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Topic Review
Obesity and Lipids
Recently, lipidomics has become an important branch of medical/clinical sciences similar to proteomics and genomics. Due to the much higher lipid accumulation in obese patients and many alterations in the compositions of various groups of lipids, the methods used for sample preparations for lipidomic studies of samples from obese subjects sometimes have to be modified. Appropriate sample preparation methods allow for the identification of a wide range of analytes by advanced analytical methods, including mass spectrometry. This is especially the case in studies with obese subjects, as the amounts of some lipids are much higher, others are present in trace amounts, and obese subjects have some specific alterations of the lipid profile. 
  • 827
  • 01 Dec 2020
Topic Review
Peretinoin
Peretinoin, an retinoid acid (RA), a metabolite of vitamin A and its related analogues (termed retinoids) has been suggested as a promising chemotherapeutic agent in cancer treatment. The synthetic oral retinoid peretinoin is the only agent for the secondary chemoprevention of HCC after curative therapy that is currently well applied into clinical development.
  • 827
  • 12 Oct 2021
Topic Review
TKS4 and TKS5 Scaffold Proteins
Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development. Furthermore, TKS4 has also been implicated in the regulation of homeostasis of mature adipose and bone tissue.
  • 826
  • 19 Jan 2021
Topic Review
Topical Insulin Delivery
Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. 
  • 825
  • 13 Sep 2021
Topic Review
The HSP40/DnaJ Proteins Existing in Leishmania
Abrupt environmental changes are faced by Leishmania parasites during transmission from a poikilothermic insect vector to a warm-blooded host. Adaptation to harsh environmental conditions, such as nutrient deprivation, hypoxia, oxidative stress and heat shock needs to be accomplished by rapid reconfiguration of gene expression and remodeling of protein interaction networks. Chaperones play a central role in the maintenance of cellular homeostasis, and they are responsible for crucial tasks such as correct folding of nascent proteins, protein translocation across different subcellular compartments, avoiding protein aggregates and elimination of damaged proteins. Nearly one percent of the gene content in the Leishmania genome corresponds to members of the HSP40 family, a group of proteins that assist HSP70s in a variety of cellular functions. 
  • 825
  • 12 May 2022
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.
  • 823
  • 30 Oct 2020
Topic Review
Antibody-Based Immunotherapy for Metastatic Melanoma
Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g., chemotherapy), BRAF inhibitor treatment has shown improved therapeutic outcomes. Photodynamic therapy (PDT) relies on a light-activated compound to produce death-inducing amounts of reactive oxygen species (ROS). Their capacity to selectively accumulate in tumor cells has been confirmed in melanoma treatment with some encouraging results. However, this treatment approach has not reached clinical fruition for melanoma due to major limitations associated with the development of resistance and subsequent side effects. These adverse effects might be bypassed by immunotherapy in the form of antibody–drug conjugates (ADCs) relying on the ability of monoclonal antibodies (mAbs) to target specific tumor-associated antigens (TAAs) and to be used as carriers to specifically deliver cytotoxic warheads into corresponding tumor cells. Of late, the continued refinement of ADC therapeutic efficacy has given rise to photoimmunotherapy (PIT) (a light-sensitive compound conjugated to mAbs), which by virtue of requiring light activation only exerts its toxic effect on light-irradiated cells.
  • 823
  • 26 Oct 2020
Topic Review
Lysine63Ubiquitination and Fibrosis in Diabetes
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. We previously showed that tubulo-interstitial accumulation of lysine 63 (K63)-ubiquitinated (Ub) proteins drives the progression of fibrosis in DN and that the extent of renal K63-Ub can be easily monitored through the assessment of urinary miR-27b-3p. In the present manuscript we explored the renoprotective effect of a specific K63-Ub inhibitor (NSC697923), alone and in combination with the ACE inhibitor molecule Ramipril. In vitro, in tubular epithelial cells, we found that NSC697923, aside from suppressing tubular accumulation of K63-Ub proteins was also capable to inhibit hyperglycemia-induced epithelial to mesenchymal transition (EMT); specifically, treatment with NSC697923 reduced the expression of EMT markers such as α-SMA, Collagen I, Vimentin, FSP-1 and Collagen III along with tubulointerstitial and glomerular fibrosis both in vitro and in vivo. Diabetic DBA/2J mice treated with NSC697923 also displayed recovery of urinary miR-27b-3p and restored expression of p16INK4A, indicating a protective effect of this compund on cellular senescence in tubular cells. Moreover, we found that the combination of NSC697923 and Ramipril was effective to reduce uACR in diabetic DBA/2J mice. In conclusion, we suggest that selective inhibition of K63-Ub, when combined with the conventional treatment with ACE inhibitors, might represent a novel treatment strategy to prevent the progression of fibrosis and proteinuria in DN. Finally we suggest the dosage of urinary miR-27b-3p levels to monitor treatment efficacy.
