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Topic Review
Lipidomics
Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. 
  • 1.1K
  • 27 Apr 2021
Topic Review
Metabolic Reprogramming in Tumor Endothelial Cells
The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. 
  • 1.1K
  • 12 Oct 2022
Topic Review
ORP5 and ORP8
Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.
  • 1.1K
  • 15 Jul 2021
Topic Review
FAK Inhibition and Corneal Fibroblast Differentiation in vitro
Fibrosis is often known as a response of a tissue to injury, and since the three transforming growth factor-beta (TGF-β) isoforms (TGF-β1, -β2, and -β3) are the main regulators of cell migration, differentiation, proliferation, and gene expression, they were implicated in both reparative and fibrotic responses. All three TGF-β isoforms are homologues, sharing an extensive similarity in their amino acid sequences (80%), which may result in overlapping functions (i.e., SMAD-dependent signaling, modulating inflammatory responses); however, subtle differences in the sequences exist, thus potentially eliciting opposing effects. For example, several studies showed that TGF-β1 and -β2 are factors that drive the formation of fibrosis in corneal scarring models [8,9,10], whereas TGF-β3 was reported to downregulate fibrosis and promote scarless wound healing (healing without fibrosis).
  • 1.1K
  • 29 Mar 2022
Topic Review
Trans-Synaptic Neurexin–Neuroligin Interaction
Synapses serve as the interface for the transmission of information between neurons in the central nervous system. The structural and functional characteristics of synapses are highly dynamic, exhibiting extensive plasticity that is shaped by neural activity and regulated primarily by trans-synaptic cell-adhesion molecules (CAMs). Prototypical trans-synaptic CAMs, such as neurexins (Nrxs) and neuroligins (Nlgs), directly regulate the assembly of presynaptic and postsynaptic molecules, including synaptic vesicles, active zone proteins, and receptors. Therefore, the trans-synaptic adhesion mechanisms mediated by Nrx–Nlg interaction can contribute to a range of synaptopathies in the context of pathological pain and other neurological disorders.
  • 1.1K
  • 01 Jul 2022
Topic Review
Extracellular Vesicles and Immune Function
Extracellular vesicles (EVs) are cargo of proteins, nucleic acids, and lipids produced by eukaryotic and prokaryotic cells both under physiological and pathological conditions. They are found in virtually all body fluids such as plasma, saliva, amniotic fluid, and breast milk, suggesting key roles in immune development and function at different life stages from in utero to aging. Under inflammatory conditions, plasma EV levels are increased and exacerbate immune activation and inflammatory reaction. During infection, bacteria derived EVs can also affect host immunity as pathogenic bacteria derived EVs having pro-inflammatory effects.
  • 1.1K
  • 30 Oct 2020
Topic Review
Lysophosphatidic Acid and Cancer
Lysophosphatidic acid (LPA) is a bioactive lipid mediator primarily derived from membrane phospholipids. LPA initiates cellular effects upon binding to a family of G protein-coupled receptors, termed LPA receptors (LPAR1 to LPAR6). LPA signaling drives cell migration and proliferation, cytokine production, thrombosis, fibrosis, angiogenesis, and lymphangiogenesis.
  • 1.1K
  • 14 Jul 2021
Topic Review
Oxidative Stress in Sepsis
Sepsis is the leading cause of acute kidney injury (AKI) and leads to increased morbidity and mortality in intensive care units. Current treatments for septic AKI are largely supportive and are not targeted towards its pathophysiology. Sepsis is commonly characterized by systemic inflammation and increased production of reactive oxygen species (ROS), particularly superoxide. Concomitantly released nitric oxide (NO) then reacts with superoxide, leading to the formation of reactive nitrogen species (RNS), predominantly peroxynitrite. Sepsis-induced ROS and RNS can reduce the bioavailability of NO, mediating renal microcirculatory abnormalities, localized tissue hypoxia and mitochondrial dysfunction, thereby initiating a propagating cycle of cellular injury culminating in AKI. 
  • 1.1K
  • 11 Oct 2021
Topic Review
NF-κB and Human Cancer
Transcription factor NF-κB has been extensively studied for its varied roles in cancer since its initial characterization as a potent retroviral oncogene several decades ago. It is now clear that NF-κB plays a major role in a large variety of human cancers, including especially ones of immune cell origin. NF-κB is generally constitutively or aberrantly activated in human cancers where it is involved.
