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Topic Review
Polymyxin B Immobilized Fiber Column
Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.
  • 876
  • 10 Mar 2021
Topic Review
ABCC6 Transporter in Hepatic Cells
Pseudoxanthoma elasticum (PXE) is a complex autosomal recessive disease caused by mutations of ABCC6 transporter and characterized by ectopic mineralization of soft connective tissues.
  • 876
  • 20 May 2021
Topic Review
Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide
One of the main targets of NO in cells is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is due to the presence of a highly reactive cysteine residue in the active center of this protein, as well as to the high content of this protein in all cells. The main products of GAPDH modification with nitric oxide are S-nitrosylated GAPDH and S-sulfenated GAPDH (GAPDH-SNO and GAPDH-SOH, respectively). Modification of GAPDH with nitric oxide is of particular interest due to the fact that it causes the accumulation of GAPDH in the nucleus and induction of apoptosis. According to the most popular hypothesis, a wide range of apoptotic stimuli augment NO production in the cells, GAPDH is nitrosylated by NO, which leads to inactivation of the protein and to conformational changes in its molecule. These alterations facilitate the binding of GAPDH with the E3-ubiquitin-ligase Siah1. Siah1, which possesses a nuclear localization signal (NLS), translocates GAPDH to the nucleus and stimulates a cascade of apoptotic reactions. However, the molecular mechanisms of this signaling pathway have not yet been studied in detail. There are no direct data on the selective interaction of the S-nitrosylated GAPDH with Siah1. It cannot be excluded that any modifications of the catalytic cysteine residue, which are accompanied by a weakening of interactions between the enzyme and NAD+, lead to a change in the conformation of GAPDH, and stimulate its binding to some partner proteins—in particular, Siah1.
  • 876
  • 03 Dec 2021
Topic Review
Muscle Glycogen Phosphorylase
Glycogen phosphorylase (PG) is a key enzyme taking part in the first step of glycogenolysis. Muscle glycogen phosphorylase (PYGM) differs from other PG isoforms in expression pattern and biochemical properties. The main role of PYGM is providing sufficient energy for muscle contraction. 
  • 875
  • 19 May 2021
Topic Review
L-Type Ca2+ Channel Regulation by Calmodulin and CaBP1
L-type voltage-gated Ca2+ channels (CaV1.2 and CaV1.3, called CaV) interact with the Ca2+ sensor proteins, calmodulin (CaM) and Ca2+ binding Protein 1 (CaBP1), that oppositely control Ca2+-dependent channel activity. CaM and CaBP1 can each bind to the IQ-motif within the C-terminal cytosolic domain of CaV, which promotes increased channel open probability under basal conditions. At elevated cytosolic Ca2+ levels (caused by CaV channel opening), Ca2+-bound CaM binding to CaV is essential for promoting rapid Ca2+-dependent channel inactivation (CDI). By contrast, CaV binding to CaBP1 prevents CDI and promotes Ca2+-induced channel opening (called CDF). 
  • 874
  • 15 Dec 2021
Topic Review
Health Benefits of Curcumin
Curcumin is the principal curcuminoid found in the rhizomes of turmeric. Due to its therapeutic action against cancer, depression, diabetes, some bacteria, and oxidative stress, it has been used widely in medicine since ancient times.
  • 874
  • 24 May 2023
Topic Review
C1q in Neurodegenerative Diseases
Complement Component 1q (C1q), an initiating recognition molecule of the classical complement pathway, can interact with a variety of ligands and perform a range of functions in physiological and pathophysiological conditions of the central nervous system (CNS). Beyond its established roles in CNS growth, development, and bodily immunization, a novel facet of C1q’s functionality has been freshly unveiled within the intricate tapestry of neuropathological pathways that underpin neurodegenerative disorders and traumatic brain injury (TBI). This revelation has cast a spotlight on C1q as a prospective therapeutic avenue for safeguarding neuronal well-being or for retarding the progression of neurodegenerative maladies.
  • 874
  • 13 Oct 2023
Topic Review
Diabetic Complications
Diabetes is the cause of several macrovascular and microvascular complications. Macrovascular complications associated with diabetes include atherosclerosis and stroke; and microvascular complications include diabetic retinopathy, nephropathy, and neuropathy. Due to the progressive nature of diabetes, diabetes vascular complications causes the majority of the burden of diabetes with intense consequences on the anatomy, structure, and function of several cells, tissues, and organs, and consequently on the patient’s well-being.
