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Topic Review
VEGF/VEGFR Axis for Cancer Therapy
The vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) axis is indispensable in the process of angiogenesis and has been implicated as a key driver of tumor vascularization. Consequently, several strategies that target VEGF and its cognate receptors, VEGFR-1 and VEGFR-2, have been designed to treat cancer. While therapies targeting full-length VEGF have resulted in an improvement in both overall survival and progression-free survival in various cancers, these benefits have been modest. In addition, the inhibition of VEGFRs is associated with undesirable off-target effects. Moreover, VEGF splice variants that modulate sprouting and non-sprouting angiogenesis have been identified. Cues within the tumor microenvironment determine the expression patterns of these variants. Noteworthy is that the mechanisms of action of these variants challenge the established norm of VEGF signaling.
  • 628
  • 15 Dec 2022
Topic Review
Mesenchymal-Stromal-Cell-Conditioned Media
Despite significant advances in biomedical research, osteochondral defects resulting from injury, an autoimmune condition, cancer, or other pathological conditions still represent a significant medical problem. Cell-based therapies and tissue engineering have gradually become promising alternatives. They combine the use of different types of cells and biomaterials to induce regeneration processes or replace damaged osteochondral tissue. One of the main challenges of this approach before clinical translation is the large-scale in vitro expansion of cells without changing their biological properties, while the use of conditioned media which contains various bioactive molecules appears to be very important.
  • 628
  • 28 May 2023
Topic Review
Vascular Endothelial Cell Senescence and Death
Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood.
  • 628
  • 17 Oct 2023
Topic Review
Methylation in Period2 (PER2) Transcription
It has been proposed that carbon monoxide (CO) is a chemical light carrier that is transferred by the humoral pathway from the retina to the brain. Here, we aimed to study how deeply CO is involved in regulating the expression of Period2 gene (PER2), one of the genes maintaining the intrinsic biological clock.
  • 627
  • 05 Aug 2021
Topic Review
Extracellular Vesicles Regulate Wnt Signaling in Hepatocellular Carcinoma
So far, extracellular vesicles (EVs) have played an important role in the progression of multiple cancers by regulating the Wnt pathway. The regulation of Wnt signaling by Evs in hepatocellular carcinoma (HCC) is primarily achieved by modulating the classical pathway.
  • 626
  • 24 Apr 2023
Topic Review
Epigenetics and Alzheimer’s Disease and Parkinson’s Disease
Chronic neurodegenerative disorders are believed to be caused by a combination of multiple events that damage neuronal function. Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and Parkinson’s disease (PD) is the second-most common neurodegenerative disorder worldwide. Epigenetics is defined as the stable inheritance of a phenotype, resulting from changes in the chromosomal DNA without mutations in the nucleotide sequence. A number of epigenetic research has revealed that the modification of histones accompanied by both a local and global remodeling of the chromatin structure and alternations in the transcriptional patterns are closely associated with the pathogenesis of neurodegenerative diseases, including AD and PD. 
  • 626
  • 06 Sep 2023
Topic Review
Role of Selenium in Redox Biology
Living organisms use selenium mainly in the form of selenocysteine in the active site of oxidoreductases. Here, selenium’s unique chemistry is believed to modulate the reaction mechanism and enhance the catalytic efficiency of specific enzymes in ways not achievable with a sulfur-containing cysteine. However, despite the fact that selenium/sulfur have different physicochemical properties, several selenoproteins have fully functional cysteine-containing homologues and some organisms do not use selenocysteine at all. 
  • 626
  • 29 Dec 2023
Topic Review
Mapping the Protein Kinome
The kinome includes over 500 different protein kinases, which form an integrated kinase network that regulates cellular phosphorylation signals. The kinome plays a central role in almost every cellular process and has strong linkages with many diseases. Thus, the evaluation of the cellular kinome in the physiological environment is essential to understand biological processes, disease development, and to target therapy. A number of strategies for kinome analysis have been developed, which are based on monitoring the phosphorylation of kinases or substrates. They have enabled researchers to tackle increasingly complex biological problems and pathological processes, and have promoted the development of kinase inhibitors. Additionally, with the increasing interest in how kinases participate in biological processes at spatial scales, it has become urgent to develop tools to estimate spatial kinome activity. With multidisciplinary efforts, a growing number of novel approaches have the potential to be applied to spatial kinome analysis. 