  • 1.1K
  • 25 Dec 2021
Topic Review
Single-Cell Probe Force Studies
The replacement of the cantilever tip by a living cell in Atomic Force Microscopy (AFM) experiments permits the direct quantification of cell–substrate and cell–cell adhesion forces. This single-cell probe force measurement technique, when complemented by microscopy, allows controlled manipulation of the cell with defined location at the area of interest. Here, measurements aimed to characterize and compare the adhesion capacities of parental MCF7 cells and cells overexpressing the embryonic transcription factor Sox2, which have a higher capacity for invasion and are more resistant to endocrine therapy in vivo. Our findings demonstrate the strength of this approach to assess and compare the adhesion properties of cell lines and to illustrate the heterogeneity of adhesive strength found in breast cancer cells.
  • 1.1K
  • 30 Oct 2020
Topic Review
Multienzymatic Processes Involving Baeyer–Villiger Monooxygenases
Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. 
  • 1.1K
  • 11 May 2021
Topic Review
Outlook on Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) is characterized as a disorder of the heart muscle. It is distinguished by the widening/dilation of the left ventricle of the heart with left ventricular or biventricular systolic dysfunction. Contractile functioning of the left ventricle is highly compromised due to dilation. However, in some cases of DCM, the right ventricle is also dilated. Dilated cardiomyopathy (DCM) remains an enigmatic cardiovascular disease (CVD) condition characterized by contractile dysfunction of the myocardium due to dilation of the ventricles. DCM is one of the major forms of CVD contributing to heart failure. Dilation of the left or both ventricles with systolic dysfunction, not explained by known causes, is a hallmark of DCM. Progression of DCM leads to heart failure. Genetic and various other factors greatly contribute to the development of DCM, but the etiology has still remained elusive in a large number of cases. 
  • 1.1K
  • 15 Jun 2022
Topic Review
Hydrodynamically Closed Capillary Electrophoresis
Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological matrices. To address some of the challenges of Capillary Electrophoresis (CE), such as low concentration sensitivity and performance degradation linked to the adsorption and interference of matrix components, CE in a hydrodynamically closed system was evaluated using the model compounds Pindolol and Propranolol. Some established validation parameters such as repeatability of injection, efficiency, resolution and sensitivity were used to assess its performance, and it was found to be broadly identical to that of hydrodynamically opened systems. While some reduction in separation efficiency was observed, this was mainly due to dispersion caused by injection and it had no impact on the ability to resolve enantiomers of model compounds even when spiked into complex biological matrix such as blood serum. An approximately 18- to 23-fold increase in concentration sensitivity due to the employment of wide bore capillaries was observed. This brings the sensitivity of CE to a level similar to that of liquid chromatography techniques. In addition to this benefit and unlike in hydrodynamically opened systems, suppression of electroosmotic flow, which is essential for hydrodynamically closed systems practically eliminates the matrix effects that are linked to protein adsorption.
  • 1.1K
  • 29 Sep 2020
Topic Review
Natural Salicylates
Salicylic acid (SA) is a plant hormone which plays a crucial role in the plant defense against various pathogens and abiotic stresses.
  • 1.1K
  • 18 Mar 2021
Topic Review
Mitochondrial HSP70 Chaperone System
Mitochondrial HSP70 (mtHSP70/GRP75/HSPA9/PBP74), also called mortalin, is an essential protein belonging to the HSP70 sub-family which has great importance for mitochondrial biogenesis and the correct functioning of the whole cellular machinery.
  • 1.1K
  • 26 Aug 2021
Topic Review
Agri-Food Waste from Apple, Pear, and Sugar Beet
Endothelial damage is recognized as the initial step that precedes several cardiovascular diseases (CVD), such as atherosclerosis, hypertension, and coronary artery disease. It has been demonstrated that the best treatment for CVD is prevention, and, in the frame of a healthy lifestyle, the consumption of vegetables, rich in bioactive molecules, appears effective at reducing the risk of CVD. In this context, the large amount of agri-food industry waste, considered a global problem due to its environmental and economic impact, represents an unexplored source of bioactive compounds. The waste matrices of apple, pear, and sugar beet crops can represent promising starting material for producing “upcycled” products with functional applications, such as the prevention of endothelial dysfunction linked to cardiovascular diseases.
