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Topic Review
Sirtuins in Breast and Prostate Cancer
In mammals, seven sirtuins (SIRT1–7) have been identified, which primarily function as NAD-dependent deacetylases (SIRT1–3 and SIRT5–7) and ADP-ribosyl transferases (SIRT4 and 6). Additionally, sirtuins have been reported to function as demyristoylases (SIRT1–3 and 6), lipoamidases (SIRT4), and desuccinylases/demalonylases/deglutarylases (SIRT5). The forcus herein is the information on the tumor promotion or suppression roles of SIRT1–7 in breast and prostate cancers. Precisely, it is highlighted that sirtuins regulate various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of both breast and prostate cancer.
  • 976
  • 03 Nov 2022
Topic Review
Bioactivity of Steroidal Arylidene Derivatives
Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems, in addition to their relevant bioactivity with potential pharmacological interest. 
  • 975
  • 29 Apr 2021
Topic Review
Myzus persicae Sulzer
The green peach aphid (Myzus persicae Sulzer), a major and harmful chili aphid usually managed using chemical pesticides, is responsible for massive annual agricultural losses. The efficacy of two protein elicitors, PeaT1 and PeBC1, to stimulate a defensive response against M. persicae in chili was studied in this study.
  • 975
  • 11 Nov 2021
Topic Review
PTP1B Inhibitors
Protein-tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling pathways and plays an important role in type 2 diabetes mellitus (T2DM), as its overexpression may induce insulin resistance.
  • 975
  • 21 Jan 2022
Topic Review
Biomarker Detection in Colorectal Cancer Diagnosis
Globally, colorectal cancer (CRC) is the third most common cancer, with 1.4 million new cases and over 700,000 deaths per annum. Despite being one of the most common cancers, few molecular approaches to detect CRC exist. Carcinoembryonic antigen (CEA) is a known serum biomarker that is used in CRC for monitoring disease recurrence or response to treatment. However, it can also be raised in multiple benign conditions, thus having no value in early detection or screening for CRC. Molecular biomarkers play an ever-increasing role in the diagnosis, prognosis, and outcome prediction of disease, however, only a limited number of biomarkers are available and none are suitable for early detection and screening of CRC. A PCR-based Epi proColon® blood plasma test for the detection of methylated SEPT9 has been approved by the USFDA for CRC screening in the USA, alongside a stool test for methylated DNA from CRC cells. However, these are reserved for patients who decline traditional screening methods. There remains an urgent need for the development of non-invasive molecular biomarkers that are highly specific and sensitive to CRC and that can be used routinely for early detection and screening. A molecular approach to the discovery of CRC biomarkers focuses on the analysis of the transcriptome of cancer cells to identify differentially expressed genes and proteins. A systematic search of the literature yielded over 100 differentially expressed CRC molecular markers, of which the vast majority are overexpressed in CRC. In terms of function, they largely belong to biological pathways involved in cell division, regulation of gene expression, or cell proliferation, to name a few. 
  • 975
  • 05 May 2022
Topic Review
Flavonoids-Based Delivery Systems towards Cancer Therapies
Cancer is the second leading cause of death worldwide. Cervical cancer, for instance, is considered a major scourge in low-income countries. Its development is mostly associated with the human papillomavirus persistent infection and despite the availability of preventive vaccines, they are only widely administered in more developed countries, thus leaving a large percentage of unvaccinated women highly susceptible to this type of cancer. The treatments are based on invasive techniques, being far from effective. Therefore, the search for novel, advanced and personalized therapeutic approaches is imperative. Flavonoids belong to a group of natural polyphenolic compounds, well recognized for their great anticancer capacity, thus promising to be incorporated in cancer therapy protocols. However, their use is limited due to their low solubility, stability and bioavailability. Several types of flavonoid-based delivery systems are being developed for anticancer therapy, namely for cervical cancer. The consideration of these new forms of delivery systems allows for the use of fewer flavonoids as well as permits the use of ligands that efficiently target these systems to cancer cells, therefore reducing the risk of toxicity in healthy cells and improving their therapeutic effect. A variety of delivery systems for the encapsulation of these drugs can be explored, depending on the material considered and the properties exhibited by the drug.
