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Topic Review
Innate Immunity to Tick-Borne Pathogens
Tick borne pathogens, such as Anaplasma spp., Ehrlichia spp., Rickettsia spp., Babesia and Theileria sensu stricto species, cause infectious diseases both in animals and humans. Different types of immune effector mechanisms could be induced in hosts by these microorganisms. The components of innate immunity, such as natural killer cells, complement proteins, macrophages, dendritic cells and tumor necrosis factor alpha, cause a rapid and intense protection for the acute phase of infectious diseases. Moreover, the onset of a pro-inflammatory state occurs upon the activation of the inflammasome, a protein scaffold with a key-role in host defense mechanism, regulating the action of caspase-1 and the maturation of interleukin-1β and IL-18 into bioactive molecules. Innate immunity is activated immediately after the infection and inflammasome-mediated changes in the pro-inflammatory cytokines at systemic and intracellular levels can be detected as early as on days 2–5 after tick bite. The knowledge of the innate immunity mechanisms could lead to the development of new methods of emergency diagnosis and prevention of tick-borne infections.
  • 1.3K
  • 18 Dec 2020
Topic Review
Aberrant BMP2 Signaling
The most common bone disease in humans is osteoporosis (OP). Current therapeutics targeting OP have several negative side effects. Bone morphogenetic protein 2 (BMP2) is a potent growth factor that is known to activate both osteoblasts and osteoclasts. It completes these actions through both SMAD-dependent and SMAD-independent signaling. A novel interaction between the BMP type Ia receptor (BMPRIa) and casein kinase II (CK2) was discovered, and several CK2 phosphorylation sites were identified. A corresponding blocking peptide (named CK2.3) was designed to further elucidate the phosphorylation site’s function. Previously, CK2.3 demonstrated an increased osteoblast activity and decreased osteoclast activity in a variety of animal models, cell lines, and isolated human osteoblasts. It is hypothesized that CK2.3 completes these actions through the BMP signaling pathway. Furthermore, it was recently discovered that BMP2 did not elicit an osteogenic response in osteoblasts from patients diagnosed with OP, while CK2.3 did.
  • 1.3K
  • 26 Oct 2020
Topic Review
Talazoparib and Niraparib
Niraparib (MK-4827) inhibits PARP1 and PARP2. It was approved by the U.S. Food and Drug Administration (FDA) in March 2017 indicated for the therapy of adult patients with ovarian, fallopian tube and peritoneal neoplasms. Talazoparib (BMN 673) is a potent and selective inhibitor of PARP1 and PARP2 used at lower concentrations than previous generations of PARP inhibitors. The FDA approved Talazoparib in October 2018 for patients with germline BRCA-mutated, HER2-negative breast cancer. Poly (ADP-ribose) polymerases (PARP) play an essential role in different cellular processes, including several pathways of DNA repair. PARP inhibitors (PARPi) are able to impair DNA damage repair by non-homologous end joining (NHEJ). This effect depends on the cell´s ability to compensate for the inhibition of PARP-mediated pathways by other repair pathways. PARPi especially induce cell death in cancer cells with a lack of PARP-independent DNA repair pathways.
  • 1.3K
  • 25 Jun 2021
Topic Review
Large Rab GTPases
Rab GTPases are major coordinators of intracellular membrane trafficking, including vesicle transport, membrane fission, tethering, docking, and fusion events. Rab GTPases are roughly divided into two groups: conventional “small” Rab GTPases and atypical “large” Rab GTPases that have been recently reported. Some members of large Rab GTPases in mammals include Rab44, Rab45/RASEF, and Rab46. The genes of these large Rab GTPases commonly encode an amino-terminal EF-hand domain, coiled-coil domain, and the carboxyl-terminal Rab GTPase domain. A common feature of large Rab GTPases is that they express several isoforms in cells. For instance, Rab44’s two isoforms have similar functions, but exhibit differential localization. The long form of Rab45 (Rab45-L) is abundantly distributed in epithelial cells. The short form of Rab45 (Rab45-S) is predominantly present in the testes. Both Rab46 (CRACR2A-L) and the short isoform lacking the Rab domain (CRACR2A-S) are expressed in T cells, whereas Rab46 is only distributed in endothelial cells. Although evidence regarding the function of large Rab GTPases has been accumulating recently, there are only a limited number of studies. Here, we report the recent findings on the large Rab GTPase family concerning their function in membrane trafficking, cell differentiation, related diseases, and knockout mouse phenotypes.