  • 1.1K
  • 22 Sep 2022
Topic Review
Vertebral Fractures in HIV-Infected Patients
HIV-infected patients show high risk of fracture. The aims of our study were to determine the prevalence of vertebral fractures (VFs) and their associations with vitamin D in HIV patients. 100 patients with HIV infection and 100 healthy age- and sex-matched controls were studied. Bone mineral density was measured by quantitative ultrasound at the non-dominant heel. Serum osteocalcin and C-terminal telopeptide of collagen type 1 served as bone turnover markers. Bone ultrasound measurements were significantly lower in patients compared with controls (Stiffness Index (SI): 80.58 ± 19.95% vs. 93.80 ± 7.10%, respectively, p < 0.001). VFs were found in 16 patients and in 2 controls. HIV patients with vertebral fractures showed lower stiffness index (SI) (70.75 ± 10.63 vs. 83.36 ± 16.19, respectively, p = 0.045) and lower vitamin D levels (16.20 ± 5.62 vs. 28.14 ± 11.94, respectively, p < 0.02). The majority of VFs (87.5%) were observed in HIV-infected patients with vitamin D insufficiency, and regression analysis showed that vitamin D insufficiency was significantly associated with vertebral fractures (OR 9.15; 95% CI 0.18–0.52, p < 0.04). VFs and are a frequent occurrence in HIV-infected patients and may be associated with vitamin D insufficiency.
  • 1.1K
  • 03 Nov 2020
Topic Review
JAK/STAT Pathway in Pulmonary Hypertension
Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular, and cellular processes involved in PH. Chronic inflammation contributes to pulmonary artery remodeling and PH, among other vascular disorders, and many inflammatory mediators signal through the JAK/STAT pathway. Recent evidence indicates that the JAK/STAT pathway is overactivated in the pulmonary arteries of patients with PH of different types. In addition, different profibrotic cytokines such as IL-6, IL-13, and IL-11 and growth factors such as PDGF, VEGF, and TGFβ1 are activators of the JAK/STAT pathway and inducers of pulmonary remodeling, thus participating in the development of PH. The understanding of the participation and modulation of the JAK/STAT pathway in PH could be an attractive strategy for developing future treatments. 
  • 1.1K
  • 19 May 2021
Topic Review
Oxidative Crosslinking of Peptides and Proteins
Covalent crosslinks within or between proteins play a key role in determining the structure and function of proteins. Some of these are formed intentionally by either enzymatic or molecular reactions and are critical to normal physiological function. Others are generated as a consequence of exposure to oxidants (radicals, excited states or two-electron species) and other endogenous or external stimuli, or as a result of the actions of a number of enzymes (e.g., oxidases and peroxidases). Increasing evidence indicates that the accumulation of unwanted crosslinks, as is seen in ageing and multiple pathologies, has adverse effects on biological function.
  • 1.1K
  • 24 Feb 2022
Topic Review
α-Mangostin Nanoparticles in Breast Cancer
α-Mangostin (AMG) is a potent anticancer xanthone that was discovered in mangosteen (Garcinia mangostana Linn.). AMG possesses the highest opportunity for chemopreventive and chemotherapeutic therapy. AMG inhibits every step in the process of carcinogenesis. AMG suppressed multiple breast cancer (BC) cell proliferation and apoptosis by decreasing the creation of cancerous compounds. Accumulating BC abnormalities and their associated molecular signaling pathways promotes novel treatment strategies. Chemotherapy is a commonly used treatment; due to the possibility of unpleasant side effects and multidrug resistance, there has been substantial progress in searching for alternative solutions, including the use of plant-derived natural chemicals. Due to the limitations of conventional cancer therapy, nanotechnology provides hope for effective and efficient cancer diagnosis and treatment. Nanotechnology enables the delivery of nanoparticles and increased solubility of drugs and drug targeting, resulting in increased cytotoxicity and cell death during BC treatment.
  • 1.1K
  • 22 Sep 2021
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