  • 823
  • 23 Jun 2021
Topic Review
Traveling Across Life Sciences with Acetophenone
Each metabolite, regardless of its molecular simplicity or complexity, has a mission or function in the organism biosynthesizing it.  The biological, allelochemical, and chemical properties of acetophenone, as a metabolite involved in multiple interactions with various (mi-cro)organisms.
  • 823
  • 28 Jan 2023
Topic Review
The Neuroprotective Potentiality of Flavonoids on Alzheimer’s Disease
Flavonoids are ubiquitous compounds of plants, produced by plants for growth and defense against all kinds of stress, including cold tolerance. More than 6000 different flavonoids have been identified, the primary sources of which are apples, red fruits, onions, citrus fruits, nuts, and beverages such as tea, coffee, beer, and red wine. These compounds, derived from phenol, are particularly interesting for their ability to cross the blood–brain barrier and for their multi-target activity. Several studies have described flavonoids to exhibit relevant biologic activities involving the neuronal antioxidants, as well as anti-amyloidogenic properties, acting as metal chelators, showing anti-inflammatory properties, and ameliorating cognition and neuroprotection.
  • 821
  • 12 Dec 2022
Topic Review
Carbon-Based Nanomolecules Interacting with Proteins
Scientists are designing new ways to combine proteins and carbon-based nanomomecules. We review strategies of selecting proteins able to interact with proteins and typical van der Waals interactions. Proteins and carbon based nanomomecules can form ordered clusters of hybrid materials and will guide new projects for bioimaging tools and tuning of intrinsically disordered proteins.
  • 820
  • 27 Oct 2020
Topic Review
IL-6 Signaling in colorectal cancer onset and progression
IL-6 is a pleiotropic cytokine showing both pro- and anti-inflammatory roles.
  • 820
  • 10 Dec 2021
Topic Review
KRAS and the Inflammatory Tumor Microenvironment Modulation
The TME is a dynamic network composed, not only by tumor cells, but also by several non-tumor cell types, including stromal cells as immune cells (macrophages, neutrophils, dendritic and natural killer cells, myeloid-derived suppressor cells (MDSCs), B and T cells), fibroblasts, adipocytes, endothelial cells, neurons, osteoblasts, osteoclasts, and the extracellular matrix (ECM). This non-cellular component, together with the tumor and the non-tumor cells, establish a dynamic, challenging microenvironment that can be modulated, but especially modulates cancer cell activities, dictating the success of tumor progression. Inflammation has been gradually recognized as a key initiator and contributor for tumorigenesis by orchestrating the immune surveillance and the immune escape, but also by affecting treatment response. Interestingly, the concept of tumor-promoting inflammation has been tightly associated with KRAS mutations. In fact, in colorectal cancers, the majority of the cases with a high prevalence of KRAS mutations correlate with chronic inflammatory diseases. KRAS and its downstream interactors are described as capable of shaping the immune microenvironment through the induction of the nuclear factor kappa light chain enhancer of activated B cells (NF)-kB signaling, which in turn promotes the transcription of several cytokines and chemokines, including interleukin (IL)-1α/β, IL-6, tumor necrosis factor α (TNF-α), Cys-X-Cys Chemokine (CXCL)-1, 2, 5, and 8, monocyte chemoattractant protein 1 (MCP-1 or CCL2), inducible nitric oxide synthase (iNOS), intracellular adhesion molecule 1 (ICAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM1). Independently of NF-kB, KRAS-downstream partners, such as RAF/MAPK and PI3K, may also induce IL-10, transforming growth factor β (TGF-β) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression. Several studies already reported that KRAS mutations could drive the secretion of anti-inflammatory cytokines, such as IL-10 and TGF-β, with the ability to sustain an immunosuppressive TME, whereas other studies verified that KRAS mutations could interfere with the secretion of pro-inflammatory cytokines, such as ICAM-1, TNF-α, IL-1β, IL-6, and IL-18. Thus, KRAS seems to act as a modulator of both an anti-inflammatory and a pro-inflammatory TME.
  • 820
  • 22 Feb 2022
Topic Review
Apoptosis-Associated Protein Domains
There are proteins or families of proteins that regulate the caspase activation pathways, namely, the extrinsic or intrinsic pathways, and they are identified depending on their amino acid sequence or homologue. The interactions facilitated by these protein families are driven through protein domains that are linked with the regulation of apoptosis, such as death domains (DDs), caspase recruitment domains (CARDs), death effector domains (DEDs), BCL-2 family proteins and of IAP-family proteins.
