Evaluation of the potential of annatto seed powder to reduce the formation of heterocyclic amines in charcoal-grilled and pan-fried beef patties.

Various strategies are being explored to reduce the formation of undesirable compounds during the thermal processing of foods. This study investigates the impact of incorporating annatto seed powder (Bixa orellana L.) into beef patties to reduce the formation of heterocyclic amines (HAs) during charcoal-grilling and pan-frying. A three-level full factorial design was used to assess the effect of both annatto seed powder concentration and cooking times on HAs formation. The results showed that HA formation increased with longer cooking times and decreased with higher concentrations of annatto seed powder. A significant reduction in HA content was observed in both charcoal-grilled and pan-fried beef patties when annatto seed powder was added, with a particularly notable 91 % reduction at the 1 % addition level. These findings demonstrate that the addition of annatto seed powder is a highly effective strategy for reducing HA formation in beef patties. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (PubChem CID: 62275); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) (PubChem CID: 104739); 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx) (PubChem CID: 104855); 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (PubChem CID: 1530); 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) (PubChem CID: 5284474); 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) (PubChem CID: 5284476); 2-amino-9H-pyrido[2,3-b]indole (AαC) (PubChem CID: 62805); 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC) (PubChem CID: 62244); Bixin (PubChem CID: 5281226).

Antibacterial and anti-biofilm activities of new fluoroquinolone derivatives coupled with nitrogen-based heterocycles.

We report the design, synthesis, and antimicrobial evaluation of a series of ciprofloxacin (CP) conjugates coupled with nitrogen-containing heterocycles. In vitro screening of these new hybrid compounds (1-13) against a panel of planktonic bacterial strains highlighted thiazolyl homologs 6 and 7 as the most promising candidates for further investigation. These derivatives demonstrated potent growth-inhibitory activity against various standard and clinical isolates, with minimum inhibitory concentrations (MICs) ranging from 0.05 to 0.4 µg/ml, which are higher or comparable to the reference fluoroquinolone. Both compounds effectively inhibited biofilm formation by selected staphylococci across all tested concentrations (1-8 x MIC), displaying greater efficacy at higher doses compared to CP alone. Notably, conjugate 7 also significantly eradicated existing biofilms formed by S. aureus of various origin. Molecular docking studies revealed that conjugate 7 engages in a broader range of interactions with DNA gyrase and DNA topoisomerase IV than CP, suggesting stronger binding affinity and enhanced flexibility. This may contribute to its potential in overcoming bacterial resistance mechanisms. The above findings indicate compound 7 as a promising candidate for clinical development.

One-Pot, Multi-Component Green Microwave-Assisted Synthesis of Bridgehead Bicyclo[4.4.0]boron Heterocycles and DNA Affinity Studies.

Anthranilic acids, salicylaldehydes and arylboronic acids reacted in EtOH/H2O (1/3) at 150 °C under microwave irradiation for 1 h to give, in excellent yields and purity, twenty-three bridgehead bicyclo[4.4.0]boron heterocycles via one-pot, three-component green synthesis. The scope and the limitations of the reactions are discussed in terms of the substitution of ten different anthranilic acids, three salicylaldehydes and three arylboronic acids. The replacement of salicylaldehyde with o-hydroxyacetophenone demanded a lipophilic solvent for the reaction to occur. Eight novel derivatives were isolated following crystallization in a toluene-containing mixture that included molecular sieves. The above one-pot, three-component reactions were completed under microwave irradiation at 180 °C within 1.5 h, thus avoiding the conventional prolonged heating reaction times and the use of a Dean-Stark apparatus. All derivatives were studied for their affinity to calf thymus DNA using proper techniques like viscosity and UV-vis spectroscopy, where DNA-binding constants were found in the range 2.83 × 104-8.41 × 106 M-1. Ethidium bromide replacement studies using fluorescence spectroscopy indicated Stern-Volmer constants between 1.49 × 104 and 5.36 × 104 M-1, whereas the corresponding quenching constants were calculated to be between 6.46 × 1011 and 2.33 × 1012 M-1 s-1. All the above initial experiments show that these compounds may have possible medical applications for DNA-related diseases.

