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Topic Review
Erythrocytes for Targeted Drug Delivery
Erythrocytes (red blood cells, RBCs) are the largest population of blood cells in mammals. Their main function is oxygen transfer to cells and body tissues. The lifetime of erythrocytes in the bloodstream is 100–120 days, after which they are removed by the spleen. Due to the unique biophysical properties RBCs can be used as drug carriers in two different ways: by incorporating the drug into the cells or by binding it (using non-specific adsorption or a specific association, involving antibodies or various chemical cross-linking compounds) on the RBCs’ surface. Erythrocytes can act as carriers that prolong the drug’s action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes. 
  • 1.5K
  • 22 Apr 2022
Topic Review
Fibroblast Growth Factor 23 and Osteoporosis
Osteoporosis is a chronic debilitating disease caused by imbalanced bone remodeling processes that impair the structural integrity of bone. Over the last ten years, the association between fibroblast growth factor 23 (FGF23) and osteoporosis has been studied in both pre-clinical and clinical investigations. FGF23 is a bone-derived endocrine factor that regulates mineral homeostasis via the fibroblast growth factor receptors (FGFRs)/αKlotho complex. These receptors are expressed in kidney and the parathyroid gland. Preclinical studies have supported the link between the local actions of FGF23 on the bone remodeling processes. In addition, clinical evidence regarding the effects of FGF23 on bone mass and fragility fractures suggest potential diagnostic and prognostic applications of FGF23 in clinical contexts, particularly in elderly and patients with chronic kidney disease. However, inconsistent findings exist and there are areas of uncertainty requiring exploration.
  • 1.5K
  • 16 Mar 2022
Topic Review
Oromucosal Administration of Oxytocin: The Development of ‘Oxipops’
The neuropeptide oxytocin is synthesized by cells in the hypothalamic paraventricular and supraoptic nuclei and transported to the posterior pituitary for release into the blood, where it is most well-known for acting on smooth muscle to stimulate uterine contractions during labor and milk-ejection from the breast. The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research due, most notably, to its reported involvement in promoting social cognition and motivation, reducing anxiety, and relieving pain. It is also increasingly being considered as an important therapeutic intervention in a variety of disorders with social dysfunction as a symptom.  There is increasing evidence that many of its functional effects can be peripherally mediated via increasing its concentration in the blood. This has opened up an oromucosal administration route as an alternative, which is beneficial since the oral consumption of peptides is problematic due to their rapid breakdown in the acidic environment of the gastrointestinal system. 
  • 1.5K
  • 18 Mar 2024
Topic Review
Mechanisms of Skin Aging Processes
With the advancement of living standards in modern society and the emergence of an aging population, an increasing number of people are becoming interested in the topic of aging and anti-aging. An important feature of aging is skin aging, and women are particularly concerned about skin aging. In the field of cosmetics, the market share of anti-aging products is increasing year by year.
  • 1.5K
  • 01 Aug 2023
Topic Review
CT assessment of CLAD
Chronic lung allograft rejection remains one of the major causes of morbi-mortality after lung transplantation. The term Chronic Lung Allograft Dysfunction (CLAD) has been proposed to describe the different processes that lead to a significant and persistent deterioration in lung function without identifiable causes. The two main phenotypes of CLAD are Bronchiolitis Obliterans Syndrome (BOS) and Restrictive Allograft Syndrome (RAS), each of them characterized by particular functional and imaging features. These entities can be associated (mixed phenotype) or switch from one to the other. If CLAD remains a clinical diagnosis based on spirometry, computed tomography (CT) scan plays an important role in the diagnosis and follow-up of CLAD patients: •      To exclude identifiable causes of functional decline when CLAD is first suspected; •      To detect early abnormalities that can precede the diagnosis of CLAD (particularly RAS);  •      To differentiate between the obstructive and the restrictive phenotypes; •      To detect exacerbations and evolution from one phenotype to the other. Recognition of early signs of rejection is crucial, for better understanding of physiopathologic pathways and optimal management of patients. 
