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Topic Review
Flavones in Hypertensive Disease
Hypertension is the leading remediable risk factor for cardiovascular morbidity and mortality in the United States. Excess dietary salt consumption, which is a catalyst of hypertension, initiates an inflammatory cascade via activation of antigen-presenting cells (APCs). This pro-inflammatory response is driven primarily by sodium ions (Na+) transporting into APCs by the epithelial sodium channel (ENaC) and subsequent NADPH oxidase activation, leading to high levels of oxidative stress. Flavonoids, a natural phenolic compound, have these therapeutic benefits and can potentially serve as anti-hypertensives. Flavones are a type of flavonoid that have increased anti-inflammatory effects that may allow them to act as therapeutic agents for hypertension, including diosmetin, which is able to induce significant arterial vasodilation in several different animal models.
  • 328
  • 02 Nov 2023
Topic Review
Dental Follicle Cells Driving Osteogenic Differentiation
When research on osteogenic differentiation in dental follicle cells (DFCs) began, projects focused on bone morphogenetic protein (BMP) signaling. The BMP pathway induces the transcription factor DLX3, whichh in turn induces the BMP signaling pathway via a positive feedback mechanism. However, this BMP2/DLX3 signaling pathway only seems to support the early phase of osteogenic differentiation, since simultaneous induction of BMP2 or DLX3 does not further promote differentiation. Data showed that inhibition of classical protein kinase C (PKCs) supports the mineralization of DFCs and that osteogenic differentiation is sensitive to changes in signaling pathways, such as protein kinase B (PKB), also known as AKT. Small changes in the lipidome seem to confirm the participation of AKT and PKC in osteogenic differentiation. 
  • 255
  • 01 Nov 2023
Topic Review
Astrocytes as Glutamate Producers and Targets in ALS
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons (MNs) in the motor cortex, brainstem, and spinal cord. ALS involves different cell types, such as neurons, astrocytes, microglia, and oligodendrocytes. Since all these cells express the same mutated genes in patients, ALS can arise from a combination of damaged MNs and their glial partners rather than only from the neuronal lineage. Many studies highlighted the solid non-neuronal signature in ALS and suggested astrocytes and microglia as critical players in disease progression rather than disease onset. Conversely, data support an alteration of oligodendrocyte function at the disease pre-symptomatic and early symptomatic stages.
  • 179
  • 01 Nov 2023
Topic Review
Ceramide Synthase 2 in Bladder Cancer
The human CERS2 gene encodes a ceramide synthase enzyme, known as CERS2 (ceramide synthase 2). This protein is also known as LASS2 (LAG1 longevity assurance homolog 2) and TMSG1 (tumor metastasis-suppressor gene 1). Bladder cancer (BC) is a significant cause of cancer-related deaths globally, ranking as the second-most-common reason for genitourinary cancer-related mortality. The treatment of non-muscle invasive bladder cancer includes transurethral resection followed by chemotherapy to reduce recurrence chances, while muscle-invasive bladder cancers are associated with high rates of progression and metastasis and are usually treated via radical cystectomy if the tumor is organ-confined.
  • 268
  • 31 Oct 2023
Topic Review
Molecular Anatomy of the Prostate
Understanding prostate carcinogenesis is crucial not only for identifying new treatment targets but also for developing effective strategies to manage the asymptomatic form of the disease. There is a lack of consensus about predicting the indolent form of the disease prostate cancer, leading to uncertainties regarding treatment initiation.
  • 207
  • 27 Oct 2023
Topic Review
Navigating the ERK1/2 MAPK Cascade
The RAS-ERK pathway is a fundamental signaling cascade crucial for many biological processes including proliferation, cell cycle control, growth, and survival; common across all cell types. Notably, ERK1/2 are implicated in specific processes in a context-dependent manner as in stem cells and pancreatic β-cells. Alterations in the different components of this cascade result in dysregulation of the effector kinases ERK1/2 which communicate with hundreds of substrates. Aberrant activation of the pathway contributes to a range of disorders, including cancer.
  • 712
  • 25 Oct 2023
Topic Review
Protein-Bound Uremic Toxins in Senescence and Kidney Fibrosis
Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Studies gave some clues that PBUTs may also promote senescence in kidney tubular cells. 
  • 147
  • 25 Oct 2023
Topic Review
Emerging Roles of Ubiquitination in Biomolecular Condensates
Biomolecular condensates are dynamic non-membrane-bound macromolecular high-order assemblies that participate in a growing list of cellular processes, such as transcription, the cell cycle, etc. Disturbed dynamics of biomolecular condensates are associated with many diseases, including cancer and neurodegeneration. Extensive efforts have been devoted to uncovering the molecular and biochemical grammar governing the dynamics of biomolecular condensates and establishing the critical roles of protein posttranslational modifications (PTMs) in this process.
  • 177
  • 23 Oct 2023
Topic Review
Iron, Ferroptosis, and Head and Neck Cancer
Ferroptosis is an iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation. It plays a critical role not only in promoting drug resistance in tumors, but also in shaping therapeutic approaches for various malignancies. 
  • 245
  • 20 Oct 2023
Topic Review
The Ca2+ Sensor STIM in Human Diseases
The STIM family of proteins plays a crucial role in a plethora of cellular functions through the regulation of store-operated Ca2+ entry (SOCE) and, thus, intracellular calcium homeostasis. The two members of the mammalian STIM family, STIM1 and STIM2, are transmembrane proteins that act as Ca2+ sensors in the endoplasmic reticulum (ER) and, upon Ca2+ store discharge, interact with and activate the Orai/CRACs in the plasma membrane. Dysregulation of Ca2+ signaling leads to the pathogenesis of a variety of human diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and immune disorders. 
  • 261
  • 19 Oct 2023
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