A FAPα-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis.

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients' samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.

The Application of Green Solvents in the Synthesis of S-Heterocyclic Compounds-A Review.

Cyclic organic compounds containing sulfur atoms constitute a large group, and they play an important role in the chemistry of heterocyclic compounds. They are valuable intermediates for the synthesis of other compounds or biologically active compounds themselves. The synthesis of heterocyclic compounds poses a major challenge for organic chemists, especially in the context of applying the principles of "green chemistry". This work is a review of the methods of synthesis of various S-heterocyclic compounds using green solvents such as water, ionic liquids, deep eutectic solvents, glycerol, ethylene glycol, polyethylene glycol, and sabinene. The syntheses of five-, six-, and seven-membered heterocyclic compounds containing a sulfur atom or atoms, as well as those with other heteroatoms and fused-ring systems, are described. It is shown that using green solvents determines the attractiveness of conditions for many reactions; for others, such use constitutes a real compromise between efficiency and mild reaction conditions.

Recent Advances: Heterocycles in Drugs and Drug Discovery.

Interest and research focusing on the design of novel pharmaceutical agents is always growing [...].

Synthesis, Chemical Characterization, and Biological Evaluation of Hydrophilic Gold(I) and Silver(I) N-Heterocyclic Carbenes as Potential Anticancer Agents.

A series of new gold(I) and silver(I) N-heterocyclic carbenes bearing a 1-thio-ß-d-glucose tetraacetate moiety was synthesized and chemically characterized. The compounds' stability and solubility in physiological conditions were investigated employing a multitechnique approach. Interaction studies with biologically relevant proteins, such as superoxide dismutase (SOD) and human serum albumin (HSA), were conducted via UV-vis absorption spectroscopy and high-resolution ESI mass spectrometry. The biological activity of the compounds was evaluated in the A2780 and A2780R (cisplatin-resistant) ovarian cancer cell lines and the HSkMC (human skeletal muscle) healthy cell line. Inhibition studies of the selenoenzyme thioredoxin reductase (TrxR) were also carried out. The results highlighted that the gold complexes are more stable in aqueous environment and capable of interaction with SOD and HSA. Moreover, these carbenes strongly inhibited the TrxR activity. In contrast, the silver ones underwent structural alterations in the aqueous medium and showed greater antiproliferative activity.

Fe3O4@gC3N4@Thiamine: a novel heterogeneous catalyst for the synthesis of heterocyclic compounds and microextraction of tebuconazole in food samples.

Graphite carbon nitride (g-C3N4) is a two-dimensional nano-sheet with electronic properties, which shows unique characteristics with high chemical and thermal stability in its structure. The functionalization of these compounds through covalent bonding is an important step towards significantly improving their properties and capabilities. To achieve this goal, a novel strategy for the covalent functionalization of Fe3O4@g-C3N4 with thiamine hydrochloride (vitamin B1) via cyanuric chloride (TCT), which is a divalent covalent linker, was presented. The efficiency of Fe3O4@gC3N4@Thiamine as a heterogeneous organic catalyst in the synthesis of spirooxindole-pyran derivatives and 2-amino-4H-pyran under solvent-free conditions was evaluated and the yields of high-purity products were presented. In addition, easy recycling and reuse for seven consecutive cycles without significant reduction in catalytic activity are other features of this catalyst. Moreover, the performance of the prepared sorbent in the microextraction technique (herein, magnetic solid phase extraction) was studied. The tebuconazole was selected as the target analyte. The target analyte was extracted and determined by HPLC-UV. Under the optimum condition, the linear range of the method (LDR) was estimated in the range of 0.2-100 µg L-1 (the coefficient of determination of 0.9962 for tebuconazole). The detection limit (LOD) of the method for tebuconazole was calculated to be 0.05 µg L-1. The limit of quantification (LOQ) of the method was also estimated to be 0.16 µg L-1. In order to check the precision of the proposed method, the intra-day and inter-day relative standard deviations (RSD%) were calculated, which were in the range of 1.5- 2.8%. The method was used for the successful extraction and determination of tebuconazole in tomato, cucumber, and carrot samples.

