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Medicines, Volume 11, Issue 1 (January 2024) – 3 articles

Cover Story (view full-size image): Medicines (ISSN 2305-6320) is an international, peer-reviewed, and open access journal aimed at combining all areas of medical disciplines and subspecialties in one platform. It mainly publishes, but is not limited to, original research papers, case reports, reviews, systematic reviews, brief reports, concepts and opinions on all aspects of basic, clinical, and translational research in relation to human health. The journal will accept manuscripts on medical concepts that include evidence-based medicine and/or alternative medicine. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Full details must be provided when publishing an experiment so that the results can be reproduced.
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12 pages, 2190 KiB  
Article
Dimeric 3,5-Bis(benzylidene)-4-piperidones: Tumor-Selective Cytotoxicity and Structure-Activity Relationships
by Swagatika Das, Praveen K. Roayapalley, Hiroshi Sakagami, Naoki Umemura, Dennis K. J. Gorecki, Mohammad Hossain, Masami Kawase, Umashankar Das and Jonathan R. Dimmock
Medicines 2024, 11(1), 3; https://doi.org/10.3390/medicines11010003 - 11 Jan 2024
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Abstract
Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers [...] Read more.
Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers of 3,5-bis(benzylidene)-4-piperidones against human malignant cells (promyelocytic leukemia HL-60 and squamous cell carcinoma HSC-2, HSC-3, and HSC-4). Methods: Tumor specificity was evaluated by the selectivity index (SI), that is the ratio of the mean CC50 for human non-malignant oral cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) to that for malignant cells. Results: The compounds were highly toxic to human malignant cells. On the other hand, these molecules were less toxic to human non-malignant cells. In particular, a potent lead molecule, 3b, was identified. A QSAR study revealed that the placement of electron-releasing and hydrophilic substituents into the aryl rings led to increases in cytotoxic potencies. The modes of action of a lead compound discovered in this study designated 3b were the activation of caspases-3 and -7, as well as causing PARP1 cleavage and G2 arrest, followed by sub-G1 accumulation in the cell cycle. This compound also depolarized the mitochondrial membrane and generated reactive oxygen species in human colon carcinoma HCT116 cells. In conclusion, this study has revealed that, in general, the compounds described in this report are tumor-selective cytotoxins. Full article
(This article belongs to the Section Cancer Biology and Anticancer Therapeutics)
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16 pages, 7769 KiB  
Article
Expression Profiles of Hypoxia-Related Genes of Cancers Originating from Anatomically Similar Locations Using TCGA Database Analysis
by Hye Lim Bae, Kyeonghun Jeong, Suna Yang, Hyeji Jun, Kwangsoo Kim and Young Jun Chai
Medicines 2024, 11(1), 2; https://doi.org/10.3390/medicines11010002 - 31 Dec 2023
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Abstract
Background: Hypoxia is a well-recognized characteristic of the tumor microenvironment of solid cancers. This study aimed to analyze hypoxia-related genes shared by groups based on tumor location. Methods: A total of 9 hypoxia-related pathways from the Kyoto Encyclopedia of Genes and Genomes database [...] Read more.
Background: Hypoxia is a well-recognized characteristic of the tumor microenvironment of solid cancers. This study aimed to analyze hypoxia-related genes shared by groups based on tumor location. Methods: A total of 9 hypoxia-related pathways from the Kyoto Encyclopedia of Genes and Genomes database or the Reactome database were selected, and 850 hypoxia-related genes were analyzed. Based on their anatomical locations, 14 tumor types were categorized into 6 groups. The group-specific genetic risk score was classified as high- or low-risk based on mRNA expression, and survival outcomes were evaluated. Results: The risk scores in the Female Reproductive group and the Lung group were internally and externally validated. In the Female Reproductive group, CDKN2A, FN1, and ITGA5 were identified as hub genes associated with poor prognosis, while IL2RB and LEF1 were associated with favorable prognosis. In the Lung group, ITGB1 and LDHA were associated with poor prognosis, and GLS2 was associated with favorable prognosis. Functional enrichment analysis showed that the Female Reproductive group was enriched in relation to cilia and skin, while the Lung group was enriched in relation to cytokines and defense. Conclusions: This analysis may lead to better understanding of the mechanisms of cancer progression and facilitate establishing new biomarkers for prognosis prediction. Full article
(This article belongs to the Section Cancer Biology and Anticancer Therapeutics)
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10 pages, 756 KiB  
Article
The Impact of Comorbidities and Demographic Factors on Ejection Fraction
by Cezara Andreea Soysaler, Cătălina Liliana Andrei, Octavian Ceban and Crina Julieta Sinescu
Medicines 2024, 11(1), 1; https://doi.org/10.3390/medicines11010001 - 19 Dec 2023
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Abstract
Heart failure (HF) presents an increasingly significant problem as the population ages. The cause of HF plays a significant role in determining treatment options and outcomes. It is worth noting that several studies have identified gender disparities in both morbidity and mortality, which [...] Read more.
Heart failure (HF) presents an increasingly significant problem as the population ages. The cause of HF plays a significant role in determining treatment options and outcomes. It is worth noting that several studies have identified gender disparities in both morbidity and mortality, which may suggest differing causes of HF. The purpose of this research is to investigate the influence of various factors, including demographics and comorbidities, on ejection fraction (EF). The objectives of this study involve implementing preventive measures, ensuring timely diagnosis, and implementing interventions that target risk factors and specific comorbidities. These efforts aim to improve the prognosis for individuals affected by heart failure. The main method consists of linear regression. The demographic factors under scrutiny are gender and education, while the comorbidities of interest encompass valvulopathy, ischemia, smoking, obesity, high cholesterol, and diabetes. The main results consist of the fact that high education is associated with a 12.8% better EF on average, while among the factors with a negative role analyzed, ischemia is the most harmful, being 12.8% lower on average. Factors with a smaller impact are smoking, obesity, and high cholesterol. Diabetes does not seem to affect EF. Full article
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