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Topic Review
L-Type Ca2+ Channel Regulation by Calmodulin and CaBP1
L-type voltage-gated Ca2+ channels (CaV1.2 and CaV1.3, called CaV) interact with the Ca2+ sensor proteins, calmodulin (CaM) and Ca2+ binding Protein 1 (CaBP1), that oppositely control Ca2+-dependent channel activity. CaM and CaBP1 can each bind to the IQ-motif within the C-terminal cytosolic domain of CaV, which promotes increased channel open probability under basal conditions. At elevated cytosolic Ca2+ levels (caused by CaV channel opening), Ca2+-bound CaM binding to CaV is essential for promoting rapid Ca2+-dependent channel inactivation (CDI). By contrast, CaV binding to CaBP1 prevents CDI and promotes Ca2+-induced channel opening (called CDF). 
  • 859
  • 15 Dec 2021
Topic Review
Role of miRs in Polyphenol-Mediated Anticancer
The anticancer effects of daily consumption of polyphenols. These dietary polyphenols include chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin, and resveratrol. These polyphenols have similar chemical and biological properties in that they can act as antioxidants and exert the anticancer effects via cell signaling pathways involving their reactive oxygen species (ROS)-scavenging activity. These polyphenols may also act as pro-oxidants under certain conditions, especially at high concentrations. Epigenetic modifications, including dysregulation of noncoding RNAs (ncRNAs) such as microRNAs, long noncoding RNAs, and circular RNAs are now known to be involved in the anticancer effects of polyphenols. These polyphenols can modulate the expression/activity of the component molecules in ROS-scavenger-triggered anticancer pathways (RSTAPs) by increasing the expression of tumor-suppressive ncRNAs and decreasing the expression of oncogenic ncRNAs in general. Multiple ncRNAs are similarly modulated by multiple polyphenols. Many of the targets of ncRNAs affected by these polyphenols are components of RSTAPs. Therefore, ncRNA modulation may enhance the anticancer effects of polyphenols via RSTAPs in an additive or synergistic manner, although other mechanisms may be operating as well.
  • 859
  • 19 Dec 2022
Topic Review
Angiogenesis, Coagulopathy and Endothelial Dysfunction in ANFH
Avascular necrosis of the femoral head (ANFH) is a painful disorder characterized by the cessation of blood supply to the femoral head, leading to its death and subsequent joint collapse. Influenced by several risk factors, including corticosteroid use, excessive alcohol intake, hypercholesterolemia, smoking and some inflammatory disorders, along with cancer, its clinical consequences are thrombus formation due to underlying inflammation and endothelial dysfunction, which collaborates with coagulopathy and impaired angiogenesis. Nonetheless, angiogenesis resolves the obstructed free flow of the blood by providing alternative routes. Clinical manifestations of early stage of ANFH mimic cysts or lesions in subchondral bone, vasculitis and transient osteoporosis of the hip, rendering it difficult to diagnose, complex to understand and complicated to cure. 
  • 859
  • 10 Oct 2023
Topic Review
NUB1 and FAT10 Proteins
The upregulated expression of both NUB1 and FAT10 has been observed in various cancers. NUB1 protein binds to FAT10 non-covalently to promote FAT10 degradation. An overexpressed FAT10 stimulates nuclear factor-kappa β, activates the inflammatory pathways, and induces the proliferation of cancer. The FAT10 protein interacts with the mitotic arrest deficient 2 protein, causing chromosomal instability and breast tumourigenesis. FAT10 binds to the proliferating cell nuclear antigen protein and inhibits the DNA damage repair response. In addition, FAT10 involves epithelial–mesenchymal transition, invasion, apoptosis, and multiplication in hepatocellular carcinoma. 
  • 858
  • 12 Sep 2021
Topic Review
miR-23b-3p, miR-124-3p, and miR-218-5p Regulate Cervical Cancer Progression
In cervical cancer (CC), miR-23b-3p, miR-124-3p, and miR-218-5p have been found to act as tumor suppressors by regulating cellular processes related to progression and metastasis.
  • 858
  • 28 Nov 2022
Topic Review
Parkinson's Disease and COVID-19: Role of TLR4
Parkinson’s disease (PD) is the most common neurodegenerative motor disorder characterized by selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain, depletion of dopamine (DA), and impaired nigrostriatal pathway. The pathological hallmark of PD includes the aggregation and accumulation α-synuclein (α-SYN). Although the precise mechanisms underlying the pathogenesis of PD are still unknown, the activation of toll-like receptors (TLRs), mainly TLR4 and subsequent neuroinflammatory immune response, seem to play a significant role. Mounting evidence suggests that viral infection can concur in precipitation of PD or parkinsonism. The recently identified coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of ongoing pandemic coronavirus disease 2019 (COVID-19), responsible for 160 million cases that led to the death of more than three million individuals worldwide. Studies have reported that many patients with COVID-19 display several neurological manifestations, including acute cerebrovascular diseases, conscious disturbance, and typical motor and non-motor symptoms accompanying PD. The involvement of the TLR4 signaling pathway in mediating the virus entry, and the consequent massive immune and inflammatory response in COVID-19 patients has been recently explored. The strong binding of SARS-CoV-2 spike (S) protein to TLR4 and the possible interaction between SARS-CoV-2 and α-SYN suggest a potential contribute to the acceleration of neuronal death.
