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Topic Review
Trichomonas vaginalis
In Trichomonas, the hydrogenosome, a double membrane-bounded organelle that produces ATP, also can be a good target. Other structures include mitosomes, ribosomes, and proteasomes. Metronidazole is the most frequent compound used to kill many anaerobic organisms, including Giardia and Trichomonas. It enters the cell by passive diffusion and needs to find a highly reductive environment to be reduced to the nitro radicals to be active. However, it provokes several side effects, and some strains present metronidazole resistance. Therefore, to improve the quality of the chemotherapy against parasitic protozoa is important to invest in the development of highly specific compounds that interfere with key steps of essential metabolic pathways or in the functional macromolecular complexes which are most often associated with cell structures and organelles. 
  • 489
  • 15 Nov 2022
Topic Review
Extracellular Matrix Environment of ccRCC
The extracellular matrix (ECM) controls fundamental properties of tumors, including growth, blood vessel investment, and invasion. The ECM defines rigidity of tumor tissue and individual ECM proteins have distinct biological effects on tumor cells. The most frequent initiating genetic mutation in ccRCC (clear cell renal cell carcinoma) inactivates the VHL gene, which plays a direct role in organizing the ECM.
  • 489
  • 15 Sep 2022
Topic Review
Tocotrienols
Tocotrienols (T3s), members of the vitamin E family, are natural compounds found in various food sources and exist as four naturally occurring analogues known as alpha (α), beta (β), delta (δ), and gamma (γ).
  • 488
  • 29 Nov 2021
Topic Review
Precision Medicine in Rare Diseases
The own patient-derived cells can be used to perform personalized pharmacological screening in genetic rare diseases. For precision medicine to be successful at the therapeutic level, in addition of the information provide from genomics, pharmacogenomics, metabolomics and proteomics, our proposal argues that it is also necessary to know the cellular response, and therefore the behavior of particular mutations in vitro, to various therapeutic options. Precision medicine relies on the assumption that different mutations and marked inter-individual genetic variation can contribute significantly to drug response. The goal of personalized medicine is to maximize the probability of therapeutic efficacy for an individual patient.
  • 488
  • 23 Nov 2020
Topic Review
Autophagy in Multiple Myeloma
Multiple myeloma (MM) is the second most prevalent hematologic malignancy. One of the significant obstacles in treating most MM patients is drug resistance, especially for individuals who have experienced relapses or developed resistance to such cutting-edge treatments. One of the critical processes in developing drug resistance in MM is autophagic activity, an intracellular self-digestive process. In multiple myeloma, it has been shown that High mobility group box protein 1 (HMGB1)-dependent autophagy can contribute to drug resistance.
  • 488
  • 10 Apr 2023
Topic Review
Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases
The 26S proteasome is the principal protease for regulated intracellular proteolysis. This multi-subunit complex is also pivotal for clearance of harmful proteins that are produced throughout the lifetime of eukaryotes. Recent structural and kinetic studies have revealed a multitude of conformational states of the proteasome in substrate-free and substrate-engaged forms. These conformational transitions demonstrate that proteasome is a highly dynamic machinery during substrate processing that can be also controlled by a number of proteasome-associated factors. Essentially, three distinct family of deubiquitinases–USP14, RPN11, and UCH37–are associated with the 19S regulatory particle of human proteasome. USP14 and UCH37 are capable of editing ubiquitin conjugates during the process of their dynamic engagement into the proteasome prior to the catalytic commitment. In contrast, RPN11-mediated deubiquitination is directly coupled to substrate degradation by sensing the proteasome’s conformational switch into the commitment steps. 
  • 487
  • 23 Jun 2021
Topic Review
CD137+ T-Cells
The CD137 receptor is expressed by activated antigen-specific T-cells. CD137+ T-cells were identified inside TILs and PBMCs of different tumor types and have proven to be the naturally occurring antitumor effector cells, capable of expressing a wide variability in terms of TCR specificity against both shared and neoantigenic tumor-derived peptides. The aim of this review is thus summarizing and highlighting their role as drivers of patients’ immune responses in anticancer therapies as well as their potential role in future and current strategies of immunotherapy.
  • 487
  • 08 Mar 2021
Topic Review
Xanthohumol Is a Potent Pan-Inhibitor of Coronaviruses
Coronaviruses cause diseases in humans and livestock. The SARS-CoV-2 is infecting millions of human beings, with high morbidity and mortality worldwide. The main protease (Mpro) of coronavirus plays a pivotal role in viral replication and transcription, which, in theory, is an attractive drug target for antiviral drug development. It has been extensively discussed whether Xanthohumol is able to help COVID-19 patients. Here, researchers report that Xanthohumol, a small molecule in clinical trials from hops (Humulus lupulus), was a potent pan-inhibitor for various coronaviruses by targeting Mpro, for example, betacoronavirus SARS-CoV-2 (IC50 value of 1.53 μM), and alphacoronavirus PEDV (IC50 value of 7.51 μM). Xanthohumol inhibited Mpro activities in the enzymatical assays, while pretreatment with Xanthohumol restricted the SARS-CoV-2 and PEDV replication in Vero-E6 cells. Therefore, Xanthohumol is a potent pan-inhibitor of coronaviruses and an excellent lead compound for further drug development.
  • 487
  • 22 Dec 2021
Topic Review
Mitochondrial Metabolism and Hematopoietic Stem Cell Aging
Mitochondrial dysfunction and stem cell exhaustion are two hallmarks of aging. In the hematopoietic system, aging is linked to imbalanced immune response and reduced regenerative capacity in hematopoietic stem cells (HSCs), as well as an increased predisposition to a spectrum of diseases, including myelodysplastic syndrome and acute myeloid leukemia.
  • 487
  • 20 Oct 2021
Topic Review
Hypoxia-Inducible Factors in Osteogenesis
As central mediators of homeostasis, hypoxia-inducible transcription factors (HIFs) can allow cells to survive in a low-oxygen environment and are essential for the regulation of osteogenesis and skeletal repair.
  • 487
  • 13 Oct 2022
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