Biologists have significantly improved various techniques for confirming the physiological and pharmacological activity of new proteins produced by recombinant DNA technology, such as Western blotting, ELISA, and flow cytometry. Although these methods are costly and comparatively low in efficiency, our study focuses on developing a real-time approach to investigate the physiological activity of our new recombinant human insulin (rh-Insulin), which is expressed in Escherichia coli. An in vivo biodistribution study of radioiodinated rh-Insulin (125I-rh-Insulin) was conducted in diabetic-induced mice, exploiting the capability of tyrosine residues in protein molecules to undergo electrophilic substitution of hydrogen atoms with traceable 125I atoms. We studied many factors to optimize the conditions for the iodination reaction, including the amount of substrate, the amount of chloramine-T, pH, temperature, and reaction time. A high radiochemical yield of 99.01 ± 0.2% was achieved. The in vivo step involved the administration of 125I-rh-Insulin intravenously (I.V.) in previously induced diabetic mice to study the pharmacokinetics of the new insulin analog. Results show a homogeneous distribution of insulin molecules throughout the body organs, correlating with organ mass, size, and functionality, with no accumulation in distinct organs. The clearance of insulin from the body occurs via both renal and hepatic routes due to the aqueous nature of insulin. Additionally, a parallel experiment was conducted on diabetic mice using only rh-Insulin, resulting in a significant reduction in glucose levels in the mice's blood, thereby exploring the physiological activity of insulin and confirming the ability of our new construct to lower blood glucose levels in diabetic mice. Consequently, this method appears to be much more rapid and effective for the evaluation of biological molecules in vivo using radioactive tracing techniques.

Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA. Four derivatives 3b, 3c, 3d and 3e elicited remarkable GI% against MDA-MB-468, T-47D and MCF-7 breast cancer cell lines. Thereafter, MTT assay was performed to reveal that compounds 3b (IC50 = 2.27 µM) and 3d (IC50 = 1.46 µM) showed promising cytotoxic activity against MCF-7 and MDA-MB-468 cell lines, respectively, compared to their reference drugs. Compounds 3b, 3d and 3e revealed good selectivity toward tumor cells with reasonable safety profile when tested against the normal cell line MCF-10a. In vitro EGFR inhibitory assay demonstrated that compounds 3b (IC50 = 0.099 µM) and 3d (IC50 = 0.086 µM) exhibited comparable inhibitory activity to the standard drug erlotinib (IC50 = 0.046 µM). A flow cytometric analysis demonstrated that derivatives 3b and 3d arrested the cell cycle at the S phase in MCF-7 and MDB-MB-468, respectively. Furthermore, the most active derivative 3d was subjected to in vivo radioactive studies. In-vivo biodistribution of 99mTc-3d complex showed a notable elevated accumulation in the targeted sarcoma muscle, indicating the targeting capacity of compound 3d in the tumor of sarcoma mice model. The binding mode of compounds 3b and 3d with EGFR was studied by molecular docking and was further inspected by molecular dynamic simulations. Both compounds were shown to be stable during the course of simulation and demonstrated a plausible interaction pattern with the EGFR binding pocket.

Oxidative stress is a key factor in the pathological processes that trigger various chronic liver diseases, and significantly contributes to the development of hepatocarcinogenesis. Natural antioxidants reduce oxidative stress by neutralizing free radicals and play a crucial role in the treatment of free-radical-induced liver diseases. However, their efficacy is often limited by poor bioavailability and metabolic stability. To address these limitations, recent advances have focused on developing nano-drug delivery systems that protect them from degradation and enhance their therapeutic potential. Among the several critical benefits, they showed to be able to improve bioavailability and targeted delivery, thereby reducing off-target effects by specifically directing the antioxidant to the liver tumor site. Moreover, these nanosystems led to sustained release, prolonging the therapeutic effect over time. Some of them also exhibited synergistic effects when combined with other therapeutic agents, allowing for improved overall efficacy. This review aims to discuss recent scientific advances in nano-formulations containing natural antioxidant molecules, highlighting their potential as promising therapeutic approaches for the treatment of liver cancer. The novelty of this review lies in its comprehensive focus on the latest developments in nano-formulations of natural antioxidants for the treatment of liver cancer.

Liver disorders are one of the most common pathological problems worldwide. It affects more than 1.5 billion worldwide. Many types of hepatic cells have been reported to be involved in the initiation and propagation of both acute and chronic liver diseases, including hepatocytes, Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells (HSCs). In addition, oxidative stress, cytokines, fibrogenic factors, microRNAs, and autophagy are also involved. Understanding the molecular mechanisms of liver diseases leads to discovering new therapeutic interventions that can be used in clinics. Recently, antioxidant, anti-inflammatory, anti-HSCs therapy, gene therapy, cell therapy, gut microbiota, and nanoparticles have great potential for preventing and treating liver diseases. Here, we explored the recent possible molecular mechanisms involved in the pathogenesis of acute and chronic liver diseases. Besides, we overviewed the recent therapeutic interventions that targeted liver diseases and summarized the recent studies concerning liver disorders therapy.

