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Topic Review
Pre-clinical Cerebral Perfusion MRI Techniques
Alterations to the cerebral microcirculation have been recognized to play a crucial role in the development of neurodegenerative disorders. However, the exact role of the microvascular alterations in the pathophysiological mechanisms often remains poorly understood. The early detection of changes in microcirculation and cerebral blood flow (CBF) can be used to get a better understanding of underlying disease mechanisms. This could be an important step towards the development of new treatment approaches. Animal models allow for the study of the disease mechanism at several stages of development, before the onset of clinical symptoms, and the verification with invasive imaging techniques. Specifically, pre-clinical magnetic resonance imaging (MRI) is an important tool for the development and validation of MRI sequences under clinically relevant conditions. This article reviews MRI strategies providing indirect non-invasive measurements of microvascular changes in the rodent brain that can be used for early detection and characterization of neurodegenerative disorders. The perfusion MRI techniques: Dynamic Contrast Enhanced (DCE), Dynamic Susceptibility Contrast Enhanced (DSC) and Arterial Spin Labeling (ASL), will be discussed, followed by less established imaging strategies used to analyze the cerebral microcirculation: Intravoxel Incoherent Motion (IVIM), Vascular Space Occupancy (VASO), Steady-State Susceptibility Contrast (SSC), Vessel size imaging, SAGE-based DSC, Phase Contrast Flow (PC) Quantitative Susceptibility Mapping (QSM) and quantitative Blood-Oxygenation-Level-Dependent (qBOLD). We will emphasize the advantages and limitations of each strategy, in particular on applications for high-field MRI in the rodent’s brain. 
  • 1.1K
  • 02 Jun 2021
Topic Review
Legacy Effect in Cardiovascular Disease
The "legacy effect" describes the long-term benefits that may persist for many years after the end of an intervention period, involving different biological processes. The legacy effect in cardiovascular disease (CVD) prevention has been evaluated by a limited number of studies, mostly based on pharmacological interventions, while few manuscripts on dietary interventions have been published. Most of these studies are focused on intensive treatment regimens, whose main goal is to achieve tight control of one or more cardiovascular risk factors. 
  • 1.1K
  • 16 Nov 2020
Topic Review
Mechanisms of Cisplatin Resistance in Germ Cell Tumors
Testicular germ cell tumors (GCTs) are highly curable malignancies. Excellent survival rates in patients with metastatic disease can be attributed to the exceptional sensitivity of GCTs to cisplatin-based chemotherapy. This hypersensitivity is probably related to alterations in the DNA repair of cisplatin-induced DNA damage, and an excessive apoptotic response. However, chemotherapy fails due to the development of cisplatin resistance in a proportion of patients, who are then considered “platinum-refractory”. 
  • 1.1K
  • 24 Jun 2022
Topic Review
Advances in Histone Demethylase KDM3A
Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors.
  • 1.1K
  • 19 Oct 2020
Topic Review
Echocardiography in Autoimmune Rheumatic Diseases
Echocardiography, including transthoracic two and three-dimensional echocardiography, Doppler imaging, myocardial deformation and transesophageal echo, is an established and widely available imaging technique for the identification of cardiovascular manifestations that are crucial for prognosis in rheumatic diseases. Echocardiography is also important for monitoring the impact of drug treatment on cardiac function, coronary microcirculatory function, valvular function and pulmonary artery pressures. 
  • 1.1K
  • 17 Sep 2020
Topic Review
Persufflation (PSF)
Persufflation (PSF) utilises the organ's own vascular network to provide oxygen to the organ tissue and maintain metabolism during preservation to avoid hypoxic damage. This method discovered in the early 20th century has shown promise in providing both longer-term preservation and organ reconditioning capabilities for multiple organs including the liver, kidneys, and pancreas.
