Current Medicinal Chemistry - Volume 30, Issue 33, 2023

We are experiencing a revolution in regenerative medicine. Recent developments in organoid technology have provided unique opportunities for studying human biology and diseases. Indeed, organoid models have revolutionized the in vitro culture tools for biomedical research by creating robust three-dimensional (3D) architecture to recapitulate the primary tissues' cellular heterogeneity, structure, and functions. Such organoid technology enables researchers to re-create human organs and diseases model in a culture dish. It thus holds excellent promises for many translational applications such as regenerative medicine, drug discovery, and precision medicine. This review summarizes the current knowledge on the progression and promotion of organoid models, particularly with the heart disease approach. We discuss the usefulness of clinical applications of cardiac organoids and ultimately highlight the currently advanced therapeutic strategies in vitro model of organoids aimed at personalizing heart disease treatment.

This review covers nanotherapeutic strategies for solving the global problems associated with Alzheimer's disease (AD). The most dramatic factor contributing humanistic, social and economic urgency of the situation is the incurability of the disease, with the drug intervention addressing only AD symptoms and retarding their progress. Key sources behind these challenges are the inability of the early diagnosis of AD, the lack of comprehensive information on the molecular mechanism of the pathogenesis, the bloodbrain barrier obstacles, and the insufficient effectiveness of currently available drugs and therapeutic strategies. The application of nanocarriers allows part of these problems to be solved, together with the improvement of drug bioavailability, prolonged circulation, and overcoming/bypassing the biological barriers. To this date, numerous types and subtypes of nanocarriers are developed and reviewed, the majority of which can be adapted for the treatment of various diseases. Therefore, herein, nanotherapy strategies are specifically categorized in term of the administration routes of AD medicines, with the noninvasive, i.e., transdermal, oral, and intranasal routes emphasized. Further, benefits/ limitations of various nanocarriers are discussed, and perspectives of their application are highlighted.

Background: Although radiotherapy is one of the main cancer treatment modalities, exposing healthy organs/tissues to ionizing radiation during treatment can lead to different adverse effects. In this regard, it has been shown that the use of radioprotective agents may alleviate the ionizing radiation-induced toxicities. Objective: The present study aims to review the radioprotective potentials of silymarin/silibinin in the prevention/reduction of ionizing radiation-induced adverse effects on healthy cells/tissues. Methods: Based on PRISMA guidelines, a comprehensive and systematic search was performed for identifying relevant literature on the “potential protective role of silymarin/silibinin in the treatment of radiotherapy-induced toxicities” in the different electronic databases of Web of Science, PubMed, and Scopus up to April 2022. Four hundred and fifty-five articles were obtained and screened in accordance with the inclusion and exclusion criteria of the current study. Finally, 19 papers were included in this systematic review. Results: The findings revealed that the ionizing radiation-treated groups had reduced survival rates and body weight in comparison with the control groups. It was also found that radiation can induce mild to severe adverse effects on the skin, digestive, hematologic, lymphatic, respiratory, reproductive, and urinary systems. Nevertheless, the administration of silymarin/silibinin could mitigate the ionizing radiation-induced adverse effects in most cases. This herbal agent exerts its radioprotective effects through anti-oxidant, anti-apoptosis, anti-inflammatory activities, and other mechanisms. Conclusion: The results of the current systematic review showed that co-treatment of silymarin/silibinin with radiotherapy alleviates the radiotherapy-induced adverse effects in healthy cells/tissues.

Background: Circulating microRNAs (miRNAs, miRs) are now used as noninvasive diagnostic indicators in various malignancies. Objective: Our objective is to use a meta-analysis to assess the diagnostic performance of circulating miRNAs in gastric cancer. Methods: We reviewed databases and methodically obtained papers for analysis until October 15th, 2021. The random-effect meta-analysis was performed to construct pooled diagnostic parameters. To detect the causes of heterogeneity, spearman threshold effect analysis and subgroup analysis were performed. The I² and Chi-square tests were also used to examine the heterogeneity. The subgroup analyses were conducted based on sample types (serum/plasma/blood), normalized genes (U6, miR-16, and miR-39), qPCR mastermix (SYBR and Taqman), and country. Finally, the publication bias was estimated using Egger's funnel plot asymmetry test. Results: A total of 40 articles covering 73 studies (59 microRNAs) were included, containing 11,022 participants (6,324 cases and 4,698 controls). The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.75 (95% CI: 0.74-0.77), 0.79 (95% CI: 0.78-0.80), 4.081 (95% CI: 3.43-4.85), 0.28 (95% CI: 0.25-0.32), 16.08 (95% CI: 12.34-20.95), and 0.877 (CI: 0.84-0.90), respectively. We conducted a subgroup analysis of diagnostic values, which revealed that serum type, U6 reference gene, SYBR mastermix, and East Asian Countries (China and Japan) had better diagnostic value. Conclusion: Circulating miRs can serve as diagnostic biomarkers for gastric cancer. However, specific miRNAs still need to be discovered in diagnosing gastric cancer, especially early screening.

Background: Cervical cancer is one of the most common types of cancer among women. Therefore, cancer studies are underway for a new chemo-agent with more effect on cancer cells and fewer side effects on normal human healthy cells. The currently studied novel ligand L2b as a reduced salicylaldimine derivative was examined in seven cell lines, HeLa, DU-145, PC3, DLD-1, ECC, HT-29, and PNT1-A as a control. Aim: Because of the antiproliferative ability of L2b, this study intends to look at the apoptotic, cytotoxic, and genotoxic activity of L2b on HeLa. Methods: For this purpose, MTT assay is for screening cytotoxic effects, comet assay for looking for DNA damaging or genotoxicity levels, ELISA and DNA fragmentation for apoptotic measuring, AO/EB stain test for checking the rates of live, apoptotic and necrotic cells were performed. To reveal the oxidative state, OSI was assessed by total oxidant and antioxidant status ratios. FRAP assay was calculated for ferric-reducing antioxidant power, using total thiol and GSH assays to measure the antioxidant values of HeLa cells. Results: Of this result, we have found a tremendous effect of L2b on HeLa cells, especially in raising the ROS rate, damaging their DNA, and causing a range of reactions leading to apoptosis. Conclusion: In conclusion, the data predict which ligand L2b is capable of rising apoptosis in vitro cervical cancer cell line studied. Further cancer studies are needed to reveal the apoptosis pathways of the ligand L2b in the HeLa cell line and its anticancer drug potency in vivo work.