Preemptive Approach to Plerixafor Use Is Optimal in Patients With Relapsed/Refractory Germ Cell Tumors Undergoing Peripheral Blood Hematopoietic Stem Cell Collection: Effect on Collection Days, Yields, and Cost.

Evidence describing the use of plerixafor in the off-label population of relapsed/refractory germ cell tumors (GCT) is limited. We aim to describe the effect of rescue versus preemptive plerixafor use on apheresis collection days, collection yields, and cost. We retrospectively collected data on 77 consecutive patients (at least 15 years of age) with GCT who underwent peripheral blood stem cell (PBSC) collection for autologous stem cell transplant between January 1, 2020 and May 1, 2022. Depending on insurance approval, plerixafor was given either as "rescue" (after a first apheresis collection of < 5 × 106 CD34+ cells/kg) or as "preemptive" on Day 4 of granulocyte-colony stimulating factor (G-CSF) prior to the first apheresis collection, if the Day 4 peripheral blood CD34+ count was < 40 cells/µL. A total of 66% of patients who received preemptive plerixafor completed collection in 1 day, similar to good mobilizers who only needed G-CSF (71%, p = 0.366). In contrast, all poor mobilizers in the rescue group required at least 2 days of collection and had lower CD34+ cell yields than the preemptive group (7.15 vs. 9.81 × 106/kg, p = 0.0055). A cost analysis revealed that preemptive plerixafor may save approximately $7000 per patient compared with a rescue approach. Preemptive plerixafor in GCT patients undergoing PBSC collection allows relatively poor mobilizers to collect in fewer days and with lower overall cost. Fewer apheresis procedures result in less risk to the patient, increased patient satisfaction, and the ability to schedule more patients within the constraints of staffing.

Synthesis and antibacterial activities of heterocyclic ring-fused 20(S)-protopanaxadiol derivatives.

Multidrug-resistant (MDR) bacterial infections are becoming a life-threatening issue in public health; therefore, it is urgent to develop novel antibacterial agents for treating infections caused by MDR bacteria. The 20(S)-protopanaxadiol (PPD) derivative 9 was identified as a novel antibacterial hit compound in screening of our small synthetic natural product-like (NPL) library. A series of novel PPD derivatives with heterocyclic rings fused at the C-2 and C-3 positions of the A-ring were synthesized and their antibacterial activities against Staphylococcus aureus (S. aureus) Newman strain and MDR S. aureus strains (USA300, NRS-1, NRS-70, NRS-100, NRS-108, NRS-271, XJ017, and XJ036) were evaluated. Among these compounds, quinoxaline derivative 56 (SH617) exhibited the highest activity with MICs of 0.5-4 µg/mL against the S. aureus Newman strain and the eight MDR S. aureus strains. Its antibacterial activity was comparable to that of the positive control, vancomycin. In the zebrafish, 56 revealed no obvious toxicity even at a high administered dose. In vivo, following a lethal infection induced by USA300 strains in zebrafish, 56 exhibited significantly increased survival rates in a dose-dependent manner.

Construction of CXCR4 Receptor-Targeted CuFeSe2 Nano Theranostic Platform and Its Application in MR/CT Dual Model Imaging and Photothermal Therapy.

Introduction: Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need. Methods: We introduce an "all-in-one" tumor-targeted theranostic platform using CuFeSe2-based composite nanoparticles (CuFeSe2@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation. Plerixafor (AMD3100) is bonded to the surface of CuFeSe2 as a targeting unit. Due to the robust interaction between AMD3100 and the overexpressed Chemokine CXC type receptor 4 (CXCR4) on the membrane of 4T1 cancer cells, CuFeSe2@PA specifically recognizes 4T1 cancer cells, enriching the tumor region. Results: CuFeSe2@PA serves as a contrast agent for T2-weighted MR imaging (relaxivity value of 1.61 mM-1 s-1) and CT imaging. Moreover, it effectively suppresses tumor growth through photothermal therapy (PTT) owing to its high photothermal conversion capability and stability, with minimized side effects demonstrated both in vitro and in vivo. Discussion: CuFeSe2@PA nanoparticles show potential as dual-mode imaging contrast agents for MR and CT and provide an effective means of tumor treatment through photothermal therapy. The surface modification with Plerixafor enhances the targeting ability of the nanoparticles, performing more significant efficacy and biocompatibility in the 4T1 cancer cell model. The study demonstrates that CuFeSe2@PA is a promising multifunctional theranostic platform with clinical application potential.

