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Topic Review
Vegetables on the Modulation of Platelet Function
Cardiovascular diseases (CVDs) are a primary cause of deaths worldwide. Thrombotic diseases, specifically stroke and coronary heart diseases, account for around 85% of CVDs-induced deaths. Platelets (small circulating blood cells) are responsible for the prevention of excessive bleeding upon vascular injury, through blood clotting (haemostasis). However, their unnecessary activation results in thrombotic diseases. Hence, it is critical to control platelet activation under pathological conditions. Regular diet has a strong relationship with the development of CVDs, and therefore reviewing their beneficial effects on the modulation of platelet function is essential.  Here,  a few important, regularly used vegetables and demonstrate their effects on the modulation of platelet activation are listed.  
  • 810
  • 29 Mar 2022
Topic Review
Therapeutic Strategies for Leukemic Stem Cells
Notoriously known for their capacity to reconstitute hematological malignancies in vivo, leukemic stem cells (LSCs) represent key drivers of therapeutic resistance and disease relapse, posing as a major medical dilemma. Despite having low abundance in the bulk leukemic population, LSCs have developed unique molecular dependencies and intricate signaling networks to enable self-renewal, quiescence, and drug resistance. The abundance of molecular and phenotypical aberrations associated with LSCs offers a wealth of promising therapeutic targets. Therapeutic designs have focused on drugging surface biomarkers selectively overexpressed on LSCs, antagonizing the protective bone marrow (BM) microenvironment niche to dismantle LSC dormancy, blocking signal transduction to re-sensitize resistant LSCs to available chemotherapeutics, and even expediting the drug supply pipeline through drug repurposing. Evidently, growing insight into the biological properties and prognostic values of LSCs have prompted the implementation of many clinical trials and have laid critical groundwork for the development of more effective, personalized, scalable, and less-toxic therapeutic strategies.
  • 810
  • 08 Oct 2022
Topic Review
Extracellular ncRNAs
Non-coding RNAs (ncRNAs) are key regulators of post-transcriptional gene expression in prokaryotic and eukaryotic organisms. These molecules can interact with mRNAs or proteins, affecting a variety of cellular functions. Emerging evidence shows that intra/inter-species and trans-kingdom regulation can also be achieved with exogenous RNAs, which are exported to the extracellular medium, mainly through vesicles. In bacteria, membrane vesicles (MVs) seem to be the more common way of extracellular communication.
  • 809
  • 06 Jan 2021
Topic Review
Epstein-Barr Virus Lytic Genes in Carcinogenesis
Epstein-Barr virus (EBV) was the first human tumor virus to be discovered and is a causative agent for several cancer types of epithelial and lymphoid origin. EBV has two life cycles comprised of latent and lytic phases. The lytic cycle is when new virions are produced, whereas the latent cycle is a state of persistent infection without productive viral replication. It has been recognized that latent infection is the predominant mode of infection in EBV-associated cancers and the expression of a restricted set of latent genes drives disease development. 
  • 809
  • 15 Dec 2022
Topic Review
Modelling Ischaemic Stroke In Vitro
Most of the knowledge on the pathophysiological mechanisms of an ischaemic stroke is derived from animal-based in vitro and in vivo models. Over the past decades, different animal models of stroke have been developed, induced by emboli, intraluminal suture, photothrombosis or endothelin-1, typically in rodents. The rat is one of the most commonly used species in stroke research, among other reasons, due to the similarity of the cerebral vasculature and physiology with that of humans. Moreover, mice are often used, since they are helpful in unravelling the function of certain genes in the pathophysiology of stroke by means of the creation of transgenic mice. Animal stroke models have been an indispensable tool, as they can model different aspects of the complex pathophysiology of ischaemic stroke that cannot be modelled (yet) in simple in vitro models lacking intact blood vessels and blood flow. However, simplified, highly controlled in vitro systems are required and preferred when investigating specific basic mechanisms and cell type-specific responses under ischaemia-like conditions. Besides, in the context of testing potential neuroprotective compounds, working in vitro allows high-throughput screenings, even on a human-based background.
  • 808
  • 19 Jul 2022
Topic Review
Glucose-Induced Mitochondrial Dysfunction in Diabetic Kidney Disease
The kidney is one of the most energy-demanding organs and, after the heart, has the second highest expression of proteins involved in mitochondrial function and oxygen consumption. The kidney requires energy mainly for solute reabsorption, among other tasks including waste removal, maintenance of electrolyte and fluid balance and acid–base homeostasis. The generation of an ion gradient across the plasma membrane by Na+/K+-ATPase is essential for solute reabsorption. Therefore, mitochondrial dysfunction is postulated to play a central role in the pathogenesis and progression of kidney diseases including DKD. Mitochondrial dysfunction plays an important role in the pathogenesis and progression of diabetic kidney disease (DKD).
