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Topic Review
Alveolar Epithelial Cells in Pulmonary Fibrosis
An important contributor to the development of idiopathic pulmonary fibrosis (IPF) is the alteration of the intracellular homeostasis of alveolar epithelial cells, which are mainly composed of alveolar type I epithelial cells (AT1), alveolar type II epithelial cells (AT2), as well as abnormal basaloid cells, resulting in aberrant epithelial repair, myofibroblast activation, and increased extracellular matrix deposition to form lung fibrosis
  • 629
  • 27 Feb 2023
Topic Review
Alternatively Spliced Isoforms in MAPK Signaling
The mitogen-activated protein kinase (MAPK) cascades are key signaling components  that transmit signals to many cellular processes. Each of the cascades operates by a sequential activation of protein kinases organized in three or more tiers that provide a seemingly linear signal transmission. However, the cellular effects regulated by each cascade may vary significantly. To achieve these diverse effects, the specificity of each cascade is extended by distinct regulators.  Here we describe the importance of having distinct components in each tier of the cascades, particularly alternatively spliced isoforms of the MAPK components. This mode of regulation extends the cascade’s specificity and allows accurate, fine-tuned signaling outcomes that lead to proper cell fates. 
  • 629
  • 28 Jan 2022
Topic Review
Histopathology of Interstitial Lung Disease
Interstitial lung diseases (ILD) are relatively rare and sometimes become life threatening. In particular, rapidly progressive ILD, which frequently presents as acute lung injury (ALI) on lung histopathology, shows poor prognosis if proper and immediate treatments are not initiated. These devastating conditions include acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), clinically amyopathic dermatomyositis (CADM), epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced lung injury, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection named coronavirus disease 2019 (COVID-19).
  • 627
  • 06 Dec 2022
Topic Review
Asbestos and Intrahepatic Cholangiocarcinoma
The link between asbestos exposure and the onset of thoracic malignancies is well established. However epidemiological studies have provided evidences that asbestos may be also involved in the development of gastrointestinal tumors, including intrahepatic cholangiocarcinoma (ICC). In line with this observation, asbestos fibers have been detected in the liver of patients with ICC. Although the exact mechanism still remains unknown, the presence of asbestos fibers in the liver could be explained in the light of their translocation pathway following ingestion/inhalation. In the liver, thin and long asbestos fibers could remain trapped in the smaller bile ducts, particularly in the stem cell niche of the canals of Hering, and exerting their carcinogenic effect for a long time, thus inducing hepatic stem/progenitor cells (HpSCs) malignant transformation. In this scenario, chronic liver damage induced by asbestos fibers over the years could be seen as a classic model of stem cell-derived carcinogenesis, where HpSC malignant transformation represents the first step of this process. This phenomenon could explain the recent epidemiological findings, where asbestos exposure seems mainly involved in ICC, rather than extrahepatic cholangiocarcinoma, development.
  • 627
  • 04 Jun 2021
Topic Review
L-Lactate
l-Lactate plays a role as a metabolic and signaling molecule, accordingly, Vaccari-Cardoso and co-workers developed a viral vector to express a modified version of lactate oxidase (LOx) originating from the bacteria Aerococcus viridans. Their results in vitro show that LOx expression in astrocytes reduced their intracellular lactate levels and its release to the extracellular space.
  • 624
  • 07 Oct 2021
Topic Review
TRIM
The tripartite motif (TRIM) gene family is a large group of E3 ubiquitin ligase proteins that can also have proteasome-independent functions. TRIM/RBCC are a large family of proteins that include more than 80 proteins, most of which act as E3 ligases and catalyze the direct transfer of Ubiquitin, SUMO and ISG15 on specific protein substrates. They are involved in oncogenesis processes and in cellular immunity.
  • 624
  • 19 May 2022
Topic Review
Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation
KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through the regulation of several downstream effectors. In cancer cells, KRAS mutations confer the constitutive activation of this oncogene, stimulating cell proliferation, inducing autophagy, suppressing apoptosis, altering cell metabolism, changing cell motility and invasion and modulating the tumor microenvironment.
  • 623
  • 21 Jul 2022
Topic Review
B Cells in Neuroinflammation
In recent years, the role of B cells in neurological disorders has substantially expanded our perspectives on mechanisms of neuroinflammation. The success of B cell-depleting therapies in patients with CNS diseases such as neuromyelitis optica and multiple sclerosis has highlighted the importance of neuroimmune crosstalk in inflammatory processes. While B cells are essential for the adaptive immune system and antibody production, they are also major contributors of pro- and anti-inflammatory cytokine responses in a number of inflammatory diseases. B cells can contribute to neurological diseases through peripheral immune mechanisms, including production of cytokines and antibodies, or through CNS mechanisms following compartmentalization. Emerging evidence suggests that aberrant pro- or anti-inflammatory B cell populations contribute to neurological processes, including glial activation, which has been implicated in the pathogenesis of several neurodegenerative diseases.
  • 623
  • 30 Jun 2021
Topic Review
PTEN Dual Lipid- and Protein-Phosphatase Function in Tumor
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a multifunctional tumor suppressor with protein- and lipid-phosphatase activities. The inactivation of PTEN is commonly found in all human cancers and is correlated with tumor progression. PTEN-lipid-phosphatase activity has been well documented to dephosphorylate phosphatidylinositol-3, 4, 5-phosphate (PIP3), which hinders cell growth and survival by dampening the PI3K and AKT signaling activity. PTEN-protein-phosphatase activity dephosphorylates the different proteins and acts in various cell functions. 
  • 623
  • 28 Sep 2022
Topic Review
PI3Ks, Targets of Cancer Therapeutics
Phosphatidylinositol 3-kinases (PI3Ks) are a family of enzymes responsible for phosphorylating the 3-hydroxyl group of the inositol ring of phosphatidylinositol.  PI3Ks are subdivided into three classes, class I, II, and III based on their structures, functions, and tissue distribution. PI3Ks are engaged in a range of cellular functions such as cell growth, proliferation differentiation, migration, survival, cell death, and intracellular trafficking. Many of these functions are related to the activity of class I PI3Ks family. Class I PI3Ks family generates phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5,)P3), which activates an assorted number of downstream molecules in the PI3K signaling pathway that are necessary for normal cellular growth and development. Elevated PI3K activity is considered as the hallmark of cancer, which is promoted by diverse oncogenes and growth factor receptors causing enhanced PI3K signaling. Several PI3K pathway inhibitors have been developed including pan-PI3K inhibitors and isoform-specific PI3K inhibitors. Some of the PI3K inhibitors have been approved for the treatment of various cancer types. Furthermore, to overcome drug resistance, improve efficacy, enhance synergy, and reduce toxicity, several different therapeutic approaches are being developed and some are in clinical trials. 
  • 622
  • 25 Nov 2020
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