Rational Design of Mono-Substituted Gd-DOTA as Highly Stable and Efficient MRI Contrast Agents for Hepatobiliary and Inflammation Imaging.

Hepatobiliary-specific magnetic resonance imaging contrast agents (MRI CAs) play a crucial role in the early diagnosis of hepatocellular carcinoma (HCC). However, only two acyclic CAs, Gd-BOPTA and Gd-EOB-DTPA, exhibit unfavorable kinetic inertness. Our study focused on the development of superior stable innovative macrocyclic CAs. By introducing a lipophilic benzyloxy group (OBn) into the H4DOTA ring (Gd-L1), we achieved significant enhancement in kinetic inertness. In vivo experiments in mice demonstrated that 40% of the dosage was distributed to the liver at 5 min, providing sustained hepatic enhancement for over 35 min. We also developed an MPO-responsive MRI CA (Gd-L3), which can participate in the "peroxidase cycle" as the substrate, generating oligomers with a 3.8-fold increase in relaxivity, and selectively enhance the lesion in an acute gout mouse model. Overall, our work represents a significant advancement in the field of hepatic and inflammatory MRI, offering promising avenues for early diagnosis and improved imaging outcomes.

Selective Tyrosine Kinase 2 (TYK2) Inhibition in Plaque Psoriasis.

Members of the Janus kinase (JAK) superfamily, comprising tyrosine kinase 2 (TYK2) and JAK1, JAK2, and JAK3, mediate signaling by cytokines (eg, interleukin [IL]-23) involved in psoriasis pathogenesis. Binding of IL-23 to its receptor activates TYK2 and JAK2, which trigger signal transducer and activator of transcription (STAT) translocation to the nucleus to regulate target gene transcription, including genes of proinflammatory mediators such as IL-17. Physiologically, TYK2 solely mediates immune function, whereas JAK1,2,3 mediate broad systemic and immune functions. Inhibition of individual JAK family members is being evaluated in many dermatologic indications, including psoriasis. Selective TYK2 inhibition is therefore expected to be associated with few adverse effects in patients with psoriasis. People with genetic mutations leading to loss of function of TYK2 are protected from the development of psoriasis without an increased risk of infections or malignancies. In contrast, treatments with JAK1,2,3 inhibitors are associated with various systemic effects. We review the unique allosteric mechanism of action of the selective TYK2 inhibitor, deucravacitinib, which binds to the TYK2 regulatory (pseudokinase) domain, and the mechanisms of action of JAK1,2,3 inhibitors, which bind to the adenosine 5'-triphosphate-binding active (catalytic) site in the kinase domains of JAK1,2,3. Deucravacitinib, which is approved for the treatment of moderate to severe plaque psoriasis in adults in the United States and several other countries, represents a novel, targeted systemic treatment approach with a favorable safety profile. J Drugs Dermatol. 2024;23(8):645-652.  doi:10.36849/JDD.8293.

Palladium(II)-Indenyl Complexes Bearing N-Heterocyclic Carbene (NHC) Ligands as Potent and Selective Metallodrugs toward High-Grade Serous Ovarian Cancer Models.

In this study, we synthesized novel Pd(II)-indenyl complexes using various N-heterocyclic carbene (NHC) ligands, including chelating NHC-picolyl, NHC-thioether, and diNHC ligands, and two monodentate NHCs. Transmetalation reactions between a Pd(II)-indenyl precursor and silver-NHC complexes were generally employed, except for chelating diNHC derivatives, which required direct reaction with bisimidazolium salts and potassium carbonate. Characterization included NMR, HRMS analysis, and single-crystal X-ray diffraction. In vitro on five ovarian cancer cell lines showed notable cytotoxicity, with IC50 values in the micro- and submicromolar range. Some compounds exhibited intriguing selectivity for cancer cells due to higher tumor cell uptake. Mechanistic studies revealed that monodentate NHCs induced mitochondrial damage while chelating ligands caused DNA damage. One chelating NHC-picolyl ligand showed promising cytotoxicity and selectivity in high-grade serous ovarian cancer models, supporting its consideration for preclinical study.