  • 1.1K
  • 11 Nov 2021
Topic Review
Liquid Biopsy in Colorectal Cancer
There is a critical need for new diagnostic and prognostic biomarkers with high specificity and sensitivity in patients with colorectal cancer (CRC). Liquid biopsy could represent the new era for biomarkers detection: the term “liquid biopsy” refers to the isolation of cancer-derived components, such as circulating tumor cells (CTC), circulating tumor DNA (ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and proteins, from peripheral blood or other body fluids (i.e., ascites, urine, pleural effusion, and cerebrospinal fluid), and their genomic or proteomic assessment. Furthermore, exosomes (EXOs) which are membrane-bound extracellular vesicles containing proteins and nucleic acids released in the bloodstream by cancer cells, could represent potential biomarkers. 
  • 1.1K
  • 09 Nov 2020
Topic Review
Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management
Artemisia annua (“sweet wormwood”, “qinghao”), a member of the Asteraceae family, has been traditionally used safely over the centuries to treat a variety of fevers, and notably, ‘‘intermittent fevers” and chills-related conditions, including respiratory tract infections. It also exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19 related symptoms. A. annua is a source of artemisinin, which is active against malaria, and also exhibits potential to fight against the SARS-CoV-2 infection by inhibiting its invasion, and replication, as well as reducing oxidative stress and inflammation, and mitigating lung damage.
  • 1.1K
  • 07 Jul 2022
Topic Review
Melatonin
Melatonin, the nocturnally released pineal hormone, has attracted great attention due to its pleiotropic roles. Although its major role is the regulation of the circadian rhythm, this indoleamine engages in multiple mechanisms, including neurogenesis, antioxidation, and inflammatory responses. Apart from its versatility, this molecule has also gained a reputation as being potentially tumor suppressive, espe-cially in hormone-dependent cancers . Melatonin is able to selectively neutralize the estrogenic effects on the breast. The oncostatic roles of melatonin are based on its diverse effects, including its antioxidative properties, apoptosis induction, and an-ticancer immunity . Interestingly, melatonin is able to protect normal cells from the cytotoxicity accompanied by ionizing radiation (IR). This non-targeted effect fol-lowing IR is alleviated via melatonin-mediated regulation of prostaglandins, Toll-like receptors (TLRs), and transcription factors . Additionally, melatonin has been proposed to enhance the therapeutic efficacy of IR, suggesting that this hormone could be a potential radiosensitizer . The radiosensitization of breast cancer cells by mel-atonin is mediated through reduced cell proliferation, the facilitation of cell cycle ar-rest, downregulated DNA repair, and increased p53 mRNA levels .
  • 1.1K
  • 12 Jan 2021
Topic Review
ACHP Targets the STAT3
STAT3 is an oncogenic transcription factor that regulates the expression of genes which are involved in malignant transformation. Aberrant activation of STAT3 has been observed in a wide range of human malignancies and its role in negative prognosis is well-documented. In this report, we performed high-throughput virtual screening in search of STAT3 signaling inhibitors using a cheminformatics platform and identified 2-Amino-6-[2-(Cyclopropylmethoxy)-6-Hydroxyphenyl]-4-Piperidin-4-yl Nicotinonitrile (ACHP) as the inhibitor of the STAT3 signaling pathway. The predicted hit was evaluated in non-small cell lung cancer (NSCLC) cell lines for its STAT3 inhibitory activity. In vitro experiments suggested that ACHP decreased the cell viability and inhibited the phosphorylation of STAT3 on Tyr705 of NSCLC cells. In addition, ACHP imparted inhibitory activity on the constitutive activation of upstream protein tyrosine kinases, including JAK1, JAK2, and Src. ACHP decreased the nuclear translocation of STAT3 and downregulated its DNA binding ability. Apoptosis was evidenced by cleavage of caspase-3 and PARP with the subsequent decline in antiapoptotic proteins, including Bcl-2, Bcl-xl, and survivin. Overall, we report that ACHP can act as a potent STAT3 signaling inhibitor in NSCLC cell lines.
  • 1.1K
  • 28 Oct 2020
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