  • 820
  • 27 Apr 2022
Topic Review
Pulmonary Stem Cell Senescence and Differentiation Disorders
Pulmonary senescence is accelerated by unresolved DNA damage response, underpinning susceptibility to pulmonary fibrosis. Recently it was reported that the SARS-Cov-2 viral infection induces acute pulmonary epithelial senescence followed by fibrosis. Notably, the TGF-β signalling pathway mediates alveolar epithelial stem cell senescence by mechanisms involving suppression of the telomerase reverse transcriptase gene in pulmonary fibrosis. Alternatively, telomere uncapping caused by stress-induced telomeric shelterin protein TPP1 degradation mediates DNA damage response, pulmonary senescence and fibrosis. However, targeted intervention of cellular senescence disrupts pulmonary remodelling and fibrosis by clearing senescent cells using senolytics or preventing senescence using telomere dysfunction inhibitor (TELODIN). Studies indicate that the development of senescence-associated differentiation disorders is reprogrammable and reversible by inhibiting stem cell replicative senescence in pulmonary fibrosis, providing a framework for targeted intervention of the molecular mechanisms of alveolar stem cell senescence and pulmonary fibrosis.
  • 820
  • 18 Mar 2022
Topic Review
Usefulness of Microbiome for Forensic Geolocation
Forensic microbiomics is a promising tool for crime investigation. Geolocation connects an individual to a certain place or location by microbiota.
  • 819
  • 16 Dec 2021
Topic Review
Oxygen-Based Molecules
Oxygen-based compounds are an instrumental part of the group of small, relatively reactive molecules which control cellular activities. Traditionally such molecules have been referred to as the reactive oxygen species (ROS) and include hydrogen peroxide (H2O2), superoxide (O2∙−), and hydroxyl radicals (∙OH). However, several other reactive signaling molecules also contain oxygen, although referred to as reactive nitrogen species (RNS). These include nitric oxide (NO) and peroxynitrite (ONOO−), and therefore could be grouped together with the ROS as oxygen-based compounds. 
  • 818
  • 04 Aug 2021
Topic Review
EVs as Potential-Biomarkers in MS
       Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and its pathophysiology is characterized by a progressive blood-brain barrier dysfunction accompanied by infiltration in the central nervous system of peripheral pathogenic immune cells and inflammatory mediators leading to demyelination, axonal damage, and dysfunction and/or loss of synapses. Accumulating evidence highlights blood and cerebrospinal fluid (CSF) derived extracellular vesicles (EVs) as potential biomarkers of MS disease stages and of response to treatment. In particular, EVs released from blood–brain barrier (BBB) endothelial cells, platelets, leukocytes, myeloid cells, astrocytes, and oligodendrocytes seem to be involved in the pathogenesis of MS and of its rodent model experimental autoimmune encephalomyelitis. Further research is necessary to validate these observations and the screening of specific EVs subsets based on their cargo and membrane compositions associated to specific MS pathophysiological mechanisms might help guiding MS diagnosis, prognosis, and response to therapy. 
  • 817
  • 28 Sep 2021
Topic Review
Molecular Mechanisms of Muscle Fatigue
Muscle fatigue (MF) declines the capacity of muscles to complete a task over time at a constant load. MF is usually short-lasting, reversible, and is experienced as a feeling of tiredness or lack of energy. The leading causes of short-lasting fatigue are related to overtraining, undertraining/deconditioning, or physical injury. Conversely, MF can be persistent and more serious when associated with pathological states or following chronic exposure to certain medication or toxic composites. In conjunction with chronic fatigue, the muscle feels floppy, and the force generated by muscles is always low, causing the individual to feel frail constantly. The leading cause underpinning the development of chronic fatigue is related to muscle wasting mediated by aging, immobilization, insulin resistance (through high-fat dietary intake or pharmacologically mediated Peroxisome Proliferator-Activated Receptor (PPAR) agonism), diseases associated with systemic inflammation (arthritis, sepsis, infections, trauma, cardiovascular and respiratory disorders (heart failure, chronic obstructive pulmonary disease (COPD))), chronic kidney failure, muscle dystrophies, muscle myopathies, multiple sclerosis, and, more recently, coronavirus disease 2019 (COVID-19). The primary outcome of displaying chronic muscle fatigue is a poor quality of life. 
  • 817
  • 29 Nov 2021
Topic Review
Sodium-Glucose Co-Transporter 2 Inhibitors
Sodium-glucose co-transporter 2 (SGLT2) inhibitors facilitate urine glucose excretion by reducing glucose reabsorption, leading to ameliorate glycemic control. While the main characteristics of type 2 diabetes mellitus are insufficient insulin secretion and insulin resistance, SGLT2 inhibitors have some favorable effects on pancreatic β-cell function and insulin sensitivity. SGLT2 inhibitors ameliorate fatty liver and reduce visceral fat mass.
  • 817
  • 11 May 2021
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