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Topic Review
Implications of siRNA Therapy in Bone Health
The global statistics of bone disorders, skeletal defects, and fractures are frightening. Several therapeutic strategies are being used to fix them; however, RNAi-based siRNA therapy is starting to prove to be a promising approach for the prevention of bone disorders because of its advanced capabilities to deliver siRNA or siRNA drug conjugate to the target tissue. Despite its ‘bench-to-bedside’ usefulness and approval by food and drug administration for five siRNA-based therapeutic medicines: Patisiran, Vutrisiran, Inclisiran, Lumasiran, and Givosiran, its use for the other diseases still remains to be resolved. By correcting the complications and complexities involved in siRNA delivery for its sustained release, better absorption, and toxicity-free activity, siRNA therapy can be harnessed as an experimental tool for the prevention of complex and undruggable diseases with a personalized medicine approach.
  • 759
  • 20 Feb 2024
Topic Review
Dynamic Changes in DNA Methylation in Brain Development
DNA cytosine methylation is a principal epigenetic mechanism underlying transcription during development and aging. Growing evidence suggests that DNA methylation plays a critical role in brain function, including neurogenesis, neuronal differentiation, synaptogenesis, learning, and memory.
  • 759
  • 22 Feb 2023
Topic Review
PGC1α
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a protein that promotes transcription of numerous genes, particularly those responsible for the regulation of mitochondrial biogenesis. Evidence for a key role of PGC1α in bone metabolism is very recent. In vivo studies showed that PGC1α deletion negatively affects cortical thickness, trabecular organization and resistance to flexion, resulting in increased risk of fracture. 
  • 758
  • 18 May 2021
Topic Review
Mechanisms of Polyphenols as Treatment Against Neuroblastoma
Neuroblastoma (NB) is an extracranial tumor of the peripheral nervous system arising from neural crest cells. It is the most common malignancy in infants and the most common extracranial solid tumor in children. The treatment for high-risk NB involves chemotherapy and surgical resection followed by high-dose chemotherapy with autologous stem-cell rescue and radiation treatment. However, those with high-risk NB are susceptible to relapse and the long-term side effects of standard chemotherapy. Polyphenols, including the sub-class of flavonoids, contain more than one aromatic ring with hydroxyl groups.
  • 758
  • 06 Apr 2023
Topic Review
Self-Defense Mechanism in Rice to Salinity
Salinity has complex effects on plants, impacting many cellular and physiological systems. Plant roots absorb elevated sodium ions (Na+) in the soil. Elevated concentrations of Na+ alter the normal balance of ions within plant cells.
  • 758
  • 26 Mar 2024
Topic Review
Human Triosephosphate Isomerase as Potential Target in Cancer
Cancer involves a series of diseases where cellular growth is not controlled. Cancer is a leading cause of death worldwide, and the burden of cancer incidence and mortality is rapidly growing, mainly in developing countries. Many drugs are currently used, from chemotherapeutic agents to immunotherapy, among others, along with organ transplantation. Treatments can cause severe side effects, including remission and progression of the disease with serious consequences. Increased glycolytic activity is characteristic of cancer cells. Triosephosphate isomerase is essential for net ATP production in the glycolytic pathway.
  • 757
  • 19 Oct 2023
Topic Review
Aryl Hydrocarbon Receptor Signaling
The aryl hydrocarbon receptor (AHR) is a markedly established regulator of a plethora of cellular and molecular processes. Its initial role in the detoxification of xenobiotic compounds has been partially overshadowed by its involvement in homeostatic and organ physiology processes. In fact, the discovery of its ability to bind specific target regulatory sequences has allowed for the understanding of how AHR modulates such processes. Thereby, AHR presents functions in transcriptional regulation, chromatin architecture modifications and participation in different key signaling pathways. Interestingly, such fields of influence end up affecting organ and tissue homeostasis, including regenerative response both to endogenous and exogenous stimuli. Beyond the role of AHR in transcriptional regulation, its implication in multiple signaling pathways has built a field of study regarding its participation in the control and maintenance of different physiological and pathological processes. The variety of responses resulting from AHR activation may be due to the different interactions of the receptor with other proteins or transcriptional cofactors. Therefore, numerous proteins affecting AHR activity and vice versa have been described over the years, constituting a solid trend in cell signaling.
