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Topic Review
ClpB's Function in Bacterial Virulence
The molecular chaperone ClpB belongs to the Hsp100/Clp subfamily of the AAA+ ATPases. It has been established that ClpB disaggregates and reactivates aggregated cellular proteins. It has been postulated that ClpB’s protein disaggregation activity supports the survival of pathogenic bacteria under host-induced stresses (e.g., high temperature and oxidative stress), which allows them to rapidly adapt to the human host and establish infection. Interestingly, ClpB may also perform other functions in pathogenic bacteria, which are required for their virulence. Since ClpB is not found in human cells, this chaperone emerges as an attractive target for novel antimicrobial therapies in combating bacterial infections. 
  • 985
  • 11 Jun 2021
Topic Review
Bilayer Lipid Membranes in Ion Channel Functions Analysis
The bilayer lipid membrane (BLM) is the main structural component of cell membranes, in which various membrane proteins are embedded. Artificially formed BLMs have been used as a platform in studies of the functions of membrane proteins, including various ion channels. 
  • 985
  • 26 Oct 2022
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.
  • 984
  • 28 Apr 2021
Topic Review
Membrane Disruption Properties of EOs
Essential oils (EOs) is new possible weapons to fight antimicrobial resistance due to their inherent antimicrobial properties. However, the potential pharmaceutical use of EOs is confronted by several limitations, including being non-specific in terms of drug targeting, possessing a high cytotoxicity as well as posing a high risk for causing skin irritation.
  • 983
  • 22 Apr 2021
Topic Review
Mammalian Unfolded Protein Response Transducers
The unfolded protein response (UPR) bears an evolutionary conserved, dual sensitivity to both protein-folding imbalances in the endoplasmic reticulum (ER) lumen and aberrant compositions of the ER membrane, referred to as lipid bilayer stress (LBS). Through transcriptional and non-transcriptional mechanisms, the UPR upregulates the protein folding capacity of the ER and balances the production of proteins and lipids to maintain a functional secretory pathway.
  • 983
  • 03 Nov 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.
  • 983
  • 18 May 2022
Topic Review
Targeting of Signaling Pathways by Thymoquinone in Cancer
Thymoquinone is isolated from Nigella sativa with a molecular weight of 164.2 g/mol. A series of cutting-edge research works have demonstrated the health-promoting and disease-ameliorating roles of thymoquinone.
  • 983
  • 13 Jun 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.
  • 982
  • 14 Jul 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. 
  • 982
  • 13 Jan 2023
Topic Review
Estrogen Receptors in bone
Estrogens are key regulators of bone turnover in both females and males. These hormones play a major role in longitudinal and width growth throughout puberty as well as in the regulation of bone turnover. Effects of estrogens on bone involve either estrogen receptor alpha (ERα) or beta (ERβ) depending on the type of bone (femur, vertebrae, tibia, mandible), the compartment (trabecular or cortical), cell types involved (osteoclasts, osteoblasts and osteocytes) and the sex.  
  • 981
  • 18 Mar 2021
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.
  • 981
  • 10 Jun 2021
Topic Review
Development of Phosphodiesterase–Protein-Kinase Complexes
Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (protein kinases, PKs) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PKs generates an expanded active site that enhances PDE activity. This facilitates signalosome-associated PDEs to preferentially catalyze active hydrolysis of cyclic nucleotides bound to PKs and aid in signal termination. PDEs are important drug targets, and current strategies for inhibitor discovery are based entirely on targeting conserved PDE catalytic domains. This often results in inhibitors with cross-reactivity amongst closely related PDEs and attendant unwanted side effects. 
  • 981
  • 22 Jun 2021
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. 
  • 981
  • 30 Nov 2022
Topic Review
Targeting Nrf2 and NF-κB Signaling Pathways in Cancer
Plant secondary metabolites, known as phytochemicals, have gained much attention in light of the “circular economy”, to reutilize waste products deriving from agriculture and food industry. Phytochemicals are known for their onco-preventive and chemoprotective effects, among several other beneficial properties. Apple phytochemicals have been extensively studied for their effectiveness in a wide range of diseases, cancer included.