  • 1.5K
  • 19 May 2021
Topic Review
Proteins in Solid Pharmaceutical Forms
Therapeutic proteins as biopharmaceuticals have emerged as a very important class of drugs for the treatment of many diseases. However, they are less stable compared to conventional pharmaceuticals. Their long-term stability in solid forms, which is critical for product performance, depends heavily on the retention of the native protein structure during the lyophilization (freeze-drying) process and, thereafter, in the solid state. Indeed, the biological function of proteins is directly related to the tertiary and secondary structure. Besides physical stability and biological activity, conformational stability (three-dimensional structure) is another important aspect when dealing with protein pharmaceuticals. Moreover, denaturation as loss of higher order structure is often a precursor to aggregation or chemical instability. Careful study of the physical and chemical properties of proteins in the dried state is therefore critical during biopharmaceutical drug development to deliver a final drug product with built-in quality that is safe, high-quality, efficient, and affordable for patients. This review provides an overview of common analytical techniques suitable for characterizing pharmaceutical protein powders, providing structural, and conformational information, as well as insights into dynamics. Such information can be very useful in formulation development, where selecting the best formulation for the drug can be quite a challenge
  • 1.5K
  • 06 May 2021
Topic Review
Trace Amines
Trace amines are a chemical group of amines and their isomers, included in the biogenic amines’ family. They are natural compounds with low molecular weight, formed during the natural metabolism of animals, plants, and microorganisms from amino acids precursors.
  • 1.5K
  • 09 Dec 2022
Topic Review
Targeting TIGIT
TIGIT is a negative regulator of immune response known to bind to PVR ligands with greater affinity and outcompete the costimulatory receptors, CD226 and CD96, expressed on T cells, thereby inhibiting the activation, proliferation, and differentiation of T cells (). Further, TIGIT engagement ensures the survival of inhibited T cells by activating cell survival pathways. TIGIT activation on NK cells was shown to inhibit cytotoxic granule polarization and IFN-γ production and decrease NK cell cytotoxicity. In addition, TIGIT interaction on Tregs skews the cytokine balance, suppresses Th1 or Th17 phenotype, and induces Th2 phenotype.
  • 1.5K
  • 29 Mar 2022
Topic Review
Three-Dimensional Cell Culture Methods
Cells, the basic structures of all living organisms, reside in an extracellular matrix consisting of a complex three-dimensional architecture and interact with neighboring cells both mechanically and biochemically. Cell–cell and cell–extracellular matrix interactions form a three-dimensional network that maintains tissue specificity and homeostasis. Important biological processes in a cell cycle are regulated by principles organized by the microenvironment surrounding the cell. The conventional cell culture methods failed to mimic in vivo-like structural organization and are insufficient to examine features such as connectivity of cells, cellular morphology, viability, proliferation, differentiation, gene and protein expression, response to stimuli, and drug/vaccine metabolism. Three-dimensional cell culture studies are very important in terms of reducing the need for in vivo studies and creating an intermediate step.
  • 1.5K
  • 17 Jan 2023
Topic Review
Nrf2-Keap1-ARE Signaling and IRI
Ischemia/reperfusion (I/R) injury is associated with substantial clinical implications, including a wide range of organs such as the brain, kidneys, lungs, heart, and many others. I/R injury (IRI) occurs due to the tissue injury following the reestablishment of blood supply to ischemic tissues, leading to enhanced aseptic inflammation and stimulation of oxidative stress via reactive oxygen and nitrogen species (ROS/RNS). Since ROS causes membrane lipids’ peroxidation, triggers loss of membrane integrity, denaturation of proteins, DNA damage, and cell death, oxidative stress plays a critical part in I/R pathogenesis. Therefore, ROS regulation could be a promising therapeutic strategy for IRI. In this context, Nrf2 (NF-E2-related factor 2) is a transcription factor that regulates the expression of several factors involved in the cellular defense against oxidative stress and inflammation, including heme oxygenase-1 (HO-1). 