  • 625
  • 26 Apr 2023
Topic Review
PTEN-p53-AKT-MDM2 Loop in Mesenchymal Stem/Stromal Cells Regulation
Mesenchymal stromal/stem cells (MSCs) are multipotent cells that can differentiate to various specialized cells, which have the potential capacity to differentiate properly and accelerate recovery in damaged sites of the body. This stem cell technology has become the fundamental element in regenerative medicine. As reactive oxygen species (ROS) have been reported to adversely influence stem cell properties, it is imperative to attenuate the extent of ROS to the promising protective approach with MSCs’ regenerative therapy. Oxidative stress also affects the culture expansion and longevity of MSCs. Therefore, there is great need to identify a method to prevent oxidative stress and replicative senescence in MSCs. Phosphatase and tensin homologue deleted on chromosome 10/Protein kinase B, PKB (PTEN/AKT) and the tumor suppressor p53 pathway have been proven to play a pivotal role in regulating cell apoptosis by regulating the oxidative stress and/or ROS quenching.
  • 625
  • 08 Sep 2023
Topic Review
Matrix Vesicles and Media Vesicles
Mineralization-competent cells, including hypertrophic chondrocytes, mature osteoblasts, and osteogenic-differentiated smooth muscle cells secrete media extracellular vesicles (media vesicles) and extracellular vesicles bound to the extracellular matrix (matrix vesicles). Media vesicles are purified directly from the extracellular medium. On the other hand, matrix vesicles are purified after discarding the extracellular medium and subjecting the cells embedded in the extracellular matrix or bone or cartilage tissues to an enzymatic treatment. 
  • 625
  • 04 Jan 2024
Topic Review
Yin and Yang of IκB Kinases in Cancer
IκB kinases (IKKs), specifically IKKα and IKKβ, have long been recognized for their pivotal role in the NF-κB pathway, orchestrating immune and inflammatory responses.
  • 624
  • 03 Jan 2024
Topic Review
Application of μPADs in Detection of Cancer Biomarkers
Microfluidics is very crucial in lab-on-a-chip systems for carrying out operations in a large-scale laboratory environment on a single chip. Microfluidic systems are miniaturized devices in which the fluid behavior and control can be manipulated on a small platform, with surface forces on the platform being greater than volumetric forces depending on the test method used. Paper-based microfluidic analytical devices (μPADs) have been developed to be used in point-of-care (POC) technologies. μPADs have numerous advantages, including ease of use, low cost, capillary action liquid transfer without the need for power, the ability to store reagents in active form in the fiber network, and the capability to perform multiple tests using various measurement techniques. These benefits are critical in the advancement of paper-based microfluidics in the fields of disease diagnosis, drug application, and environment and food safety. Cancer is one of the most critical diseases for early detection all around the world. Detecting cancer-specific biomarkers provides significant data for both early diagnosis and controlling the disease progression. μPADs for cancer biomarker detection hold great promise for improving cure rates, quality of life, and minimizing treatment costs. 
  • 623
  • 06 Apr 2023
Topic Review
Continuum of Protein Structures and Dynamics for Function
The range of protein conformational dynamics in nature can be roughly classified into four general categories of increasing complexity and thus difficulty for characterization and prediction. The simplest case is local conformational dynamics within a largely well-defined native fold. Such dynamics include atomic thermal fluctuations around the native structure, which measure the local rigidity.