  • 808
  • 02 Mar 2022
Topic Review
Immune Checkpoint Molecules
Antibodies against inhibitory immune checkpoint molecules (ICPMs), referred to as immune checkpoint inhibitors (ICIs), have gained a prominent place in cancer therapy. Several ICIs in clinical use have been engineered to be devoid of effector functions because of the fear that ICIs with preserved effector functions could deplete immune cells, thereby curtailing antitumor immune responses. ICPM ligands (ICPMLs), however, are often overexpressed on a sizeable fraction of tumor cells of many tumor types and these tumor cells display an aggressive phenotype with changes typical of tumor cells undergoing an epithelial-mesenchymal transition. Moreover, immune cells expressing ICPMLs are often endowed with immunosuppressive or immune-deviated functionalities. Taken together, these observations suggest that compounds with the potential of depleting cells expressing ICPMLs may become useful tools for tumor therapy.
  • 807
  • 28 Apr 2021
Topic Review
Krüppel-like Factors 4 and 5 in Colorectal Tumorigenesis
Krüppel-like factors (KLFs) are transcription factors regulating various biological processes such as proliferation, differentiation, migration, invasion, and homeostasis. Importantly, they participate in disease development and progression. KLFs are expressed in multiple tissues, and their role is tissue- and context-dependent. KLF4 and KLF5 are two fascinating members of this family that regulate crucial stages of cellular identity from embryogenesis through differentiation and, finally, during tumorigenesis. They maintain homeostasis of various tissues and regulate inflammation, response to injury, regeneration, and development and progression of multiple cancers such as colorectal, breast, ovarian, pancreatic, lung, and prostate, to name a few.
  • 806
  • 12 Sep 2023
Topic Review
Molecular Mediators of RNA Loading into Extracellular Vesicles
Extracellular vesicles (EVs) are a family of membrane-coated vesicles with different proteomic and lipidomic profile, as well as different size. An increasing number of studies have demonstrated that non-coding RNA (ncRNAs) cooperate in the gene regulatory networks with other biomolecules, including coding RNAs, DNAs and proteins. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in transcriptional and translation regulation at different levels. Intriguingly, ncRNAs can be packed in vesicles, released in the extracellular space, and finally internalized by receiving cells, thus affecting gene expression also at distance. 
  • 805
  • 15 Dec 2021
Topic Review
NRF2 and Key Transcriptional Targets
Melanocytes are dendritic, pigment-producing cells located in the skin and are responsible for its protection against the deleterious effects of solar ultraviolet radiation (UVR), which include DNA damage and elevated reactive oxygen species (ROS). They do so by synthesizing photoprotective melanin pigments and distributing them to adjacent skin cells (e.g., keratinocytes). However, melanocytes encounter a large burden of oxidative stress during this process, due to both exogenous and endogenous sources.To protect themselves, they utilize numerous antioxidant systems to reduce the amount of reactive oxygen and nitrogen species present in the cell and this activity then contributes towards the prevention of cancer formation. However, after the formation of melanoma these same antioxidant systems are often coopted by the cancer in order to promote its uncontrolled growth and metastasis.
  • 805
  • 06 Apr 2022
Topic Review
Potential Causal Contributions to Post-Traumatic Syndrome
In vitro models of traumatic brain injury (TBI) help to elucidate the pathological mechanisms responsible for cell dysfunction and death.  Mitochondrial Ca2+ overload and a drop in ΔΨm may cause delayed neuronal death and thus play a key role in the development of the post-traumatic syndrome. Preventing prolonged ΔΨm depolarization may be a promising therapeutic approach to improve neuronal survival after traumatic brain injury. 
  • 804
  • 06 Apr 2022
Topic Review
Role of Extracellular Vesicles in Hematological Malignancies
The tumor microenvironment (TME) plays an important role in the development and progression of hematological malignancies. In addition to several factors, such as growth factors, cytokines, extracellular matrix (ECM) molecules, etc., a growing body of evidence has indicated that extracellular vesicles (EVs) play a crucial role in the communication of tumor cells within the TME, thereby contributing to the pathogenesis of hematological malignancies. 