  • 1.3K
  • 16 Aug 2021
Topic Review
Sources of Reactive Oxygen Species
Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the cellular anti-oxidant defense mechanisms, plays a critical role in the pathogenesis of various human diseases. ROS are either produced through cellular processes or environmental factors. Of note, oxidative stress has been described as a secondary effect within the pathology of several rare monogenic diseases and sometimes been called a common denominator. 
  • 1.3K
  • 26 Feb 2024
Topic Review
Vitamin D and Primary Ciliary Dyskinesia
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. Low plasmatic level of this vitamin is present in the PCD population. The utility of vitamin D supplementation may be essential in this group of individuals.
  • 1.3K
  • 04 Nov 2021
Topic Review
Polyphenols Nano Formulations
Polyphenols are phytochemical with potent antioxidant and antiinflammatory activities which are tremendously of important to fight premature aging, infections, cancers and other related chronic inflammatory diseases. Nanoencapsulation of these natural and functional biocompounds is useful to increase the bioavailability and efficiency of polyphenols, which can be further used as adjuvant therapeutics.
  • 1.3K
  • 26 Nov 2020
Topic Review
Tellurium: Its Influence on Organisms
Tellurium (Te) is a member of the chalcogen group, which includes oxygen, sulphur, selenium (Se) and polonium . The first three members of the chalcogen group have crucial functions in biochemistry, biology and medicine, whereas Te is a strange element with no apparent role in biological systems. Moreover, it belongs to the group of very few elements in the Periodic Table that have been almost completely ignored.
  • 1.3K
  • 09 Jul 2021
Topic Review
Hydroxy Fatty Acid
Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with interesting physiological functions in mammals. Despite their structural diversity and links with nuclear factor erythroid 2-related factor 2 (NRF2) biosynthesis, FAHFAs are less explored as NRF2 activators. 
  • 1.3K
  • 06 Aug 2021
Topic Review
Preventing and Treating Cancer by Green Tea Catechins
Green tea’s (Camellia sinensis) anticancer and anti-inflammatory effects are well-known. Catechins are the most effective antioxidants among the physiologically active compounds found in Camellia sinesis. Catechins have the ability to effectively neutralize reactive oxygen species. The catechin derivatives of green tea include epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG has the greatest anti-inflammatory and anticancer potential. Notably, catechins in green tea have been explored for their ability to prevent a variety of cancers.
  • 1.3K
  • 21 Sep 2022
Topic Review
Human Pluripotent Stem Cell-derived Cardiomyocytes
Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the cardiovascular system, including AF; however, a large group of lncRNAs is not conserved between mouse and human. Furthermore, AF has complex networks showing variations in mechanisms in different species, making it challenging to utilize conventional animal models to investigate the functional roles and potential therapeutic benefits of lncRNAs for AF. Fortunately, pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) offer a reliable platform to study lncRNA functions in AF because of certain electrophysiological and molecular similarities with native human CMs.
  • 1.3K
  • 27 Oct 2020
Topic Review
Topical Insulin Delivery
Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. 
  • 1.3K
  • 13 Sep 2021
Topic Review
Gap Junctions in Atrial Fibrillation
Atrial fibrillation (AF) represents the most common type of clinical cardiac arrhythmia worldwide and contributes to substantial morbidity, mortality and socioeconomic burden. Aggregating evidence highlights the strong genetic basis of AF. In addition to chromosomal abnormalities, pathogenic mutations in over 50 genes have been causally linked to AF, of which the majority encode ion channels, cardiac structural proteins, transcription factors and gap junction channels. In the heart, gap junctions comprised of connexins (Cxs) form intercellular pathways responsible for electrical coupling and rapid coordinated action potential propagation between adjacent cardiomyocytes. Among the 21 isoforms of connexins already identified in the mammal genomes, 5 isoforms (Cx37, Cx40, Cx43, Cx45 and Cx46) are expressed in human heart. Abnormal electrical coupling between cardiomyocytes caused by structural remodeling of gap junction channels (alterations in connexin distribution and protein levels) has been associated with enhanced susceptibility to AF and recent studies have revealed multiple causative mutations or polymorphisms in 4 isoforms of connexins predisposing to AF.