  • 623
  • 15 Jun 2023
Topic Review
IQGAPs
IQ motif-containing GTPase-activating proteins (IQGAPs) modulate a wide range of cellular processes by acting as scaffolds and driving protein components into distinct signaling networks. Their functional states have been proposed to be controlled by members of the RHO family of GTPases, among other regulators. In this study, we show that IQGAP1 and IQGAP2 can associate with CDC42 and RAC1-like proteins but not with RIF, RHOD, or RHO-like proteins, including RHOA. This seems to be based on the distribution of charged surface residues, which varies significantly among RHO GTPases despite their high sequence homology. Although effector proteins bind first to the highly flexible switch regions of RHO GTPases, additional contacts outside are required for effector activation. Sequence alignment and structural, mutational, and competitive biochemical analyses revealed that RHO GTPases possess paralog-specific residues outside the two highly conserved switch regions that essentially determine the selectivity of RHO GTPase binding to IQGAPs. Amino acid substitution of these specific residues in RHOA to the corresponding residues in RAC1 resulted in RHOA association with IQGAP1. Thus, electrostatics most likely plays a decisive role in these interactions
  • 622
  • 01 Dec 2021
Topic Review
Caenorhabditis elegans Models Established for Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease characterised by the selective and gradual loss of motor neurons in the spinal, bulbar and cortical regions. C. elegans has established itself as a favoured model organism in the field of neurodegenerative disease research. Through analysis of gene mutations pertinent to these disease, it provides a unique opportunity to identify pathogenic molecular pathways and explore promising therapeutic options. 
  • 621
  • 10 Jan 2024
Topic Review
Neuroprotective Action of Humanin and Humanin Analogues
Humanin is a 24-mer peptide first reported in the early 2000s as a new neuroprotective/cytoprotective factor rescuing neuronal cells from death induced by various Alzheimer’s disease-associated insults. Nowadays it is known that humanin belongs to the novel class of the so-called mitochondrial-derived peptides (which are encoded by mitochondrial DNA) and has been shown to exert beneficial cytoprotective effects in a series of in vitro and/or in vivo experimental models of human diseases, including not only neurodegenerative disorders but other human diseases as well (e.g., age-related macular degeneration, cardiovascular diseases, or diabetes mellitus).
  • 620
  • 08 Jan 2024
Topic Review
Melatonin Use for Early Life Origins of Hypertension
 Hypertension represents a major disease burden worldwide. Abundant evidence suggests that hypertension can originate in early life. Adverse programming processes can be prevented by early life intervention—namely, reprogramming—to avoid developing chronic diseases later in life. Melatonin is an endogenously produced hormone with a multifaceted biological function. Although melatonin supplementation has shown benefits for human health, less attention has been paid to exploring its reprogramming effects on the early life origins of hypertension.
  • 618
  • 12 May 2022
Topic Review
Ribosomal Protein uS5 and Friends
Ribosomal proteins are fundamental components of the ribosomes in all living cells. The ribosomal protein uS5 (Rps2) is a stable component of the small ribosomal subunit within all three domains of life. In addition to its interactions with proximal ribosomal proteins and rRNA inside the ribosome, uS5 has a surprisingly complex network of evolutionarily conserved non-ribosome-associated proteins.
  • 618
  • 24 May 2023
Topic Review
Molecular Biology of Miscanthus
Miscanthus is a perennial wild plant that is vital for the production of paper and roofing, as well as horticulture and the development of new high-yielding crops in temperate climates. Chromosome-level assembly of the ancient tetraploid genome of miscanthus chromosomes is reported to provide resources that can link its chromosomes to related diploid sorghum and complex polyploid sugarcane. 
  • 618
  • 25 Aug 2023
Topic Review
Long Non-Coding RNAs in Neurodegenerative Diseases
Long non-coding RNAs (lncRNAs) are novel genetic biomarkers that can be used as exclusionary tools specific to Neurodegenerative diseases (NDDs). These historical biomarkers have been there for years, so a change in the approach is necessary to better diagnose and treat these NDDs.
  • 618
  • 18 Mar 2024
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