  • 756
  • 14 Dec 2022
Topic Review
Viral Non-Coding RNAs as Transcriptional Weapons
Viral non-coding RNAs are gaining much value and interest for the potential impact played in host gene regulation, acting as fine tuners of host cellular defense mechanisms. Several viruses are able to produce v-ncRNAs that are frequently expressed at high copy numbers in infected cells. V-ncRNAs are capable of interacting with different host cell pathways leading to the modulation of different biological processes including: 1. regulation of viral and host gene expression; 2. cell survival; 3. viral infection/replication; 4. cell transformation; 5 virus proliferation/propagation . On the other hand, host cells regulate their own ncRNAs expression in order to activate defense mechanisms against virus infection.
  • 756
  • 15 Dec 2022
Topic Review
Master Antioxidant Pathway Induced in Oxidative Stress Condition
Cells need an antioxidant defense barrier against oxidizing molecules to establish cell hemostasis. Antioxidants are nucleophiles that have a high affinity to react with electrophilic reactive species and neutralize them. Glutathione (GSH), as the most abundant endogenous antioxidant molecule, displays a specific role in the oxidative response. It can effectively eliminate ROS and decreases the generation of the oxidative signal. In this process, GSH donates an electron to form two oxidized GSH (GSSG).
  • 756
  • 03 Apr 2023
Topic Review
Battling Chemoresistance in Cancer
Chemoresistance remains a lethal challenge in the realm of cancer biology and clinics. Various determinants with their modes of action have been reported with clinical implications. However, many patients regrettably die due to chemoresistance-induced failure in treatment.
  • 755
  • 22 Sep 2021
Topic Review
Ribosome and Ribosome Biogenesis
The ribosome represents a complex macromolecular structure composed of RNA and proteins, interacting through an intricate and interlinked network to sustain its fundamental ancient functionalities. The synthesis of ribosomes entails a sophisticated and energetically demanding process that induced cells during their evolution to select a range of stringent control mechanisms across diverse cellular signalling pathways. In actively dividing cells, there's a stimulation to generate new ribosomes to cope with heightened biosynthetic requirements. Nevertheless, when signals of cellular stress emerge or disruptions arise within the ribosome biogenesis process, there is a rapid cessation of rRNA transcription, leading to interruptions at various stages of ribosome assembly. The impairment of the accurate construction and function of ribosomes characterises a range of dysfunctions commonly identified as ribosomopathies.
  • 755
  • 08 Nov 2023
Topic Review
Mitochondrial Calcium in Pancreatic β-Cell
β-cell mitochondria sense and shape calcium signals, linking the metabolism of glucose and other secretagogues to the generation of signals that promote insulin secretion during nutrient stimulation.
  • 754
  • 23 Mar 2021
Topic Review
Curcumin and Nano-Curcumin Mitigate Neurotoxicity
Curcumin (CUR) is a hydrophobic polyphenolic compound found natively in turmeric. It exhibits antioxidant, antimicrobial, anti-inflammatory, pulmoprotective, anti-diabetic, hepatoprotective, nephroprotective, and antitumor actions. In addition to these pharmacological effects, CUR possesses neuroprotective activity where it protected the brain against oxidative injury induced by heavy metals. 
  • 754
  • 27 Oct 2021
Topic Review
Early OA Stage Like Response of synovial fibroblasts
As events triggering early osteoarthritis onset can be related to mechanical stress and proinflammatory signaling, the e ffect of diff erent mechanical strain protocols on the expression of proinflammatory genes, as well as extracellular matrix remodelling in human synovial fibroblasts are of interest. Three distinct models of tensile stretching were analyzed: static isotropic tensile strain at 0 Hz, 16% tension for 48 hours; short-term high-frequency cyclic tension at 1 Hz, 10% tension for 4 hours; and dynamic tensile stretching for 48 hours, consisting of two blocks of moderate stretching at 0.2 Hz, 2%, advanced stretching at 0.5 Hz, 15%, or a combination of both. General signs of inflammation were present after static isotropic tension, whereas short-term high-frequency cyclic tension showed increased levels of IL-6 paired with diminished levels of IL-1 . Reduced inflammatory e ffects of TNF- , IL-6, and IL-1 were observed when exposed to advanced stretching. Long-term tensile strain induced extracellular matrix remodelling at the gene and protein levels. While hyaluronan acid synthesis was increased with static tensile strain, dynamic tensile stretching had a reducing effect.It is suggested that proinflammatory markers are activated by mechanical strain as seen in static isotropic tension and short-term high-frequency tensile strain, whereas long-term exposure induced extracellular matrix remodelling processes.