  • 804
  • 13 Jun 2023
Topic Review
AtWAKL10
Receptor-like kinases (RLKs) constitute a large group of cell surface receptors that play crucial roles in multiple biological processes. However, the function of most RLKs in plants has not been extensively explored, and much less for the class of cell wall associated kinases (WAKs) and WAK-like kinases (WAKLs). In this study, analyses of developmental expression patterns uncovered a putative role of AtWAKL10 in modulating leaf senescence, which was further investigated at physiological and molecular levels. The expression level of AtWAKL10 increased with the developmental progression and was rapidly upregulated in senescing leaf tissues. The promoter of AtWAKL10 contains various defense and hormone responsive elements, and its expression could be significantly induced by exogenous ABA, JA and SA. Moreover, the loss-of-function atwakl10 mutant showed earlier senescence along the course of natural development and accelerated leaf senescence under darkness and hormonal stresses, while plants overexpressing AtWAKL10 showed an opposite trend.
  • 803
  • 18 May 2021
Topic Review
Secreted Frizzled-Related Protein 1
Secreted frizzled-related protein 1 (SFRP1) encodes one of the eight known SFRP family members. This 3873 base pair coding gene is localized on chromosome 8p11, from nucleotide 41,261,957 to 41,309,473.
  • 803
  • 20 May 2021
Topic Review
Extracellular Vesicles as Novel Treatments
Mesenchymal stem/stromal cells (MSCs) represent a promising therapy for musculoskeletal diseases. There is compelling evidence indicating that MSC effects are mainly mediated by paracrine mechanisms and in particular by the secretion of extracellular vesicles (EVs). Many studies have thus suggested that EVs may be an alternative to cell therapy with MSCs in tissue repair.
  • 803
  • 14 Oct 2021
Topic Review
Intratumor Heterogeneity in Hepatocellular Carcinoma: Challenges and Opportunities
Hepatocellular carcinoma (HCC) represents a leading cause of cancer-related death, but it remains difficult to treat. Intratumor genetic and phenotypic heterogeneity are inherent properties of breast, skin, lung, prostate, and brain tumors, and intratumor heterogeneity (ITH) helps define prognosis and therapeutic response in these cancers. Several recent studies estimate that ITH is inherent to HCC and attribute the clinical intractability of HCC to this heterogeneity.
  • 803
  • 25 Nov 2021
Topic Review
MiRNAs/lncRNAs/circRNAs in Redox Control of Cell Senescence
Cell senescence is critical in diverse aspects of organism life. It represents a physiological program to arrest proliferation of damaged/harmful cells and is now considered an important contributor in aging and age-related pathologies. Non-coding RNAs are endogenous transcripts that govern gene regulatory networks impacting both physiological and pathological events. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and more recently circular RNAs (circRNAs) are considered crucial regulators of almost all cellular processes, including responses evoked by oxidative stress, such as senescence. 
  • 803
  • 15 Apr 2022
Topic Review
Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neurodegenerative disease. Cell damage in ALS is the result of many different, largely unknown, pathogenetic mechanisms. Superoxide Dismutase 1 (SOD1) physiologically mediates intracellular peroxide generation. About 10% of ALS subjects show a familial disease associated with different gain-of-function SOD1 mutations. The occurrence of sporadic ALS, not clearly associated with SOD1 defects, has been also described. SOD1-dependent pathways have been involved in neuron functional network as well as in immune-response regulation. 
  • 800
  • 30 Nov 2023
Topic Review
Immune System, Inflammation and Autoantigens in wAMD
Wet age-related macular degeneration (wAMD) is a chronic inflammation-associated neurodegenerative disease affecting the posterior part of the eye in the aging population. Aging results in the reduced functionality of cells and tissues, including the cells of the retina. Initiators of a chronic inflammatory and pathologic state in wAMD may be a result of the accumulation of inevitable metabolic injuries associated with the maintenance of tissue homeostasis from a young age to over 50. Apart from this, risk factors like smoking, genetic predisposition, and failure to repair the injuries that occur, alongside attempts to rescue the hypoxic outer retina may also contribute to the pathogenesis. Aging of the immune system (immunosenescence) and a compromised outer blood retinal barrier (BRB) result in the exposure of the privileged milieu of the retina to the systemic immune system, further increasing the severity of the disease. 
  • 800
  • 12 Dec 2023
Topic Review
P27Kip1
The Cyclin-dependent kinase (CDK) regulator p27Kip1 is a gatekeeper of G1/S transition. It also regulates G2/M progression and cytokinesis completion, via CDK-dependent or -independent mechanisms. Recently, other important p27Kip1 functions have been described, including the regulation of cell motility and migration, the control of cell differentiation program and the activation of apoptosis/autophagy.
  • 800
  • 13 Sep 2021
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