Influence of Some Heterocyclic, Cyclic, and Nitrogen-Containing Compounds on Oxidative Deamination of Polyamines in a Cell-Free Test System.

We studied the effects of some nitrogen-containing, heterocyclic, and cyclic compounds on the rate of oxidative deamination of polyamines and putrescine in tissues with a high proliferation rate. For this purpose, the specific activities of the main enzymes of polyamine oxidative degradation - spermine oxidase (SMO), polyamine oxidase (PAO), and diamine oxidase (DAO) were determined using a cell-free test system from regenerating rat liver. The compounds methyl 2-(5-formylfuran-2-yl)benzoate and 2,7-bis-[2-(diethylamino)ethoxy]-9H-fluoren-9-one (and in the form of dihydrochloride) showed mainly activating effect on oxidative degradation of putrescine, spermidine, and spermine, which indirectly indicates their antiproliferative effect. Nitrogen-free compounds inhibited this process, thus exhibiting potentially carcinogenic properties. Correlations were calculated for activity of DAO, PAO, and SMO with 5 topological indices: Wiener (W), Rouvray (R), Balaban (J) in the Trinaistich modification, detour (Ip), and electropy (Ie). The highest dependence was noted for DAO and the Balaban index (R=-0.55), for PAO and the detour index (R=0.78), and for SMO and the electropy index (R=0.53). The remaining dependencies showed insignificant correlation strength.

A magnetic carboxyl-functionalized covalent organic framework for the efficient enrichment of foodborne heterocyclic aromatic amines prior to UPLC-MS analysis.

Foodborne heterocyclic aromatic amines (HAAs) are potent mutagens and carcinogens, posing significant health risks. Existing enrichment methods for HAAs need better adsorption selectivity and capacity for daily exposure assessment. This study hypothesized that introducing carboxylic groups into magnetic covalent organic frameworks (m-COFs) would improve HAAs adsorption by providing additional binding sites. Hence, we prepared a novel magnetic adsorbent, termed as Fe3O4@DOPA-TpPa-(COOH)2 capable of enhancing the HAAs detection through magnetic solid-phase extraction (MSPE) coupled with UPLC-MS. This sorbent demonstrated a large specific surface area (130.7 m2/g), high magnetic responsivity (21.05 emu/g), and robust stability, with an adsorption capacity (Qm[cal]: 81.82 mg/g) driven by electrostatic, LP - π/C-H - π interactions, and hydrogen bonding. Optimal MSPE conditions provided sensitive detection with a broad linear range (5-500 ng/mL), low limits of detection (0.01-7.01 ng/g), and excellent repeatability. Application to Cantonese mooncake samples showed satisfactory recoveries (62.12%-126.86%). This method offers a more accurate tool for detecting HAAs.

Investigation of 2,4-Dihydroxylaryl-Substituted Heterocycles as Inhibitors of the Growth and Development of Biotrophic Fungal Pathogens Associated with the Most Common Cereal Diseases.

Climate change forces agriculture to face the rapidly growing virulence of biotrophic fungal pathogens, which in turn drives researchers to seek new ways of combatting or limiting the spread of diseases caused by the same. While the use of agrochemicals may be the most efficient strategy in this context, it is important to ensure that such chemicals are safe for the natural environment. Heterocyclic compounds have enormous biological potential. A series of heterocyclic scaffolds (1,3,4-thiadiazole, 1,3-thiazole, 1,2,4-triazole, benzothiazine, benzothiadiazine, and quinazoline) containing 2,4-dihydroxylaryl substituents were investigated for their ability to inhibit the growth and development of biotrophic fungal pathogens associated with several important cereal diseases. Of the 33 analysed compounds, 3 were identified as having high inhibitory potential against Blumeria and Puccinia fungi. The conducted research indicated that the analysed compounds can be used to reduce the incidence of fungal diseases in cereals; however, further thorough research is required to investigate their effects on plant-pathogen systems, including molecular studies to determine the exact mechanism of their activity.