  • 873
  • 12 Jan 2023
Topic Review
[GADV]-amino Acids and GNC Codons Selected
The genetic code connecting gene with protein is one of the six members (gene, tRNA, genetic code, protein, metabolism, and cell structure) composing the fundamental life system, including the core life system (gene, tRNA, genetic code, and protein). Revealing the origin of the genetic code, one of four members of the core life system might lead to solving the mystery of the origin of life. Therefore, it is quite important to clarify how amino acids and codons were selected among messy organic compounds on primitive Earth and how the first genetic code was established.
  • 873
  • 15 Feb 2023
Topic Review
General Characteristics and Nephroprotective Properties of Salvia Genus
The study of medicinal plants is important, as they are the natural reserve of potent biologically active compounds. With wide use in traditional medicine and the inclusion of several species (as parts and as a whole plant) in pharmacopeia, species from the genus Salvia L. are known for the broad spectrum of their biological activities. Studies suggest that these plants possess antioxidant, anti-inflammatory, antinociceptive, anticancer, antimicrobial, antidiabetic, antiangiogenic, hepatoprotective, cognitive and memory-enhancing effects. Phenolic acids, terpenoids and flavonoids are important phytochemicals, which are primarily responsible for the medicinal activity of Salvia L.
  • 873
  • 14 Dec 2023
Topic Review
FABP in α-Synuclein-Induced Mitochondrial Injury
Synucleinopathies are diverse diseases with motor and cognitive dysfunction due to progressive neuronal loss or demyelination, due to oligodendrocyte loss in the brain. While the etiology of neurodegenerative disorders (NDDs) is likely multifactorial, mitochondrial injury is one of the most vital factors in neuronal loss and oligodendrocyte dysfunction, especially in Parkinson’s disease, dementia with Lewy body, multiple system atrophy, and Krabbe disease. In recent years, the abnormal accumulation of highly neurotoxic α-synuclein in the mitochondrial membrane, which leads to mitochondrial dysfunction, was well studied. Furthermore, fatty acid-binding proteins (FABPs), which are members of a superfamily and are essential in fatty acid trafficking, were reported to trigger α-synuclein oligomerization in neurons and glial cells and to target the mitochondrial outer membrane, thereby causing mitochondrial loss.
  • 872
  • 02 Jun 2021
Topic Review
CirDNA Metabolism and Biological Role
Circulating DNA has already proven itself as a valuable tool in translational medicine. However, one of the overlooked areas of circulating DNA research is its association with different proteins, despite considerable evidence that this association might impact DNA’s fate in circulation and its biological role. The colorful history of circulating DNA (cell-free DNA and cell surface bound DNA, which hereafter will be referred to as cirDNA) research and attempts of its use in the field of oncology went from being skeptically discarded to becoming a valuable tool in clinical oncology.
  • 871
  • 22 Jul 2022
Topic Review
Extracellular Vesicles in Reproduction
Secretory extracellular vesicles (EVs) are membrane-enclosed microparticles that mediate cell to cell communication in proximity to, or distant from, the cell of origin. Extracellular vesicles mediate temporal and spatial interaction during many events in sexual reproduction and supporting embryo-maternal dialogue. Molecular characterization of EVs isolated in physiological and pathological conditions may increase our understanding of reproductive and obstetric diseases and assist the search for potential non-invasive biomarkers. Moreover, a more precise vision of the cocktail of biomolecules inside the EVs mediating communication between the embryo and mother could provide new insights to optimize the therapeutic action and safety of EV use.
  • 870
  • 20 Nov 2020
Topic Review
Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer
Long non-coding RNAs (lncRNAs) are classified as a group of transcripts that regulate various biological processes, such as RNA processing, epigenetic control, and signaling pathways. According to recent studies, lncRNAs are dysregulated in cancer and play an important role in cancer incidence and spreading. There is also an association between lncRNAs and the overexpression of some tumor-associated proteins, including carbonic anhydrases II, IX, and XII (CA II, CA IX, and CA XII). Therefore, not only CA inhibition but also lncRNA modulation, could represent an attractive strategy for cancer prevention and therapy. Experimental studies have suggested that herbal compounds regulate the expression of many lncRNAs involved in cancer, such as HOTAIR (HOX transcript antisense RNA), H19, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), PCGEM1 (Prostate cancer gene expression marker 1), PVT1, etc. These plant-derived drugs or phytochemicals include resveratrol, curcumin, genistein, quercetin, epigallocatechin-3-galate, camptothecin, and 3,3'-diindolylmethane. More comprehensive information about lncRNA modulation via phytochemicals would be helpful for the administration of new herbal derivatives in cancer therapy.