  • 857
  • 08 Oct 2021
Topic Review
Cysteinyl Leukotrienes as Multifunctional Inflammation Mediators
Montelukast (MTK)—an antagonist of the cysteinyl leukotrienes receptor 1—is widely used in the management of symptoms among adults and children. Initially described as the slow-reacting substances of anaphylaxis, leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid. Its systemic anti-inflammatory actions, which are particularly important in the brain tissues, are at the onset of various clinical studies focused on the repurposing of this drug for various other diseases, aimed particularly at Alzheimer’s and Parkinson’s diseases.
  • 857
  • 21 Sep 2022
Topic Review
Application of CRISPR/CAS9 in Basic Gastric Cancer Research
Gastric cancer is the subject of clinical and basic studies due to its high incidence and mortality rates worldwide. Due to the diagnosis occurring in advanced stages and the classic treatment methodologies such as gastrectomy and chemotherapy, they are extremely aggressive and limit the quality of life of these patients. CRISPR/Cas9 is a tool that allows gene editing and has been used to explore the functions of genes related to gastric cancer, in addition to being used in the treatment of this neoplasm, greatly increasing our understanding of cancer genomics.
  • 857
  • 28 Nov 2022
Topic Review
Estrogen Receptor Beta
The discovery of the Estrogen Receptor Beta (ERβ) in 1996 opened new perspectives in the diagnostics and therapy of different types of cancer. 
  • 856
  • 19 Feb 2021
Topic Review
Nanoparticles in the Food Industry
Nanoparticles (NPs) are clusters of atoms in the nano-scale. The use of inorganic NPs has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about their impact on human health. As the gut microbiome continues to be increasingly implicated in various gut diseases of unknown etiology, researchers have begun studying the potentially toxic effects of NPs on the gut microbiome and gut barrier. This research has been invaluable in determining the impact of NPs on the intestinal tract ultimately showing that NPs have the potential to contribute to diseases including inflammatory bowel disease and colorectal cancer. With a focus on inorganic nanoparticles, this review presents a discussion of these studies while highlighting NP characteristics, study design, and techniques. Additionally, NP-induced changes to microbial composition are compared with disease-associated alterations in order to elucidate a potential link.
  • 856
  • 11 Mar 2021
Topic Review
Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer
Long non-coding RNAs (lncRNAs) are classified as a group of transcripts that regulate various biological processes, such as RNA processing, epigenetic control, and signaling pathways. According to recent studies, lncRNAs are dysregulated in cancer and play an important role in cancer incidence and spreading. There is also an association between lncRNAs and the overexpression of some tumor-associated proteins, including carbonic anhydrases II, IX, and XII (CA II, CA IX, and CA XII). Therefore, not only CA inhibition but also lncRNA modulation, could represent an attractive strategy for cancer prevention and therapy. Experimental studies have suggested that herbal compounds regulate the expression of many lncRNAs involved in cancer, such as HOTAIR (HOX transcript antisense RNA), H19, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), PCGEM1 (Prostate cancer gene expression marker 1), PVT1, etc. These plant-derived drugs or phytochemicals include resveratrol, curcumin, genistein, quercetin, epigallocatechin-3-galate, camptothecin, and 3,3'-diindolylmethane. More comprehensive information about lncRNA modulation via phytochemicals would be helpful for the administration of new herbal derivatives in cancer therapy.
  • 856
  • 01 Dec 2021
Topic Review
Neglected Human Systemic Mycoses Diagnosis
Systemic mycoses have been viewed as neglected diseases and they are responsible for deaths and disabilities around the world. Rapid, low-cost, simple, highly-specific and sensitive diagnostic tests are critical components of patient care, disease control and active surveillance. 
  • 856
  • 29 Jun 2022
Topic Review
[GADV]-amino Acids and GNC Codons Selected
The genetic code connecting gene with protein is one of the six members (gene, tRNA, genetic code, protein, metabolism, and cell structure) composing the fundamental life system, including the core life system (gene, tRNA, genetic code, and protein). Revealing the origin of the genetic code, one of four members of the core life system might lead to solving the mystery of the origin of life. Therefore, it is quite important to clarify how amino acids and codons were selected among messy organic compounds on primitive Earth and how the first genetic code was established.
