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Topic Review
NF-κB-Dependent and -Independent IκBα Functions
IκBα is considered to play an almost exclusive role as inhibitor of the NF-κB signaling pathway. However, previous results have demonstrated that SUMOylation imposes a distinct subcellular distribution, regulation, NF-κB-binding affinity and function to the IκBα protein. In this review we discuss the main alterations of IκBα found in cancer and whether they are (most likely) associated with NF-κB-dependent or NF-κB-independent (moonlighting) activities of the protein.
  • 1.5K
  • 19 Oct 2021
Topic Review
Epicardial Thoracoscopic Ablation
In this study we evaluated atrial fibrillation (AF) recurrence and Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) levels in patients treated by epicardial thoracoscopic ablation for persistent AF. This was a prospective, multicenter, observational study to recruit patients with persistent AF receiving an epicardial thoracoscopic pulmonary vein isolation. About 27 patients, responders (n = 15) did not present AF recurrence after epicardial ablation at one-year follow-up; these patients displayed a marked remodeling of the left atrium, with a significant reduction of inflammatory cytokines, B type natriuretic peptide (BNP), and increased levels of SERCA compared to baseline and to non responders (p < 0.05). Furthermore, mean AF duration (Heart rate (HR) 1.235 (1.037-1.471), p < 0.05), Left atrium volume (LAV) (HR 1.755 (1.126-2.738), p < 0.05), BNP (HR 1.945 (1.895-1.999), p < 0.05), and SERCA (HR 1.763 (1.167-2.663), p < 0.05) were predictive of AF recurrence. Therefore, our data indicate for the first time that baseline values of SERCA in patients with persistent AF might be predictive of failure to epicardial ablative approach. Intriguingly, epicardial ablation was associated with increased levels of SERCA in responders. Thus, SERCA might be an innovative therapeutic target to improve the response to epicardial ablative treatments.
  • 1.5K
  • 28 Oct 2020
Topic Review
Colorectal Cancer
Colorectal cancer (CRC) is the third leading cause of cancer death in the world. Treatment with 5-Fluorouracil (5-FU) is known to improve survival in CRC patients. Most anti-cancer therapies trigger apoptosis induction to eliminate malignant cells. However, treatment resistance is a major challenge in the development of effective therapies. The microRNAs (miRNAs) play important roles in CRC treatment resistance and CRC progression and apoptosis. This review discusses the role of miRNAs in contributing to the promotion or inhibition of apoptosis in CRC and the role of miRNAs in modulating treatment resistance in CRC cells.
  • 1.5K
  • 09 Apr 2021
Topic Review
Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) is a congenital neuromuscular disorder characterized by motor neuron loss, resulting in progressive weakness. SMA is notable in the health care community because it accounts for the most common cause of infant death resulting from a genetic defect. SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from SMN1 gene mutations or deletions. However, patients always harbor various copies of SMN2, an almost identical but functionally deficient copy of the gene. A genotype–phenotype correlation suggests that SMN2 is a potent disease modifier for SMA, which also represents the primary target for potential therapies. Increasing comprehension of SMA pathophysiology, including the characterization of SMN1 and SMN2 genes and SMN protein functions, has led to the development of multiple therapeutic approaches. Until the end of 2016, no cure was available for SMA, and management consisted of supportive measures. Two breakthrough SMN-targeted treatments, either using antisense oligonucleotides (ASOs) or virus-mediated gene therapy, have recently been approved. These two novel therapeutics have a common objective: to increase the production of SMN protein in MNs and thereby improve motor function and survival. However, neither therapy currently provides a complete cure. Treating patients with SMA brings new responsibilities and unique dilemmas. As SMA is such a devastating disease, it is reasonable to assume that a unique therapeutic solution may not be sufficient. Current approaches under clinical investigation differ in administration routes, frequency of dosing, intrathecal versus systemic delivery, and mechanisms of action. Besides, emerging clinical trials evaluating the efficacy of either SMN-dependent or SMN-independent approaches are ongoing.
  • 1.5K
  • 30 Oct 2020
Topic Review
Cripto-1 in Tumor Progression
Cripto-1 is an essential protein for human development that plays a key role in the early phase of gastrulation in the differentiation of an embryo as well as assists with wound healing processes. Importantly, Cripto-1 induces epithelial to mesenchymal transition to turn fixed epithelial cells into a more mobile mesenchymal phenotype through the downregulation of epithelial adhesion molecules such as E-cadherin, occludins, and claudins, and the upregulation of mesenchymal, mobile proteins, such as N-cadherin, Snail, and Slug. Consequently, Cripto-1’s role in inducing EMT to promote cell motility is beneficial in embryogenesis, but detrimental in the formation, progression and metastasis of malignant tumors. Indeed, Cripto-1 is found to be upregulated in most cancers, such as breast, lung, gastrointestinal, hepatic, renal, cervical, ovarian, prostate, and skin cancers. Through its role in EMT, Cripto-1 can remodel cancer cells to enable them to travel through the extracellular matrix as well as blood and lymphatic vessels to metastasize to different organs. Additionally, Cripto-1 promotes the survival of cancer stem cells, which can lead to relapse in cancer patients. 