  • 1.5K
  • 01 Jun 2021
Topic Review
Histopathology of the Peripheral Neuroblastic Tumors
The word “neuroblastoma” is often used as an omnibus term for all peripheral neuroblastic tumors (pNTs), including neuroblastoma, ganglioneuroblastoma and ganglioneuroma. As well defined by Willis, neuroblastoma is an embryonal tumor of neural crest origin. We believe that all ganglioneuromas were once neuroblastomas in their early stage of tumor development. Tumors in this group are known to present with a wide range of clinical behaviors, such as spontaneous regression, tumor maturation and aggressive progression refractory to intensive treatment. Because of the difficulty in predicting clinical outcomes of the patients, neuroblastoma was described as an enigmatic disease for many years.
  • 1.4K
  • 29 Jan 2022
Topic Review
Peptides in Diagnostics
The specificity of a diagnostic assay depends upon the purity of the biomolecules used as a probe. To get specific and accurate information of a disease, the use of synthetic peptides in diagnostics have increased in the last few decades, because of their high purity profile and ability to get modified chemically. The discovered peptide probes are used either in imaging diagnostics or in non-imaging diagnostics. In non-imaging diagnostics, techniques such as Enzyme-Linked Immunosorbent Assay (ELISA), lateral flow devices (i.e., point-of-care testing), or microarray or LC-MS/MS are used for direct analysis of biofluids. Among all, peptide-based ELISA is considered to be the most preferred technology platform. Similarly, peptides can also be used as probes for imaging techniques, such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The role of radiolabeled peptides, such as somatostatin receptors, interleukin 2 receptor, prostate specific membrane antigen, αβ3 integrin receptor, gastrin-releasing peptide, chemokine receptor 4, and urokinase-type plasminogen receptor, are well established tools for targeted molecular imaging ortumor receptor imaging. Low molecular weight peptides allow a rapid clearance from the blood and result in favorable target-to-non-target ratios. It also displays a good tissue penetration and non-immunogenicity. The only drawback of using peptides is their potential low metabolic stability. 
  • 1.4K
  • 28 Sep 2021
Topic Review
Pyroptosis
Ischemia-reperfusion (I/R) injury, uncommon among patients suffering from myocardial infarction, stroke, or acute kidney injury, can result in cell death and organ dysfunction. Previous studies have shown that different types of cell death, including apoptosis, necrosis, and autophagy, can occur during I/R injury. Pyroptosis, which is characterized by cell membrane pore formation, pro-inflammatory cytokine release, and cell burst, and which differentiates itself from apoptosis and necroptosis, has been found to be closely related to I/R injury. 
  • 1.4K
  • 21 Nov 2022
Topic Review
The Role of BUB3 in Human Cancers
The BUB3 protein plays a key role in the activation of the spindle assembly checkpoint (SAC), a ubiquitous surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis and, consequently, prevents chromosome mis-segregation and aneuploidy. Besides its role in SAC signaling, BUB3 regulates chromosome attachment to the spindle microtubules. It is also involved in telomere replication and maintenance. Deficiency of the BUB3 gene has been closely linked to premature aging. Upregulation of the BUB3 gene has been found in a variety of human cancers and is associated with poor prognoses.
  • 1.4K
  • 25 May 2022
Topic Review
Clinical Significance of Taurine and Creatine Transporters
Cancer cells are characterized by uncontrolled growth, proliferation, and impaired apoptosis. Tumour progression could be related to poor prognosis and due to this fact, researchers have been working on novel therapeutic strategies and antineoplastic agents. It is known that altered expression and function of solute carrier proteins from the solute carrier 6 (SLC6) family (taurine (SLC6A6) and creatine (SLC6A8)) could be associated with severe diseases, including cancers. These proteins were noticed to play important physiological roles through transferring nutrient amino acids, osmolytes, neurotransmitters, and ions, and many of them are necessary for survival of the cells.