  • 870
  • 01 Dec 2021
Topic Review
Novel Heterocyclic Derivatives against SARS-CoV-2
The heterocyclic ring derivatives were evaluated for their therapeutic potentials against SARS-CoV-2 Mpro, Spro, and RdRp. All the compounds reported showed excellent binding affinities with the various target proteins. Among the derivatives, compound C13 exhibits the highest binding affinity for the drug targets Spro (−10.6 kcal/mol) and RdRp (−9.5 kcal/mol), respectively. At a binding affinity of −8.8kcal/mol, the compound C15 exhibits the highest binding affinity for Mpro. The compounds interacted with the LEU A:271, LEU A:287, ASP A:289, and LEU A:272 of Mpro and the HIS A:540, PRO A:415, PHE A:486, and LEU A:370 of the Spro receptor binding motif and some active site amino acids of RdRp. The compounds also possess a favourable ADMET profile and showed no tendency towards hERG inhibition, hepatotoxicity, carcinogenicity, mutagenicity, or drug-liver injury. 
  • 870
  • 17 Dec 2021
Topic Review
LonP1 in the Oral and Maxillofacial Regions
Recent studies have indicated a central role for LonP1 in mitochondrial function. Its physiological functions include proteolysis, acting as a molecular chaperone, binding mitochondrial DNA, and being involved in cellular respiration, cellular metabolism, and oxidative stress. Given its vital role in energy metabolism, LonP1 has been suggested to be associated with multi-system neoplasms and developmental disorders. 
  • 870
  • 21 Nov 2022
Topic Review
Dysregulated JNK Signaling Pathway in Human Diseases
JNK is named after c-Jun N-terminal kinase, as it is responsible for phosphorylating c-Jun. As a member of the mitogen-activated protein kinase (MAPK) family, JNK is also known as stress-activated kinase (SAPK) because it can be activated by extracellular stresses including growth factor, UV irradiation, and virus infection. Functionally, JNK regulates various cell behaviors such as cell differentiation, proliferation, survival, and metabolic reprogramming. Dysregulated JNK signaling contributes to several types of human diseases.
  • 870
  • 11 Mar 2024
Topic Review
Versatile Peroxiredoxin
Peroxiredoxins are multifunctional enzymes that play a key role in protecting cells from stresses and maintaining the homeostasis of many cellular processes. Peroxiredoxins are firstly identified as antioxidant enzymes that can be found in all living organisms. Later studies further explored peroxiredoxins also act as redox signaling regulators, chaperones, and pro-inflammatory factors, that play important roles in oxidative defense system, redox signaling, protein folding, cycle cell progression, DNA integrity, inflammation, and carcinogenesis. The versatility of peroxiredoxins is mainly based on their unique active center cysteine with wide range of redox states and the ability to switch between low and high molecular weight species for regulating their peroxidase and chaperone activities. Understanding molecular mechanisms of peroxiredoxin involvement in these processes will allow developing new approaches to enhance longevity and treat various cancers.
  • 869
  • 21 Jun 2022
Topic Review
Cancer-Associated Fibroblasts in Cholangiocarcinoma
Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis.
  • 869
  • 10 Nov 2022
Topic Review
Vanadium Effects on Lipid Peroxidation and Disease Processes
Lipid peroxidation (LPO), a process that affects human health, can be induced by exposure to vanadium salts and compounds. LPO is often exacerbated by oxidation stress, with some forms of vanadium providing protective effects. The LPO reaction involves the oxidation of the alkene bonds, primarily in polyunsaturated fatty acids, in a chain reaction to form radical and reactive oxygen species (ROS). The important question is which radical starts the chain first. On the one hand, a radical is needed (oxidative stress environment) while on the other hand, LPO amplifies and contributes to changing the redox state towards oxidation (what was called oxidative stress). 
  • 869
  • 31 Mar 2023
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