  • 1.5K
  • 06 Sep 2021
Topic Review
Genetic Characterization of Endometriosis
The purpose of this study was to evaluate the recent literature on the genetic characterization of women affected by endometriosis and to evaluate the influence of polymorphisms of the wingless-type mammalian mouse tumour virus integration site family member 4 (WNT4), vezatin (VEZT), and follicle stimulating hormone beta polypeptide (FSHB) genes, already known to be involved in molecular mechanisms associated with the proliferation and development of endometriotic lesions.
  • 1.5K
  • 06 Nov 2020
Topic Review
Liquid Biopsy of Brain Tumors
Direct biopsies obtain tissue material from the primary tumor, either via neurosurgical removal of all or most parts of a tumor or via stereotactic tissue biopsy. In contrast, a liquid biopsy uses body fluids collected distant to the brain tumor, such as venous blood from the arm or cerebrospinal fluid (CSF) via lumbar or cisternal puncture.
  • 1.5K
  • 25 Dec 2025
Topic Review
Brassica Bioactives May Ameliorate Endometriosis
Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are affected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not efficient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates.
  • 1.5K
  • 22 Dec 2020
Topic Review
HGF/MET
Unlike in normal epithelium, dysregulated overactivation of various proteases have been reported in cancers. Degradation of pericancerous extracellular matrix leading to cancer cell invasion by matrix metalloproteases is well known evidence. On the other hand, several cell-surface proteases, including type II transmembrane serine proteases (TTSPs), also induce progression through activation of growth factors, protease activating receptors and other proteases. Hepatocyte growth factor (HGF) known as a multifunctional growth factor that upregulates cancer cell motility, invasiveness, proliferative, and anti-apoptotic activities through phosphorylation of MET (a specific receptor of HGF). HGF secreted as inactive zymogen (pro-HGF) from cancer associated stromal fibroblasts, and the proteolytic activation by several TTSPs including matriptase and hepsin is required. The activation is strictly regulated by HGF activator inhibitors (HAIs) in physiological condition. However, downregulation is frequently observed in cancers. Indeed, overactivation of MET by upregulation of matriptase and hepsin accompanied by the downregulation of HAIs in urological cancers (prostate cancer, renal cell carcinoma, and bladder cancer) are also reported, a phenomenon observed in cancer cells with malignant phenotype, and correlated with poor prognosis.
  • 1.5K
  • 29 Oct 2020
Topic Review
Fragile X-Associated Tremor/Ataxia Syndrome
Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder seen in older premutation (55–200 CGG repeats) carriers of FMR1. Three molecular mechanisms have been proposed: (1) the production of toxic FMRpolyG by repeat-associated non-AUG (RAN) translation, (2) RNAs and protein sequestration into intranuclear inclusions and (3) DNA damage caused by R-loop formation. Additionally, mitochondrial dysfunction, oxidative stress, and iron metabolism dysregulation also play a role in the development of the neuropathology of FXTAS. One of the neuropathological hallmarks of FXTAS is the presence of eosinophilic intranuclear inclusions in the CNS and peripheral nervous system. Other findings include cerebral atrophy, ventriculomegaly, and spongiosis of the cerebellar white matter. The mechanisms underlying the pathophysiology of FXTAS are currently being investigated for the development of targeted treatment. 
  • 1.5K
  • 10 Nov 2020
Topic Review
Molecular Hydrogen Neuroprotection in Post-Ischemic Brain Injury
Molecular hydrogen has gained the attention of both preclinical and clinical researchers. The death of pyramidal neurons in especially the CA1 area of the hippocampus, increased permeability of the blood-brain barrier, neuroinflammation, amyloid accumulation, tau protein dysfunction, brain atrophy, cognitive deficits and dementia are considered an integral part of the phenomena occurring during brain neurodegeneration after ischemia.
  • 1.5K
  • 01 Jul 2022
Topic Review
Methanethiol: A Scent Mark of Cancer
Dysregulation of sulfur metabolism may result in elevated levels of volatile sulfur compounds (VSCs) in body fluids, breath, and/or excretions of cancer patients. Besides hydrogen sulfide (H2S), methanethiol is the predominant cancer-associated VSC and has been proposed as a promising biomarker for non-invasive cancer diagnosis. Gut bacteria are the major exogenous source of exposure to this foul-smelling toxic gas, with methanethiol-producing strains such as Fusobacterium nucleatum highly abundant in the gut microbiome of colorectal carcinoma (CRC) patients. Physiologically, methanethiol becomes rapidly degraded through the methanethiol oxidase (MTO) activity of selenium-binding protein 1 (SELENBP1). However, SELENBP1, which is considered a tumor suppressor, is often downregulated in tumor tissues, and this has been epidemiologically linked to poor clinical outcomes. In addition to impaired removal, an increase in methanethiol levels may derive from non-enzymatic reactions, such as a Maillard reaction between glucose and methionine, two metabolites enriched in cancer cells. High methionine concentrations in cancer cells may also result in enzymatic methanethiol production in mitochondria. Moreover, enzymatic endogenous methanethiol production may occur through methyltransferase-like protein 7B (METTL7B), which is present at elevated levels in some cancers, including CRC and hepatocellular carcinoma (HCC). In conclusion, methanethiol contributes to the "scent of cancer" as part of the cancer-associated signature combination of volatile organic compounds (VOCs).