  • 1.4K
  • 22 Feb 2023
Topic Review
Experimental Animal Skin Flap Models
Skin flaps are necessary in plastic and reconstructive surgery for the removal of skin cancer, wounds, and ulcers. A skin flap is a portion of skin with its own blood supply that is partially separated from its original position and moved from one place to another. The use of skin flaps is often accompanied by cell necrosis or apoptosis due to ischemia–reperfusion (I/R) injury.
  • 1.4K
  • 20 May 2022
Topic Review
The Relaxin-3 Receptor in Aging-Related Disease
During the aging process human's body becomes less well equipped to deal with cellular stress, resulting in an increase in unrepaired damage. This causes varying degrees of impaired functionality and an increased risk of mortality. One of the most effective anti-aging strategies involves interventions that combine simultaneous glucometabolic support with augmented DNA damage protection/repair. Thus, it seems prudent to develop therapeutic strategies that target this combinatorial approach. Studies have shown that the ADP-ribosylation factor (ARF) GTPase activating protein GIT2 (GIT2) acts as a keystone protein in the aging process. GIT2 can control both DNA repair and glucose metabolism. Through in vivo co-regulation analyses it was found that GIT2 forms a close co-expression based relationship with the relaxin-3 receptor (RXFP3). Cellular RXFP3 expression is directly affected by DNA damage and oxidative stress. Overexpression or stimulation of this receptor, by its endogenous ligand relaxin 3 (RLN3), can regulate the DNA damage response and repair processes. Interestingly, RLN3 is an insulin-like peptide and has been shown to control multiple disease processes linked to aging mechanisms, e.g., anxiety, depression, memory dysfunction, appetite, and anti-apoptotic mechanisms.
  • 1.4K
  • 27 Sep 2022
Topic Review
Hydrogels with Antibacterial Agents for Bone Repair
Hydrogels are water-swollen hydrophilic materials that maintain a distinct three-dimensional structure, helping load various antibacterial drugs and biomolecules. Hybrid hydrogels may potentially possess antibacterial ability and osteogenic activity.
  • 1.4K
  • 27 May 2022
Topic Review
Biomarker-Driven Drug Development
Biomarker-driven drug development in age of personalized medicines. A biomarker life cycle is broken down into 3 stages - discovery, translation, and qualification. Researchers review current development strategies and technologies applied at each of these stages, with emphasis on the use of real-world data as an important source of supporting evidence.
  • 1.4K
  • 28 Apr 2022
Topic Review
Insulitis in Human Type 1 Diabetic Pancreas
Type 1 diabetes (T1D) is an autoimmune disease with immune cells’ islet infiltration (called “insulitis”), which leads to beta cell loss. Despite being the critical element of T1D occurrence and pathogenesis, insulitis is often present in a limited percentage of islets, also at diagnosis. Therefore, it is needed to define reproducible methods to detect insulitis and beta-cell decline, to allow accurate and early diagnosis and to monitor therapy. This goal is still far due to the morphological aspect of islet microvasculature, which is rather dense and rich, and is considerably rearranged during insulitis. More studies on microvasculature are required to understand if contrast-enhanced ultrasound sonography measurements of pancreatic blood-flow dynamics may provide a clinically deployable predictive marker to predict disease progression and therapeutic reversal in pre-symptomatic T1D patients. It is needed to clarify the relation between insulitis and the dynamics of β cell loss and with coexisting mechanisms of dysfunction, according to clinical stage, as well as the micro vessels’ dynamics and microvasculature reorganization. The ideal cell-based therapy of T1D should start from an early diagnosis allowing a sufficient isolation of specific Procr+ progenitors, followed by the generation and expansion of islet organoids, which could be transplanted coupled to an immune-regulatory therapy which will permit the maintenance of pancreatic islets and an effective and long-lasting insulitis reversal.
  • 1.4K
  • 14 Dec 2022
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