  • 1.3K
  • 11 Apr 2022
Topic Review
Omega-3 Fatty Acids on Insulin Resistance
Insulin resistance is a critical pathophysiological process in the onset and advancement of type 2 diabetes mellitus. It is well-recognized that alterations in the metabolism of lipids and aberrant fat buildup effectively trigger the development of resistance to insulin. Adjusting one’s eating habits and managing weight appropriately are crucial for treating, controlling, and reducing the risk of T2DM because obesity and a lack of physical exercise are the primary factors responsible for the worldwide rise in T2DM. Omega-3 fatty acid is one of the polyunsaturated fatty acids (PUFA) that include long-chain omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, commonly found in fish oils.
  • 1.3K
  • 21 Jun 2023
Topic Review
Nucleases and Co-Factors in DNA Replication Stress Responses
DNA replication stress is a constant threat that cells must manage to proliferate and maintain genome integrity. DNA replication stress responses, a subset of the broader DNA damage response (DDR), operate when the DNA replication machinery (replisome) is blocked or replication forks collapse during S phase. There are many sources of replication stress, such as DNA lesions caused by endogenous and exogenous agents including commonly used cancer therapeutics, and difficult-to-replicate DNA sequences comprising fragile sites, G-quadraplex DNA, hairpins at trinucleotide repeats, and telomeres. Replication stress is also a consequence of conflicts between opposing transcription and replication, and oncogenic stress which dysregulates replication origin firing and fork progression. Cells initially respond to replication stress by protecting blocked replisomes, but if the offending problem (e.g., DNA damage) is not bypassed or resolved in a timely manner, forks may be cleaved by nucleases, inducing a DNA double-strand break (DSB) and providing a means to accurately restart stalled forks via homologous recombination. However, DSBs pose their own risks to genome stability if left unrepaired or misrepaired.  
  • 1.3K
  • 29 Mar 2022
Topic Review
Gap Junction Channel
In most tissues, cells in contact with each other exchange cytosolic molecules of low molecular weight via channels aggregated at gap junctions. Gap junction mediated cell-to-cell communication allows neighboring cells to coordinate and regulate many functional activities in mature and developing organs. A gap junction channel is made of the interaction of two hemichannels (connexons/innexons) that form a hydrophilic pathway across the two apposed plasma membranes and the extracellular space (gap). Each connexon/innexon is an oligomer of six proteins (connexins/innexins) that span the plasma membrane and create a hydrophilic pore insulated from lipid bilayer and extracellular medium (Rev. in: Peracchia, C., Gap junction stucture and chemical regulation. Direct calmodulin role in cell-to-cell channel gating. Academic Press. An imprint of Elsevier: London, UK, 2019). Gap junction channels have been thought to possess as many as four types of gates: fast transjunctional voltage (Vj) gate, slow Vj-gate, chemical gate and gate sensitive to membrane potential (Vm). However, since the behavior of the slow Vj-gate and the Vm-sensitive is the same as that of the chemical gate, most likely these gates are the same. We have named this gate “chemical/slow gate” (Peracchia, C. Calmodulin-mediated regulation of gap junction channels. Int. J. Mol. Sci. 2020, 21, 485). In 2000, we proposed a calmodulin (CaM)-mediated “cork-type” gating model. The model proposes two mechanisms. One, “Ca-CaM-Cork”, envisions physical blockage of the channel’s mouth by a CaM lobe (N-lobe?), likely to be combined with conformational connexin changes induced by Ca2+-CaM binding to connexin sites. The other, “CaM-Cork”, also proposes a physical blockage of the channel’s mouth by a CaM lobe, but without calcium-ctivation. The first is only reversed by the return of intracellular Ca2+ concentration ([Ca2+]i) to resting values. The latter is reversed by Vj positive at the gated side (Peracchia, C. Calmodulin-Cork model of gap junction channel gating. - One molecule, two mechanisms. Int. J. Mol. Sci. 2020, 21, 4938). Evidence that gap junction mediated cell communication is finely regulated by nanomolar [Ca2+]i via the direct action of Ca2+-CaM indicates that gap junction channel gating is not just a safety mechanism for protecting cells from damaged/dead neighbors (healing-over). Rather, it is also a mechanism designed to finely modulate cell–cell exchange of small molecules. In summary: At resting [Ca2+]i, (<50nM) some channels are spontaneously closed by the CaM-Cork gating mechanism. With moderate [Ca2+]i rise (50–100 nM, the CaMKII cascade may be activated causing channels closed by the CaM-Cork mechanism to open. With greater [Ca2+]i rise (>100 nM), the channels start closing by the Ca-CaM-Cork mechanism. CaM lobe channel mouth plugging is likely to include connexin conformational changes. CaM-Cork gated channels could be reopened by Vj positive at gated side, but since they would close at the negative side no Gj change would occur. This is not the case with heterotypic channels between wild-type connexins paired with more gating-sensitive mutants. Most Ca-CaM-Cork gated channels reopen with a drop in [Ca2+]i to resting values (<50 nM). However, with prolonged exposure to high [Ca2+]i, channel gating may not be reversible. Many questions still need to be answered in terms of molecular details, such as: Is CaM anchored to the NT or the CL2 domain? Is CaM anchored to connexins by the C-lobe or the N-lobe? Is the gating lobe the N-lobe or the C-lobe? Does the gating lobe bind to the CL2 or the NT CaM binding site? Are all of the CaMs anchored to a connexon Ca2+-activated? If so, how many lobes gate the channel? Does CaM activation cause connexin conformational changes?