New pyrazolone derivatives were successfully synthesized by both microwave-assisted and conventional techniques. Compound 3 (3-(3-Methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)-3-oxopropanehydrazide) displayed remarkable anti-cancer activity (IC50 obtained at 8.71 and 10.63 µM for HCT-116 and MCF-7, respectively. Moreover, biodistribution study using radiolabeling approach revealed a remarked uptake of [99mTc]Tc-compound 3 complex into tumour induced in mice. The biodistribution showed high accumulation in tumour tissues with T/NT of 6.92 after 60 min post injection. As a result of these promising data, the newly synthesized compounds especially compound 3 affords a potential radio-carrier that could be used as a tumour marker and can be used for cancer therapy after further preclinical studies.

This study aims to investigate the bioproduction and prospective biological applications of a natural red pigment from Talaromyces purpureogenus AUMC2603. Maximum pigment yield was achieved by a numerical optimization at pH 6, temperature 25°C, and an 18-day incubation period on Yeast Malt Broth (YMB) media. The crude pigment was separated and purified into two pigment fractions via solid-phase extraction and then characterized as anthraquinone (dominant) and herquinone by LC/MS and ¹HNMR analysis. The crude pigment extract and the two separated fractions displayed a potential antioxidant activity. Additionally, they showed a powerful anticancer activity towards cancer cell lines, MCF-7, HepG-2, and HCT116 with less cytotoxicity on normal cell lines, MCF12F and BJ-1T. The radioiodination efficiency of the radiosynthesized ^99mTc-anthraquinone pigment complex was also investigated and optimized, obtaining a radiochemical yield of 92.70% ± 0.89%. An in vivo biodistribution study of the ^99mTc-anthraquinone pigment complex demonstrated a high kidney uptake of 34% injected dose per gram of organ tissue 60min after intravenous injection, and the complex retention remained high up to 120min. The current study is the first bioassay report on the efficacy of a purified anthraquinone from T. purpureogenus as a potent agent for kidney radio-imaging that could be applied in kidney cancer diagnosis.

Background: Zoledronate suppresses human sarcomas by blocking the formation of geranylgeranyl diphosphate (GGPP) via inhibiting GGPP synthase.Objectives: Designing of new derivative of dronic acid (1-hydroxy-2-(4-nitro-1H-imidazol-1-yl)ethan-1,1-diyl)bis phosphonic acid), structurally related to zoledronate to be used for osteosarcoma therapy.Methods: 1-hydroxy-2-(4-nitro-1H-imidazol-1-yl)ethan-1,1-diyl)bis(phosphonic acid) was synthesized in one pot reaction with a yield of 65 ± 4%. The synthesized nitro-zoledronate compound was successfully radiolabeled with 99mTc with a radiochemical purity of 92.05%. Docking accuracy and scoring reliability for the new nitro-zoledronate with human GGPPS using MOE software has been presented.Results and Conclusion: The nitro-zoledronate successfully coupled with technetium-99m at high yield to investigate its in-vivo biodistribution which indicated highly selective uptake in the skeletal system and rapid clearance from soft tissues. The in-vitro cytotoxicity of the nitro-zoledronate was evaluated and potently inhibited the osteosarcoma cell line (MG-63) after 72 hours with an IC50 value of 10 μM. To summarize, our data point to a promising candidate to improve osteosarcoma therapy.

Overall, 12% of the global population (800 million) suffers from liver disease, which causes 2 million deaths every year. Liver injury involving characteristic reactive oxygen/nitrogen species (RONS) and inflammation plays a key role in progression of liver disease. As a key metabolic organ of the human body, the liver is susceptible to injury from various sources, including COVID-19 infection. Owing to unique structural features and functions of the liver, most current antioxidants and anti-inflammatory drugs are limited against liver injury. However, the characteristics of the liver could be utilized in the development of nanodrugs to achieve specific enrichment in the liver and consequently targeted treatment. Nanodrugs have shown significant potential in eliminating RONS and regulating inflammation, presenting an attractive therapeutic tool for liver disease through controlling liver injury. Therefore, the main aim of the current review is to provide a comprehensive summary of the latest developments contributing to our understanding of the mechanisms underlying nanodrugs in the treatment of liver injury via harnessing RONS and inflammation. Meanwhile, the prospects of nanodrugs for liver injury therapy are systematically discussed, which provides a sound platform for novel therapeutic insights and inspiration for design of nanodrugs to treat liver disease.