  • 975
  • 08 Jul 2022
Topic Review
Preserving Adult Endothelium Health and Reversing Its Dysfunction
The endothelium has multiple functions, ranging from maintaining vascular homeostasis and providing nutrition and oxygen to tissues to evocating inflammation under adverse conditions and determining endothelial barrier disruption, resulting in dysfunction. Endothelial dysfunction represents a common condition associated with the pathogenesis of all diseases of the cardiovascular system, as well as of diseases of all of the other systems of the human body, including sepsis, acute respiratory distress syndrome, and COVID-19 respiratory distress. Such evidence is leading to the identification of potential biomarkers and therapeutic targets for preserving, reverting, or restoring endothelium integrity and functionality by promptly treating its dysfunction.
  • 975
  • 14 Jul 2022
Topic Review
Cell-Free DNA and Bladder Cancer
Bladder cancer (BC) is the 10th most frequent cancer in the world. The initial diagnosis and surveillance of BC require a combination of invasive and non-invasive methods, which are costly and suffer from several limitations. Cystoscopy with urine cytology and histological examination presents the standard diagnostic approach. Various biomarkers (e.g., proteins, genes, and RNAs) have been extensively studied in relation to BC.
  • 975
  • 24 Nov 2022
Topic Review
CRISPR/Cas-Mediated Genome Editing in Insects
Insect pests impose a serious threat to agricultural productivity. Initially, for pest management, several breeding approaches were applied which have now been gradually replaced by genome editing (GE) strategies as they are more efficient and less laborious. Due to its specificity and easy handling, CRISPR/Cas9-based genome editing has been applied to a wide range of organisms for various research purposes. For pest control, diverse approaches have been applied utilizing CRISPR/Cas9-like systems, thereby making the pests susceptible to various insecticides, compromising the reproductive fitness of the pest, hindering the metamorphosis of the pest, and there have been many other benefits. 
  • 975
  • 30 Nov 2022
Topic Review
Fluorescent Biosensors for Chemotherapy Development
Genetically-encoded fluorescent sensors have been actively developed over the last few decades and used in live imaging and drug screening. Real-time monitoring of drug action in a specific cellular compartment, organ, or tissue type; the ability to screen at the single-cell resolution; and the elimination of false-positive results caused by low drug bioavailability that is not detected by in vitro testing methods are a few of the obvious benefits of using genetically-encoded fluorescent sensors in drug screening. In combination with high-throughput screening (HTS), some genetically encoded fluorescent sensors may provide high reproducibility and robustness to assays. Here, we provide an overview of attempts at using genetically encoded fluorescent sensors in HTS of anticancer compounds.
  • 974
  • 21 Jan 2021
Topic Review
DNA-Dependent Protein Kinase in Non-Homologous End Joining
DNA-dependent protein kinase (DNA-PK), which is composed of a DNA-PK catalytic subunit (DNA-PKcs) and Ku80-Ku70 heterodimer, acts as the molecular sensor for DSB and plays a pivotal role in DSB repair through non-homologous end joining (NHEJ). Cells deficient for DNA-PKcs show hypersensitivity to IR and several DNA-damaging agents. Cellular sensitivity to IR and DNA-damaging agents can be augmented by the inhibition of DNA-PK. A number of small molecules that inhibit DNA-PK have been developed. 
  • 974
  • 05 May 2022
Topic Review
Role of Branched-Chain Amino Acids in Liver Diseases
Chronic liver diseases pose a substantial health burden worldwide, with approximately two million deaths each year. Branched-chain amino acids (BCAAs)—valine, leucine, and isoleucine—are a group of essential amino acids that are essential for human health. Despite the necessity of a dietary intake of BCAA, emerging data indicate the undeniable correlation between elevated circulating BCAA levels and chronic liver diseases, including non-alcoholic fatty liver diseases (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). 
  • 974
  • 30 Jun 2022
Topic Review
Liver-Associated Injuries in COVID-19 Patients
The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. 
  • 974
  • 13 Jan 2023
Topic Review
FLT3 Tyrosine Kinase Inhibitors
FLT3 is a member of the class III receptor tyrosine kinase family that exerts a key role in the proliferation and differentiation of hematopoietic progenitor cells. FLT3 inhibitors have dramatically altered the prognosis of the FLT3 mutant AML.