Biological Evaluation of Dinuclear Platinum(II) Complexes with Aromatic N-Heterocycles as Bridging Ligands.

The history of effective anti-cancer medications begins with the discovery of cisplatin's anti-cancer properties. Second-generation analogue, carboplatin, with a similar range of effectiveness, made progress in improving these drugs with fewer side effects and better solubility. Renewed interest in platinum-based drugs has been increasing in the past several years. These developments highlight a revitalized enthusiasm and ongoing exploration in platinum chemotherapy based on the series of dinuclear platinum(II) complexes, [{Pt(L)Cl}2(µ-bridging ligand)]2+, which have been synthesized and evaluated for their biological activities. These complexes are designed to target various cancerous conditions, exhibiting promising antitumor, antiproliferative, and apoptosis-inducing activities. The current work aims to shed light on the potential of these complexes as next-generation platinum-based therapies, highlighting their enhanced efficacy and reduced side effects, which could revolutionize the approach to chemotherapy.

First Biodistribution Study of [68Ga]Ga-NOTA-Insulin Following Intranasal Administration in Adult Vervet Monkeys.

Background: Intranasal insulin (INI) is being explored as a treatment for Alzheimer's disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes. Objective: To show reliable delivery of insulin to the brain using the Aptar Cartridge Pump System (CPS) intranasal delivery system. Methods: To visualize INI biodistribution, we developed a novel PET radiotracer, Gallium 68-radiolabeled (NOTA-conjugated) insulin, [68Ga]Ga-NOTA-insulin. We used the Aptar CPS to administer [68Ga]Ga-NOTA-insulin to anesthetized healthy adult vervet monkeys and measured brain regional activity and whole-body dosimetry following PET/CT scans. Results: We observed brain penetration of [68Ga]Ga-NOTA-insulin following intranasal administration with the Aptar CPS. Radioactive uptake was seen in multiple regions, including the amygdala, putamen, hypothalamus, hippocampus, and choroid plexus. A safety profile and whole-body dosimetry were also established in a second cohort of vervets. Safety was confirmed: vitals remained stable, blood glucose levels were unchanged, and no organ was exposed to more than 2.5 mSv of radioactivity. Extrapolations from vervet organ distribution allowed for estimation of the [68Ga]Ga-NOTA-insulin absorbed dose in humans, and the maximum dose of [68Ga]Ga-NOTA-insulin that can be safely administered to humans was determined to be 185 MBq. Conclusions: The use of [68Ga]Ga-NOTA-insulin as a PET radiotracer is safe and effective for observing brain uptake in vervet monkeys. Further, the Aptar CPS successfully targets [68Ga]Ga-NOTA-insulin to the brain. The data will be essential in guiding future studies of intranasal [68Ga]Ga-NOTA-insulin administration in humans.

Investigation on synergistic inhibition of protein-bound heterocyclic amines in sarcoplasmic and myofibrillar model systems by amino acid combinations.

The inhibition of amino acids on the formation of protein-bound HAs was assessed in both model systems and roast beef patties, and the synergism between these amino acids was also investigated. The amino acids can promote the formation of protein-bound HAs at low addition amount, and the total content of protein-bound HAs increased from 444.05 ± 4.98 ng/g of the control group to 517.36 ± 16.51 ng/g when 0.05 % cysteine was added. Amino acid combinations exhibited stable inhibitory effects, with the maximum inhibitory rate of 64 % in the treatment with histidine-proline combination (1:4). The synergistic inhibition may be caused by simultaneously scavenging intermediates and competing for the binding sites of muscle proteins, and the reaction with protein-bound HAs to form adduct can serve as supporting factors to co-mitigate the promotion in protein-bound HAs from increased protein solubility. These findings proposed the potential mitigation strategies against protein-bound HAs formation.