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Despite the great advances in discovering cyclic peptides against protein targets, their reduced aqueous solubility, cell permeability, and activity of the cyclic peptide restrict its utilization in advanced biological research and therapeutic applications. Here we report on a novel approach of structural alternation of the exocyclic and linker parts that led to a new derivative with significantly improved cell activity allowing us to dissect its mode of action in detail. We have identified an effective cyclic peptide (CP7) that induces approximately a 9-fold increase in DNA damage accumulation and a remarkable increase in apoptotic cancer cell death compared to the reported molecule. Notably, treating cells with CP7 leads to a dramatic decrease in the efficiency of non-homologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs), which is accompanied by an increase in homologous recombination (HR) repair. Interestingly, treating BRCA1-deficient cells with CP7 restores HR integrity, which is accompanied by increased resistance to CP7. Additionally, CP7 treatment increases the sensitivity of cancer cells to ionizing radiation. Collectively, our findings demonstrate that CP7 is a selective inhibitor of NHEJ, offering a potential strategy to enhance the effectiveness of radiation therapy., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: The aim of this study was to evaluate the effect of the use of different NaOCl concentrations (1%, 2.5%, and 5.25%) during root canal treatment of molar teeth with symptomatic irreversible pulpitis on the change of the IL-8 level in gingival crevicular fluid (GFC)., Methods: GCF sampling was performed on experimental tooth with irreversible pulpitis before and after treatment and also contralateral healthy tooth of 54 patients. The patients were divided into three groups according to concentration of NaOCl solution (n = 18); 1%, 2.5%, and 5.25% NaOCl solution. GCF sampling from experimental teeth was repeated one week after root canal treatment. Statistical analysis was performed using Mann-Whitney U, Wilcoxon test, one-way ANOVA and Pearson correlation analysis., Results: There was a significant correlation between IL-8 levels in GCF samples taken from teeth with pulpitis before treatment and from healthy contralateral teeth (p = .000). Furthermore, the pretreatment IL-8 level was significantly higher than the posttreatment IL-8 level(p < .05). The effect of the NaOCl concentration on the change in IL-8 level betweeen pre and post treatment was not found statistically significant (p > .05)., Conclusions: The use of NaOCl during root canal treatment can effectively reduce the levels of IL-8 in GCF and improve clinical outcomes., Trial Registration: This study was registred in the Institutional Review Board and the Ethics Committee of the University (No:11) on 15/12/2021., (© 2024. The Author(s).)

α-Conotoxins are well-known probes for the characterization of the various subtypes of nicotinic acetylcholine receptors (nAChRs). Identifying new α-conotoxins with different pharmacological profiles can provide further insights into the physiological or pathological roles of the numerous nAChR isoforms found at the neuromuscular junction, the central and peripheral nervous systems, and other cells such as immune cells. This study focuses on the synthesis and characterization of two novel α-conotoxins obtained from two species endemic to the Marquesas Islands, namely Conus gauguini and Conus adamsonii . Both species prey on fish, and their venom is considered a rich source of bioactive peptides that can target a wide range of pharmacological receptors in vertebrates. Here, we demonstrate the versatile use of a one-pot disulfide bond synthesis to achieve the α-conotoxin fold [Cys 1-3; 2-4] for GaIA and AdIA, using the 2-nitrobenzyl (NBzl) protecting group of cysteines for effective regioselective oxidation. The potency and selectivity of GaIA and AdIA against rat nicotinic acetylcholine receptors were investigated electrophysiologically and revealed potent inhibitory activities. GaIA was most active at the muscle nAChR (IC 50 = 38 nM), whereas AdIA was most potent at the neuronal α6/3 β2β3 subtype (IC 50 = 177 nM). Overall, this study contributes to a better understanding of the structure-activity relationships of α-conotoxins, which may help in the design of more selective tools.

Background: The purpose of this study was to assess the push-out bond strength of calcium-silicate and silicone based root canal sealers in bulk and with main cone., Methods: Roots (n=48) randomly divided into 4 groups (n=12) according to the obturation protocol; (1) iRoot SP in bulk; (2) iRoot SP with gutta-percha; (3) GuttaFlow Bioseal in bulk; (4) GuttaFlow Bioseal with gutta-percha. Six horizontal sections were obtained from each root (n=72). Effect of sealers on bond strength was statistically significant ( P <0.05)., Results: Highest mean value was obtained in iRoot-Bulk group and lowest in GuttaFlow Bioseal-GP group. Both iRoot SP groups had significantly higher bond strength values than both GuttaFlow Bioseal groups ( P <0.05). There was no significant difference between iRoot-GP and iRoot-Bulk groups ( P =0.603) also GuttaFlow Bioseal-GP and GuttaFlow Bioseal-Bulk groups ( P =0.684)., Conclusion: Based on findings, using calcium silicate-based sealer in bulk can be also suitable in clinical practice., Competing Interests: The authors declared that they have no conflicts of interest related to this study., (©2022 The Author(s).)

Microbial ecosystem consists of a complex community of bacterial interactions and its host microenvironment (tissue, cell, metabolite). Because the interaction between gut microbiota and host involves many diseases and seriously affects human health, the study of the interaction mechanism between gut microbiota and host has attracted great attention. The gut microbiome is made up of 100 trillion bacteria that have both beneficial and adverse effects on human health. The development of IgA Nephropathy results in changes in the intestinal microbial ecosystem that affect host physiology and health. Similarly, changes in intestinal microbiota also affect the development of IgA Nephropathy. Thus, the gut microbiome represents a novel therapeutic target for improving the outcome of IgA Nephropathy, including hematuria symptoms and disease progression. In this review, we summarize the effect of intestinal microbiota on IgA Nephropathy in recent years and it has been clarified that the intestinal microbiota has a great influence on the pathogenesis and treatment of IgA Nephropathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Tian, Sun, Zhou, Zhi, Qing, Abdi Saed, Dong, Zhang and Li.)

In this brief report, we reported an IgA nephropathy (IgAN) patient who presented in November 2020 with an acute exacerbation with massive proteinuria and diarrhea. He had the earliest onset in 2018 when his IgAN was diagnosed by renal biopsy. He has been treated with active ACEI/ARB drugs for more than 90 days, intermittent steroid therapy, combined with anti-infective therapy. Although his acute symptoms resolved with each episode, he became increasingly severe as the interval between episodes shortened. Accordingly, the immunosuppressive drugs were administered under the KDIGO guidelines and related guidelines. However, the patient and his family refused this treatment. We pondered over the possible pathogenesis of IgAN, and after a full discussion with the patient and his family, FMT was administered to him after obtaining his informed consent. During the FMT procedure, one healthy volunteer (the doctor himself) also took the FMT capsules. In the end, the patient's urine protein dropped significantly and even turned negative after treatment. Neither the patient nor the healthy volunteer experienced any serious adverse effects during the use of the capsules and the subsequent 6-month follow-up period. We also used metagenomic sequencing to analyze the intestinal flora of patients before and after treatment, and a gradual increase stood out in the abundance of the patient's intestinal flora after drug administration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhi, Song, Abdi Saed, Wang and Li.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.