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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Synthetic backbone-modified oligomers such as Peptide Nucleic Acids (PNAs), Morpholino Oligonucleotides and Locked Nucleic Acids are designed to recognize and bind to RNA or DNA via standard Watson–Crick base pairing in a sequence-selective fashion, thus preventing translation into the corresponding protein (e.g., Figure 5.94 for PNA). Mixed-base backbone-modified nucleic acids can undergo perfect base-pair recognition when binding to DNA or RNA, and often have enhanced binding affinity and sequence specificity. Thus they are true mimics of natural nucleic acids but can have improved characteristics. A. Schematic diagram showing PNA (an example of a backbone-modified nucleic acid) binding to DNA (Taken from Wu JC., et al. (2017). Recent advances in peptide nucleic acid for cancer bionanotechnology. Acta Pharmacol Sin. 38(6):798‐805. doi:10.1038/aps.2017.33). Copyright © 2017 CPS and SIMM). B. Schematic diagram of a backbone-modified oligomer binding to mRNA and blocking protein production (i.e., the antisense effect).
Lectin
Published in Masahiko Mori, Histochemistry of the Salivary Glands, 2019
Serous cells indicated either none or no traceable staining for PNA, SBA, and WGA lectins; slight binding for Con A, RCA-1, DBA; and a strong reaction for UEA-1 lectin. Mucous cells showed no or very weak staining for PNA, slight reaction for Con A, RCA-1, DBA, and UEA-1, and slight-to moderate binding for SBA and WGA. Sialidase digestion before lectin staining resulted in a dramatically increased PNA staining in both serous and mucous cells, UEA-1 staining of serous cells, and WGA staining of mucous cells. Schulte35 reported that submandibular acinar cells in female mice showed very weak or no staining with PNA; however, after sialidase digestion, acinar cells showed an increased staining for PNA. Acinar cells in serous and mucous cells of human salivary glands probably contain high amounts of terminal GalNAc and Fuc residues. Differences in WGA binding between serous and mucous acinar cells were found. Serous cells failed to stain, irrespective of amylase and sialidase pretreatments, whereas mucous cells stained either with or without enzyme digestions. Mucous cells seem to be more rich in GlcNAc residues, but no or a little GlcNAc is found in serous cells.
Perimenstrual Negative Affect: Development and Testing of an Explanatory Model
Published in Diana L. Taylor, Nancy F. Woods, Menstruation, Health, and Illness, 2019
Diana Taylor, Nancy F. Woods, Martha J. Lentz, Ellen S. Mitchell, Kathryn A. Lee
Most etiological studies emphasize either a single biological or behavioral explanation for PNA and have not differentiated symptomatic women according to specific types of symptoms or severity levels of symptoms. Because menstrual function is associated with ovarian activity, most researchers have focused on the biological etiologies with little attention to psychosocial or environmental variables. A few investigators have suggested that socialization in a traditional feminine role may be linked to menstrual symptoms (Paige, 1973). Moreover, expectations and attitudes about menstruation may socialize a woman to experience (PNA (Brooks-Gunn, Ruble, & Clarke, 1977).
Ineffectiveness of Paramedic Naloxone Administration as a Standalone Metric for Community Opioid Overdoses and the Increasing Use of Naloxone by Community Members
Published in Prehospital Emergency Care, 2023
J. Chris Smith, Wesley S. Burr
Despite PNA’s shortcomings as a standalone metric, it may have value as a component of a larger system. PNA has a function as a secondary marker within a larger metric encompassing paramedic determination (as was done here) to help capture those cases which may be mis-coded. A sudden change in the PNA proportion of total overdoses may also be an important indicator of changes in the local drug market. A sudden increase in PNA proportions could indicate a sudden increase in the potency or contamination of the local drug supply as people who use drugs are not able to manage overdoses themselves, or with friend or family assistance, and turn to emergency services for support. We also note that resuscitation with PNA has previously been associated with an increased risk of drug-related and all-cause mortality in two follow up studies (27, 28), while repeated resuscitations requiring PNA were associated with a two-fold increase in the risk of drug-related mortality (28). In this case, PNA patients, especially repeat PNA patients, may be candidates for more targeted harm reduction interventions.
An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment
Published in Hemoglobin, 2023
Mohammadreza Saeidnia, Pooria Fazeli, Arghavan Farzi, Maryam Atefy Nezhad, Mojtaba Shabani-Borujeni, Mehran Erfani, Gholamhossein Tamaddon, Mehran Karimi
The basis of nuclease-free is peptide nucleic acids (PNAs) [89]. The advantage of nucleobases associated with peptide-like backbone in PNAs is their resistance to nucleases and proteases; moreover, owing to the lack of phosphodiester bond in DNA/PNA structure, it is more stable than DNA/DNA. The complex employs the intrinsic DNA repair machine and triggers high-fidelity DNA repairs by incorporating a short donor DNA template close to the PNA binding site; it should be mentioned that this process does not produce indels. Requiring a delivery transporter is the limitation of this method for acquiring in vivo gene editing solved using nanoparticles. Correcting the IVS-II-654 (C > T) (HBB: c. 316-197 C > T) β-thal mutation in the fetus through DNA/PNA nanoparticles present in utero revealed long-term postnatal improvement [89]. Epigenetic modulation is considered as another genome editing approach that utilizes different mechanisms that cause transcription repression or stimulation via chromatin changes.
The estimation of protein equivalents of total nitrogen in Chinese CAPD patients: an explanatory study
Published in Renal Failure, 2022
Chunyan Su, Tao Wang, Peiyu Wang, Xinhong Lu, Wen Tang
In terms of daily protein intake (DPI) assessment, several guidelines preferred using 3-day dietary records; the other methods, including 24-h food recalls, food frequency questionnaires, and protein equivalent of total nitrogen appearance (PNA), were considered as alternative methods [6–8]. PNA is a common tool used to estimate protein intake and is calculated using urea clearance from 24-h urine and dialysate collection in PD patients. It has been demonstrated that there is a linear relationship between the urea nitrogen appearance (UNA, the urea nitrogen output in urine and dialysate) and the total nitrogen appearance (TNA, the nitrogen output in urine, feces, and dialysate) [9,10]. TNA × 6.25 is considered to represent PNA. Hence, after determining the relationship between UNA and TNA, equations can be derived to estimate PNA from UNA. In patients who are metabolically stable, PNA reflects DPI. It is a simple and easily available method to estimate DPI. Several equations generated from a series of nitrogen balance (NB) studies on European patients undergoing continuous ambulatory peritoneal dialysis (CAPD) [9,11,12] were recommended by the international guidelines to calculate PNA [6,7], especially new Bergstrom formulas [12].