  • 1.5K
  • 12 Oct 2023
Topic Review
Dry Eye and Probiotics
Probiotics are defined as live microorganisms that present health benefits when administered in adequate amounts. Prebiotics refer to substrates that microorganisms use to bestow health benefits upon host. Evidence regarding their effects on the ocular surface, especially dry eye, are now just emerging. Both rodent and human studies regarding gut microbiota in Sjögren’s syndrome and environmental dry eye are explored, and we discussed the effects of prebiotics and probiotics on dry eye in this section. 
  • 1.5K
  • 06 Jul 2021
Topic Review
FAK Family Kinases
In various vascular diseases, extracellular matrix (ECM) and integrin expression are frequently altered, leading to FAK or Pyk2 activation. In addition to the major roles of FAK and Pyk2 in regulating adhesion dynamics via integrins, recent studies have shown a new role of nuclear FAK in gene regulation in various vascular cells. In particular, FAK primarily localizes within the nuclei of vascular smooth muscle cells (VSMCs) of healthy arteries. However, vessel injury increased FAK localization back to adhesions and elevated FAK activity, leading to VSMC hyperplasia. The study suggested that abnormal FAK or Pyk2 activation in vascular cells may cause pathological condition in vascular diseases. Here we will review several studies of FAK and Pyk2 associated with integrin signaling in vascular diseases including restenosis, atherosclerosis, heart failure, pulmonary arterial hypertension, aneurysm, and thrombosis. Despite the importance of FAK family kinases in vascular diseases, comprehensive reviews are scarce. Therefore, we summarized animal models involving FAK family kinases in vascular diseases
  • 1.5K
  • 27 Oct 2020
Topic Review
Polyphenols and Ischemic Stroke
Stroke is now the second leading cause of death worldwide, and is defined as an impairment in blood supply to the brain, and is linked to different cardiovascular dysfunctions. Two main types of stroke exist: ischemic stroke (due to clot-mediated blood vessel occlusion), which accounts for about 85% of all stroke cases, and hemorrhagic stroke (caused by blood vessel rupture), which accounts for 15% of total cases. Following the stroke, while the core region undergoes sudden death, the surrounding injured regions (called penumbra) may be able to recover their functions.
  • 1.4K
  • 23 Jun 2021
Topic Review
High-Density Lipoproteins as Homeostatic Nanoparticles
It is well known that blood lipoproteins (LPs) are multimolecular complexes of lipids and proteins that play a crucial role in lipid transport. High-density lipoproteins (HDL) are a class of blood plasma LPs that mediate reverse cholesterol transport (RCT)—cholesterol transport from the peripheral tissues to the liver. Due to this ability to promote cholesterol uptake from cell membranes, HDL possess antiatherogenic properties. This function was first observed at the end of the 1970s to the beginning of the 1980s, resulting in high interest in this class of LPs. It was shown that HDL are the prevalent class of LPs in several types of living organisms (from fishes to monkeys) with high resistance to atherosclerosis and cardiovascular disorders. Lately, understanding of the mechanisms of the antiatherogenic properties of HDL has significantly expanded. Besides the contribution to RCT, HDL have been shown to modulate inflammatory processes, blood clotting, and vasomotor responses. These particles also possess antioxidant properties and contribute to immune reactions and intercellular signaling.
  • 1.4K
  • 30 Nov 2020
Topic Review
Aortic Valve Calcification
Aortic valve stenosis (AS) is the most common valvular heart disease. The incidence of AS increases with age, however, a significant proportion of elderly people have no significant AS, indicating that both aging and nonaging pathways are involved in the pathomechanism of AS.
  • 1.4K
  • 14 Nov 2022
Topic Review
Benign Prostatic Hyperplasia (BPH)
Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate and can cause obstructive and irritating lower urinary tract symptoms (LUTS); this proliferative change affects smooth muscle and epithelial cells within the transition zone of the prostate.
  • 1.4K
  • 03 Mar 2021
Topic Review
Focal Adhesion Kinase Inhibitors
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kinase activity in the cytoplasm, mainly dependent on the integrin signaling, and a scaffolding activity into the nucleus by networking with different gene expression regulators. For this reason, FAK has to be considered a target with high therapeutic values. Indeed, evidence suggests that FAK targeting could be effective, either alone or in combination, with other already available treatments.
  • 1.4K
  • 25 Feb 2022
Topic Review
A Complex Disease: Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) is a complex disease often driven by activating mutations or amplification of the epidermal growth factor receptor (EGFR) gene, which expresses a transmembrane receptor tyrosine kinase. Targeted anti-EGFR treatments include small-molecule tyrosine kinase inhibitors (TKIs), among which gefitinib and erlotinib are the best studied, and their function more often imaged. TKIs block EGFR activation, inducing apoptosis in cancer cells addicted to EGFR signals. 
  • 1.4K
  • 28 Feb 2022
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