  • 856
  • 15 Feb 2023
Topic Review
Vitamin D in Toxins and Aging-Related Compounds Neutralisation
Vitamin D is a micronutrient that is metabolised into a multifunctional secosteroid compound, calcitriol [1,25(OH)2D], essential for the health and survival of humans. Both 25 dihydroxy vitamin D [25(OH)2D: calcifediol] and its hormonal form, 1,25-dihydroxyvitamin D [1,25(OH)2D: calcitriol] are essential for human physiological functions, including damping down inflammation and the excessive intracellular oxidative stresses. The interaction of 1,25(OH)2D with its intracellular (calcitriol)receptors modulates vitamin D–dependent gene transcription and activation of vitamin D-responsive elements, which triggers multiple second messenger systems. Vitamin D controls systemic inflammation, oxidative stress, and mitochondrial respiratory function. Molecular and cellular actions of calcitriol slow down oxidative stress and inflammation, cell and tissue damage, and the aging process, especially when the circulating 25(OH)D concentration is maintained above 50 ng/mL. Whereas, Vitamin D deficiency impairs mitochondrial functions and enhances oxidative stress and systemic inflammation, increases infection-related complications, premature deaths, and accelerates the aging process.  
  • 855
  • 20 Jun 2022
Topic Review
Using GPCRs to Target Ovarian Cancer with Nanomedicines
G protein-coupled receptors (GPCRs) are the largest family of membrane receptors, and many are overexpressed in solid tumors, including ovarian cancer.
  • 855
  • 19 May 2022
Topic Review
TATDN2
Replicative DNA polymerases are blocked by nearly all types of DNA damage. The resulting DNA replication stress threatens genome stability. DNA replication stress is also caused by depletion of nucleotide pools, DNA polymerase inhibitors, and DNA sequences or structures that are difficult to replicate. Replication stress triggers complex cellular responses that include cell cycle arrest, replication fork collapse to one-ended DNA double-strand breaks, induction of DNA repair, and programmed cell death after excessive damage. Replication stress caused by specific structures (e.g., G-rich sequences that form G-quadruplexes) is localized but occurs during the S phase of every cell division.
  • 854
  • 06 Dec 2023
Topic Review
Myelin Basic Protein Interaction Landscape
Intrinsically disordered myelin basic protein (MBP) is one of the key autoantigens in autoimmune neurodegeneration and multiple sclerosis particularly. MBP is highly positively charged and lacks a distinct structure in solution, and therefore its intracellular partners are still mostly enigmatic. Here authors used combination of formaldehyde-induced cross-linking followed by immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the interaction network of MBP in mammalian cells and provide the list of potential MBP interacting proteins.
  • 852
  • 15 Nov 2021
Topic Review
Inorganic SOD1 Inhibitors with Anti-Cancer Prospects
For eukaryotic cells, reactive oxygen species (ROS) encompass a group of molecules derived from oxygen. Due to the well-established role of ROS in cell signaling, cancer cells always have higher levels of endogenous ROS to enhance rapid cell growth and proliferation through the mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase 1/2 (ERK1/2), phosphoinositide-3-kinase (PI3K)/Akt, nuclear factor-κB (NF-κB), and hypoxia-sensitive α (HIF1α) pathways. Evaluated ROS have frequently been observed in various cancers, which activate multiple pro-tumourigenic signaling, and induce survival and proliferation of cancer cells. Hydrogen peroxide and superoxide anion are the most important redox signaling agents in cancer cells, whose homeostasis is maintained by dozens of growth factors, cytokines and antioxidant enzymes. Therefore, antioxidant enzymes, especially Cu/Zn superoxide dismutase (SOD1), tend to have higher activities to maintain the homeostasis of ROS in cancer cells. We can inhibit the activity of SOD1 using copper chelators to kill cancer cells. 
  • 852
  • 13 Jan 2022
Topic Review
Vanadium Effects on Lipid Peroxidation and Disease Processes
Lipid peroxidation (LPO), a process that affects human health, can be induced by exposure to vanadium salts and compounds. LPO is often exacerbated by oxidation stress, with some forms of vanadium providing protective effects. The LPO reaction involves the oxidation of the alkene bonds, primarily in polyunsaturated fatty acids, in a chain reaction to form radical and reactive oxygen species (ROS). The important question is which radical starts the chain first. On the one hand, a radical is needed (oxidative stress environment) while on the other hand, LPO amplifies and contributes to changing the redox state towards oxidation (what was called oxidative stress). 
  • 852
  • 31 Mar 2023
Topic Review
Dysregulated JNK Signaling Pathway in Human Diseases
JNK is named after c-Jun N-terminal kinase, as it is responsible for phosphorylating c-Jun. As a member of the mitogen-activated protein kinase (MAPK) family, JNK is also known as stress-activated kinase (SAPK) because it can be activated by extracellular stresses including growth factor, UV irradiation, and virus infection. Functionally, JNK regulates various cell behaviors such as cell differentiation, proliferation, survival, and metabolic reprogramming. Dysregulated JNK signaling contributes to several types of human diseases.
  • 852
  • 11 Mar 2024
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