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Topic Review
IGF-IR Stimulating Activity Analyses
Insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) play a crucial factor in the growth, differentiation and survival of cells in health and disease. IGF-I and IGF-II primarily activate the IGF-I receptor (IGF-IR), which is present on the cell surface. Activation of the IGF-IR stimulates multiple pathways which finally results in multiple biological effects in a variety of tissues and cells. In addition, activation of the IGF-IR has been found to be essential for the growth of cancers. The conventional view in the past was that the IGF-IR was exclusively a tyrosine kinase receptor and that phosphorylation of tyrosine residues, after binding of IGF-I to the IGF-IR, started a cascade of post-receptor events. Research has shown that this view was too simplistic. It has been found that the IGF-IR also has kinase-independent functions and may even emit signals in the unoccupied state through some yet-to-be-defined non-canonical pathways. The IGF-IR may further form hybrids with the insulin receptors but also with receptor tyrosine kinases (RTKs) outside the insulin-IGF system. In addition, the IGF-IR has extensive cross-talk with many other receptor tyrosine kinases and their downstream effectors. Moreover, there is now emerging evidence that the IGF-IR utilizes parts of the G-protein coupled receptor (GPCR) pathways: the IGF-IR can be considered as a functional RTK/GPCR hybrid, which integrates the kinase signaling with some IGF-IR mediated canonical GPCR characteristics. Like the classical GPCRs the IGF-IR can also show homologous and heterologous desensitization.
  • 197
  • 07 Oct 2023
Topic Review
IL-33/IL-31 Axis in Autoimmune Disorders
Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet’s disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to immunoglobulin (Ig)E production, thus including key cytokines such as interleukin (IL)-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine—it regulates cell proliferation and is involved in tissue remodeling. IL-33, acting through its receptor suppression of tumorigenity (ST2L), is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions.
  • 256
  • 01 Aug 2023
Topic Review
Immunohistochemical Profile of Parathyroid Tumours
Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022).
  • 316
  • 28 Jul 2022
Topic Review
Immunotherapeutics in Gastric Cancer
Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored.
  • 413
  • 14 Apr 2021
Topic Review
Implications of Pituitary Tumorigenesis for Management
Pituitary neuroendocrine tumors (PitNETs), the third most common intracranial tumor, are mostly benign. However, some of them may display a more aggressive behavior, invading into the surrounding structures. While they may rarely metastasize, they may resist different treatment modalities. Several major advances in molecular biology led to the discovery of the possible mechanisms involved in pituitary tumorigenesis with a possible therapeutic implication. The mutations in the different proteins involved in the Gsa/protein kinase A/c AMP signaling pathway are well-known and are responsible for many PitNETS, such as somatotropinomas and, in the context of syndromes, as the McCune–Albright syndrome, Carney complex, familiar isolated pituitary adenoma (FIPA), and X-linked acrogigantism (XLAG). The other pathways involved are the MAPK/ERK, PI3K/Akt, Wnt, and the most studied HIPPO pathways. Moreover, the mutations in several other tumor suppressor genes, such as menin and CDKN1B, are responsible for the MEN1 and MEN4 syndromes and succinate dehydrogenase (SDHx) in the context of the 3PAs syndrome. 
  • 247
  • 26 May 2023
Topic Review
Inflammation and Hemorrhage/Coagulation in Primary Blast Lung Injury
Primary blast lung injury (PBLI), caused by exposure to high-intensity pressure waves from explosions in war, terrorist attacks, industrial production, and life explosions, is associated with pulmonary parenchymal tissue injury and severe ventilation insufficiency. PBLI patients, characterized by diffused intra-alveolar destruction, including hemorrhage and inflammation, might deteriorate into acute respiratory distress syndrome (ARDS) with high mortality. 
  • 381
  • 17 Feb 2023
Topic Review
Inflammation in Obesity
Obesity, as a part of metabolic syndrome, represents the leading factor for disability, and is correlated with higher inflammation status, morbidity, and mortality. Biomarkers of high-level chronic inflammation are recognized as important predictors of pro-inflammatory disease. Besides the well-known pro-inflammatory cytokines, such as WBCs (white blood cells), IL-1 (interleukin-1), IL-6 (interleukin-6), TNF-alpha (tumor necrosis factor-alpha), and hsCRP (high-sensitivity C-reactive protein), as well as anti-inflammatory markers, such as adiponectin and systemic inflammation, can be determined by a variety of blood tests as a largely available and inexpensive inflammatory biomarker tool.
  • 246
  • 13 Jun 2023
Topic Review
Injectable Hydrogels for Skin Wound
Functionalized biomaterials which are able to be implanted regardless of the wound deformity  and potentially embark the skin wound management by the ability to be bioinert, self-degradable and non invasive. These 3D network hold a unique characteristics which are able to mimic the skin extracellular matrix (ECM) and has been successfully proven to promote wound healing and skin regeneration.
  • 692
  • 31 May 2021
Topic Review
Instability of Peptide and Possible Causes of Degradation
Peptides are different from proteins. Although both are composed of amino acids, peptides are smaller molecules comprised of two or more amino acids linked by peptide bonds, while proteins are long chains of amino acids that may have a much larger number of amino acids. Peptide stability in aqueous solutions is critical when developing parenteral formulations, as the potency of a peptide is often compromised due to chemical or physical degradation pathways.
  • 1.5K
  • 29 Mar 2023
Topic Review
Insulin and Transcriptional Regulation of Lipid Metabolism
There is a wide variety of kinds of lipids, and complex structures which determine the diversity and complexity of their functions. With the basic characteristic of water insolubility, lipid molecules are independent of the genetic information composed by genes to proteins, which determine the particularity of lipids in the human body, with water as the basic environment and genes to proteins as the genetic system. After the well-studied PI3K-AKT pathway, insulin affects fat synthesis by controlling the activity and production of various transcription factors.
  • 261
  • 31 Oct 2022
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