  • 981
  • 15 Feb 2023
Topic Review
Proteomics in Management of Acute Kidney Injury
Acute Kidney Injury (AKI) is currently recognized as a life-threatening disease, leading to an exponential increase in morbidity and mortality worldwide. At present, AKI is characterized by a significant increase in serum creatinine (SCr) levels, typically followed by a sudden drop in glomerulus filtration rate (GFR). Changes in urine output are usually associated with the renal inability to excrete urea and other nitrogenous waste products, causing extracellular volume and electrolyte imbalances. Several molecular mechanisms were proposed to be affiliated with AKI development and progression, ultimately involving renal epithelium tubular cell-cycle arrest, inflammation, mitochondrial dysfunction, the inability to recover and regenerate proximal tubules, and impaired endothelial function. Diagnosis and prognosis using state-of-the-art clinical markers are often late and provide poor outcomes at disease onset. Inappropriate clinical assessment is a strong disease contributor, actively driving progression towards end stage renal disease (ESRD). Proteins, as the main functional and structural unit of the cell, provide the opportunity to monitor the disease on a molecular level. Changes in the proteomic profiles are pivotal for the expression of molecular pathways and disease pathogenesis. Introduction of highly-sensitive and innovative technology enabled the discovery of novel biomarkers for improved risk stratification, better and more cost-effective medical care for the ill patients and advanced personalized medicine.
  • 981
  • 04 Sep 2023
Topic Review
Bulk purification of RNA–Protein Complexes
The ribonome interconnects the proteome and the transcriptome. Specific biology is situated at this interface, which can be studied in bulk using omics approaches. In this entry, we focus on both RNA- and ribonucleoprotein-(RNP) centric methods. These methods can be used to study the dynamics of the ribonome in response to a stimulus. The purpose of this entry is to provide and discuss an overview of the currently available RNA- and RNP-centric approaches to study RNPs. 
  • 980
  • 19 Aug 2020
Topic Review
CFTR Lifecycle Map
Cystic Fibrosis (CF) is one of the most common genetic diseases prevalent among the Caucasian population and is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To date, several hundred disease-causing mutations are known, resulting in a vast range of geno- and phenotypes, which makes the development of therapeutics especially challenging. To support the development of novel therapeutics, systems biological disease maps can be used. Disease maps represent existing knowledge on disease mechanisms in a computationally readable and comprehensive manner so they can then be used by clinicians and experimental scientists as well as computational scientists for different purposes, such as structuring high-throughput data, identifying disease biomarkers, developing better diagnostics and also identifying potential drug targets and drug repositioning. The CFTR Lifecycle Map in particular details the biogenesis of CFTR in cells to support ongoing drug discovery endeavours in CF research.
  • 980
  • 22 Nov 2021
Topic Review
Pubertal Mammary Gland
The mammary gland is a compound, branched tubuloalveolar structure and a major characteristic of mammals. The mammary gland has evolved from epidermal apocrine glands, the skin glands as an accessory reproductive organ to support postnatal survival of offspring by producing milk as a source of nutrition. The mammary gland development begins during embryogenesis as a rudimentary structure that grows into an elementary branched ductal tree and is embedded in one end of a larger mammary fat pad at birth. At the onset of ovarian function at puberty, the rudimentary ductal system undergoes dramatic morphogenetic change with ductal elongation and branching. During pregnancy, the alveolar differentiation and tertiary branching are completed, and during lactation, the mature milk-producing glands eventually develop. The early stages of mammary development are hormonal independent, whereas during puberty and pregnancy, mammary gland development is hormonal dependent.
  • 980
  • 18 Apr 2022
Topic Review
Mesenchymal Stem Cell Viral Infection and Host Responses
Mesenchymal stem cells (MSCs) play a critical role in response to stress such as infection. They initiate the removal of cell debris, exert major immunoregulatory activities, control pathogens, and lead to a remodeling/scarring phase. Interestingly, many viruses and particularly those associated to chronic infection and inflammation may hijack and polarize MSC’s immune regulatory activities to their own advantages. Virus will remain in the MSC perivascular niche while being protected from immune attack. In the context of immunodepression (e.g. organ transplantation) the hidden viruses may rebound and causing tissue injuries. 
  • 980
  • 01 Aug 2022
Topic Review
RNA Interference Past and Future Applications in Plants
Antisense RNA was observed to elicit plant disease resistance and post-translational gene silencing (PTGS). The universal mechanism of RNA interference (RNAi) was shown to be induced by double-stranded RNA (dsRNA), an intermediate produced during virus replication. Plant viruses with a single-stranded positive-sense RNA genome have been instrumental in the discovery and characterization of systemic RNA silencing and suppression.  Application of exogenously applied dsRNA is proving to be a potent strategy for delivery to improve crop performance.
  • 980
  • 29 Jun 2023
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