidizing agent at optimum amount of 25µg. Labeling reactions was done at pH 5 at ambient temperature. This study showed good in vitro and in vivo stability of the (125)I-clomiphene. The radiolabeled compound showed high ascetic fluid uptake of 18.12±0.27% at 30min post-injection. Solid tumor uptake of (125)I-clomiphene was 12.48±0.32% at 30min post-injection. This data revealed the localization of tracer in tumor tissue with high percent sufficient to use (125)I-clomiphene as a promising tool for the diagnosis of breast cancer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Ulcerative colitis is a chronic disease having a regressive nature. Commonly used diagnostic methods have the disadvantage to be invasive, time-consuming, and expensive. Therefore, a new sensitive method for the detection and monitoring of disease activity is urgently needed in clinical practice. In the current investigation, radio complexation of olsalazine with technetium-99m, its characterization, and optimization of the labeling conditions were explored. Optimum radiochemical yield of (99m) Tc-olsalazine (97.6% ± 1.8%) was obtained via direct complexation with technetium-99m (~200 MBq) in the presence of stannous chloride dihydrate (100 µg) as reducing agent at pH 6. It was observed that the complex showed significant in vitro stability in serum at 37°C for more than 11 h. The computer-generated optimized geometries of the (99m) Tc-olsalazine were reported, and biodistribution studies were carried out using chemically and microbiologically mice-induced ulcerative colitis models. The tracer showed a good localization in both models and was excreted mainly via liver and to some extent via kidney. Imaging can be performed at 1-2 h post-injection; at that time, the background activity has cleared, and the activity is concentrated in the target site. All the gathered biological data supported the usefulness of (99m) Tc-olsalazine as a potential imaging agent for ulcerative colitis., (Copyright © 2015 John Wiley & Sons, Ltd.)

Compound 2,3-dimethyl-4H-furo[3,2-c]coumarin is a coumarin derivative that could be labeled with 125 I. The process of labeling was started using 1mg of the compound, 50µg CAT oxidizing agent, 30min as reaction time at pH with a yield about 95%. The 125 I-coumarin derivative was stable for about 48h. Radiochemical purity of the labeled compound was performed by electrophoresis and HPLC. The labeled compound was separated with purity about 95%. Tumor transplantation to produce a solid tumor in the right leg of albino mice was made by intramuscular injection of 2×10 6 EAC (Ehrlish acittes carcinoma cells). Biodistribution study of 125 I-coumarin derivative revealed that the uptake in tumor bearing leg was over 5% at 1h and 4h post-injection. This uptake encourages the use of 123 I-coumarin derivative in imaging of tumor sites., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this work was to develop a novel (99m)Tc-labelled derivative based on triphenylethylene for breast cancer imaging. (99m)Tc-Clomiphene was obtained with a radiochemical yield of 94.4% by adding (99m)Tc to 1.5 mg Clomiphene citrate in the presence of 10 μg SnCl(2) at pH 7. The optimization of the labeling yield of Clomiphene citrate, with (99m)Tc, is described. The reaction parameters that affect the labeling yield were studied to optimize the labeling conditions. Radiochemical purity of the final product has been verified by means of paper chromatography and paper electrophoresis. Ehrlich Ascites Carcinoma (EAC) as a model of breast cancer cells was injected intraperitoneally (IP) to produce ascites and intramuscularly (IM) to produce solid tumor. Biodistribution study was carried out by the injecting solution of (99m)Tc-Clomiphene in normal and tumor bearing mice. The uptake in ascites was over 12.5 % injected dose per gram tissue body weight, at 1hr after injection and above 12% in solid tumor. The T/NT value for (99m)Tc-Clomiphene complex was found to be 5.5 ± 0.4 which was higher than that of the commercially available (99m)Tc-MIBI. This data revealed the localization of tracer in tumor tissue with high percent sufficient to use (99m)Tc-Clomiphene as a promising tool for the diagnosis of breast cancer.

Tannic acid is a polyphenolic compound that could be labeled with technetium-99m. To produce about 90% yield of  (99m)Tc-tannic acid in acidic media (pH), the conditions required were 150 μg tin chloride, 30 min reaction time, and 200 μg of the substrate. (99m)Tc-tannic was stable for 6 h. Oral biodistribution of (99m)Tc-tannic showed that it concentrated in the stomach ulcer to reach about 50% of the total injected dose at 1 h after orall administration. This concentration of (99m)Tc-tannic in stomach ulcer may be sufficient to radio-image the presence of ulcer in the stomach.