  • 972
  • 10 Jun 2021
Topic Review
Zebrafish and High-Throughput Cardiac Research
Heart disease is the leading cause of death in the United States and worldwide. Understanding the molecular mechanisms of cardiac development and regeneration will improve diagnostic and therapeutic interventions against heart disease. In this direction, zebrafish is an excellent model because several processes of zebrafish heart development are largely conserved in humans, and zebrafish has several advantages as a model organism. Zebrafish transcriptomic profiles undergo alterations during different stages of cardiac development and regeneration which are revealed by RNA-sequencing. ChIP-sequencing has detected genome-wide occupancy of histone post-translational modifications that epigenetically regulate gene expression and identified a locus with enhancer-like characteristics. ATAC-sequencing has identified active enhancers in cardiac progenitor cells during early developmental stages which overlap with occupancy of histone modifications of active transcription as determined by ChIP-sequencing. 
  • 972
  • 31 Dec 2021
Topic Review
Yeast as a Model for VPS13-Dependent Neurodegenerative Diseases
Mutations in human VPS13A-D genes result in rare neurological diseases, including chorea-acanthocytosis (ChAc). The pathogenesis of these diseases is poorly understood, and no effective treatment is available. As VPS13 genes are evolutionarily conserved, the effects of the pathogenic mutations could be studied in model organisms, including yeast, where one VPS13 gene is present. Here, the researchers summarize advancements obtained using yeast. In recent studies, vps13Δ and vps13-I2749 yeast mutants, which are models of chorea-acanthocytosis, were used to screen for multicopy and chemical suppressors. Two of the suppressors, a fragment of the MYO3 and RCN2 genes, act by downregulating calcineurin activity. In addition, vps13Δ suppression was achieved by using calcineurin inhibitors. The other group of multicopy suppressors were genes: FET4, encoding iron transporter, and CTR1, CTR3 and CCC2, encoding copper transporters. Mechanisms of their suppression rely on causing an increase in the intracellular iron content. Moreover, among the identified chemical suppressors were copper ionophores, which require a functional iron uptake system for activity, and flavonoids, which bind iron. These findings point at areas for further investigation in a higher eukaryotic model of VPS13-related diseases and to new therapeutic targets: calcium signalling and copper and iron homeostasis. Furthermore, the identified drugs are interesting candidates for drug repurposing for these diseases.
  • 972
  • 18 May 2022
Topic Review
Receptor-Arrestin Interactions
Arrestins are a small family of four proteins in most vertebrates that bind hundreds of different G protein-coupled receptors (GPCRs). Arrestin binding to a GPCR has at least three functions: precluding further receptor coupling to G proteins, facilitating receptor internalization, and initiating distinct arrestin-mediated signaling. The molecular mechanism of arrestin–GPCR interactions has been extensively studied and discussed from the “arrestin perspective”, focusing on the roles of arrestin elements in receptor binding.
  • 971
  • 19 Feb 2021
Topic Review
PGC-1s in Parkinson’s Disease
The family of peroxisome proliferator-activated receptor γ coactivator 1 comprises three members, PGC-1α, PGC-1β, and PGC-related coactivator (PRC). PGC-1s act as ‘molecular switches’ in many metabolic pathways, coordinating transcriptional programs involved in the control of cellular metabolism and overall energy homeostasis as well as antioxidant defence.
  • 971
  • 28 Apr 2021
Topic Review
Pharmaceutical Drug and Metabolic Adaptions/Reprogramming in β-Cells
Islet inflammation in T1DM is characterized by leukocyte infiltrates, in particular macrophages and T-cells which damage β-cells by release of cytokines, ROS and NO and also activation of death-receptor-mediated death pathways and subsequent phagocytosis. Production of cytokines such as INF-γ, TNFα and IL-1β act in synergy to promote elevation in concentration and increase in activity of NADPH oxidase and iNOS consequently increasing the formation of products including ROS and NO, respectively. The mechanism of action of INF-γ, TNFα and IL-1β involves stimulation of transcription factors including NFκB (in mouse islet β-cells).
  • 971
  • 29 Mar 2022
Topic Review
Biological Activities of Rice Phytoalexins
Domesticated rice (Oryza sativa L., Poaceae) is one of the widely grown food crops worldwide and is the primary food source in many countries, especially but not only in Asia. Unlike other staple cereal crops, most rice production is used for human consumption in the form of whole-husked grains. In addition to being a primary source of carbohydrates, proteins, and other essential nutrients, rice provides a wide range of bioactive secondary metabolites, including phenolic acids, flavonoids, terpenoids, steroids, and alkaloids. Wild and cultivated rice species are known to possess a wide variety of antimicrobial secondary metabolites, known as phytoalexins, which are part of their active defense mechanisms. These compounds are biosynthesized transiently by rice in response to pathogens and certain abiotic stresses. 
  • 971
  • 31 Jan 2023
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