  • 1.3K
  • 17 Jul 2020
Topic Review
LncRNAs
Chemo and radiation therapies are the most commonly used therapies for cancer, but they can induce DNA damage, resulting in the apoptosis of host cells. DNA double-stranded breaks (DSBs) are the most lethal form of DNA damage in cells, which are constantly caused by a wide variety of genotoxic agents, both environmentally and endogenously. To maintain genomic integrity, eukaryotic organisms have developed a complex mechanism for the repair of DNA damage. Researches reported that many cellular long noncoding RNAs (lncRNAs) were involved in the response of DNA damage. The roles of lncRNAs in DNA damage response can be regulated by the dynamic modification of N6-adenosine methylation (m6A). The cellular accumulation of DNA damage can result in various diseases, including cancers. Additionally, lncRNAs also play roles in controlling the gene expression and regulation of autophagy, which are indirectly involved with individual development. The dysregulation of these functions can facilitate human tumorigenesis. In this review, we summarized the origin and overview function of lncRNAs and highlighted the roles of lncRNAs involved in the repair of DNA damage.
  • 1.3K
  • 03 Feb 2021
Topic Review
Marine Algae Polysaccharide in Gut Microbiota
Cardiovascular disease (CVD) is the number one cause of death worldwide. Evidence has demonstrated an association between the gut microbiota and CVD, including heart failure, cerebrovascular illness, hypertension, and stroke. Marine algal polysaccharides (MAPs) are valuable natural sources of diverse bioactive compounds. MAPs have many pharmaceutical activities, including antioxidant, anti-inflammatory, immunomodulatory, and antidiabetic effects. 
  • 1.3K
  • 28 Nov 2022
Topic Review
Phytochemicals in Redox Homeostasis
Redox homeostasis, a dynamic process ensuring a balance between cellular oxidizing and reducing reactions, is crucial for maintaining healthy cellular physiology and regulating many biological processes, requiring continuous monitoring and fine-tuning. Reactive species play a critical role in intra/intercellular signaling, and each cell has a specific system guarding cellular redox homeostasis. Reactive oxygen species (ROS) signaling and oxidative stress are involved in cancer initiation and progression.
  • 1.3K
  • 24 Apr 2023
Topic Review
C-type Lectin CD209L/L-SIGN and CD209/DC-SIGN
COVID-19 pandemic continues to pose a serious threat to global public health with overwhelming worldwide socio-economic disruption. SARS-CoV-2, the viral agent of COVID-19, uses its surface glycoprotein Spike (S) for host cell attachment and entry. The emerging picture of pathogenesis of SARS-CoV-2 demonstrates that S protein, in addition, to ACE2, interacts with the carbohydrate recognition domain (CRD) of C-type lectin receptors, CD209L and CD209. Recognition of CD209L and CD209 which are widely expressed in SARS-CoV-2 target organs can facilitate entry and transmission leading to dysregulation of the host immune response and other major organs including, cardiovascular system. Establishing a comprehensive map of the SARS-CoV-2 interaction with CD209 family proteins, and their roles in transmission and pathogenesis can provide new insights into host-pathogen interaction with implications in therapies and vaccine development. 
  • 1.3K
  • 13 Jan 2021
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