  • 753
  • 24 Jun 2020
Topic Review
Metadherin and RKIP
Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF-κκB. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of RKIP gene in human cancers is not well understood. In this study, we suggested a possible transcription mechanism for the regulation of RKIP in human cancer cells. We found that Metadherin (MTDH) significantly repressed the transcriptional activity of RKIP gene. 
  • 753
  • 15 Apr 2021
Topic Review
THUMP-Related tRNA Modification Enzymes
The existence of the thiouridine synthetase, methyltransferase and pseudouridine synthase (THUMP) domain was originally predicted by a bioinformatic study. Since the prediction of the THUMP domain, many tRNA modification enzymes containing the THUMP domain have been identified. According to their enzymatic activity, THUMP-related tRNA modification enzymes can be classified into five types, namely 4-thiouridine synthetase, deaminase, methyltransferase, a partner protein of acetyltransferase and pseudouridine synthase. Biochemical, biophysical and structural studies of tRNA 4-thiouridine synthetase, tRNA methyltransferases and tRNA deaminase have established the concept that the THUMP domain captures the 3′-end of RNA (in the case of tRNA, the CCA-terminus).
  • 753
  • 15 Feb 2023
Topic Review
Nonreceptor Tyrosine Kinase Ack1
The nonreceptor tyrosine kinase (NRTK) Ack1 comprises a distinct arrangement of non-catalytic modules. Its SH3 domain has a C-terminal to the kinase domain (SH1), in contrast to the typical SH3-SH2-SH1 layout in NRTKs. The Ack1 is the only protein that shares a region of high homology to the tumor suppressor protein Mig6, a modulator of EGFR. The vertebrate Acks make up the only tyrosine kinase (TK) family known to carry a UBA domain. The GTPase binding and SAM domains are also uncommon in the NRTKs. In addition to being a downstream effector of receptor tyrosine kinases (RTKs) and integrins, Ack1 can act as an epigenetic regulator, modulate the degradation of the epidermal growth factor receptor (EGFR), confer drug resistance, and mediate the progression of hormone-sensitive tumors. 
  • 753
  • 18 Apr 2023
Topic Review
CRISPR/Cas9 Landscape
CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 is a unique genome editing tool that can be easily used in a wide range of applications, including functional genomics, transcriptomics, epigenetics, biotechnology, plant engineering, livestock breeding, gene therapy, diagnostics, and so on.
  • 753
  • 16 Nov 2023
Topic Review
Dry Ethanol Extracts from Koelreuteria paniculata Laxm
Koelreuteria paniculata Laxm. is used in traditional medicine and has various established biological activities, however, the species is considered to be a potentially invasive alien tree species for Bulgarian flora. However, there is still much to be studied about the phytochemical and biological characteristics of the species. 
  • 752
  • 28 Jan 2022
Topic Review
Inflammation, Mitochondria and Natural Compounds
Human diseases are characterized by the perpetuation of an inflammatory condition in which the levels of Reactive Oxygen Species (ROS) are quite high. Excessive ROS production leads to DNA damage, protein carbonylation and lipid peroxidation, conditions that lead to a worsening of inflammatory disorders. In particular, compromised mitochondria sustain a stressful condition in the cell, such that mitochondrial dysfunctions become pathogenic, causing human disorders related to inflammatory reactions. Indeed, the triggered inflammation loses its beneficial properties and turns harmful if dysregulation and dysfunctions are not addressed. Thus, reducing oxidative stress with ROS scavenger compounds has proven to be a successful approach to reducing inflammation. Among these, natural compounds, in particular, polyphenols, alkaloids and coenzyme Q10, thanks to their antioxidant properties, are capable of inhibiting the activation of NF-κB and the expression of target genes, including those involved in inflammation.
  • 752
  • 30 Mar 2023
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