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European Journal of Medicinal Chemistry Jun 2024A new series of racemic fluorescent octahydrophenazines (rac-PZ1-11) have been designed and synthesized via the efficient nucleophilic aromatic substitution (SAr) of...
A new series of racemic fluorescent octahydrophenazines (rac-PZ1-11) have been designed and synthesized via the efficient nucleophilic aromatic substitution (SAr) of tetrafluorobenzenedinitriles (1a-c) and racemic cyclohexane-1,2-diamines (rac-2a and b). The bioactivities of these racemic rac-PZs (20 μM) against herpes simplex virus type-1 (HSV-1) were evaluated by the relative cell viability of Vero cells infected with HSV-1. It was found that rac-PZ3 shows much higher anti-HSV-1 activity than others, with EC = 9.2 ± 1.4 μM. Further investigation into the anti-HSV activities of rac-PZ3 and its enantiomers RR- and SS-PZ3 indicates that rac-PZ3 can also efficiently inhibit HSV-2 and even ACV-resistant HSV-2 (EC = 11.0 ± 2.3 and 14.9 ± 2.8 μM, respectively), SS-PZ3 has better activities against HSV-1, HSV-2 and ACV-resistant HSV-2 (EC = 4.1 ± 1.1, 5.8 ± 1.0 and 7.9 ± 1.2 μM, respectively), but RR-PZ3 has almost no antiviral activities. The primary mechanism study indicates that rac-PZ3 efficiently reverses the HSV-1/2-induced cytopathic effect and suppresses the expression of viral mRNA and proteins. In addition, rac-, RR- and SS-PZ3 possess excellent fluorescence properties with almost the same emission wavelength and high fluorescence quantum yields (Φ = 90.3-92.3 % in cyclohexane solutions and 54.4-57.3 % in solids) and can target endoplasmic reticulum and cell membrane. The efficient anti-HSV bioactivities and excellent fluorescence of PZ3 prove its potential applications in antiviral therapy and biological imaging.
PubMed: 38896994
DOI: 10.1016/j.ejmech.2024.116580 -
Molecules (Basel, Switzerland) Jun 2024In this paper, urethane-based acrylates (UA) were prepared via an environmentally friendly non-isocyanate route. Isophorone diamine (IPDA) reacted with ethylene...
In this paper, urethane-based acrylates (UA) were prepared via an environmentally friendly non-isocyanate route. Isophorone diamine (IPDA) reacted with ethylene carbonate (EC), producing carbamate containing amine and hydroxyl groups, which further reacted with neopentyl glycol diacrylate (NPGDA) by aza Michael addition, forming UA. The structures of the obtained intermediates and UA were characterized by H NMR and electrospray ionization high-resolution mass spectrometry (ESI-HRMS). The photopolymerization kinetics of UA were investigated by infrared spectroscopy. The composite with obtained UA can be UV cured quickly to form a transparent film with a tensile strength of 21 MPa and elongation at break of 16%. After UV curing, the mono-functional urethane acrylate was copolymerized into the cross-linked network in the form of side chains. The hydroxyl and carbamate bonds on the side chains have high mobility, which make them easy to form stronger dynamic hydrogen bonds during the tensile process, giving the material a higher tensile strength and elongation at break. Therefore, the hydrogen bonding model of a cross-linked network is proposed. The composite with UA can be 3D printed into models.
PubMed: 38893514
DOI: 10.3390/molecules29112639 -
International Journal of Molecular... Jun 2024Phenotypic susceptibility testing of the complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing...
Phenotypic susceptibility testing of the complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials-isoniazid, rifampin, ethambutol, and pyrazinamide-for MTBC isolates tested between the years 2018-2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid, rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid, rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks.
Topics: Whole Genome Sequencing; Mycobacterium tuberculosis; Antitubercular Agents; Humans; Microbial Sensitivity Tests; Retrospective Studies; Drug Resistance, Bacterial; Genome, Bacterial; Ethambutol; Isoniazid; Pyrazinamide; Tuberculosis; Rifampin
PubMed: 38892433
DOI: 10.3390/ijms25116245 -
Polymers Jun 2024With the increasing demand for innovative electronic products, LED transparent screens are gradually entering the public eye. Polyimide (PI) materials combine high...
With the increasing demand for innovative electronic products, LED transparent screens are gradually entering the public eye. Polyimide (PI) materials combine high temperature resistance and high transparency, which can be used to prepare flexible copper-clad laminate substrates. The physical and chemical properties of PI materials differ from copper, such as their thermal expansion coefficients (CTEs), surface energy, etc. These differences affect the formation and stability of the interface between copper and PI films, resulting in a short life for LED transparent screens. To enhance PI-copper interfacial adhesion, aminopropyl-terminated polydimethylsiloxane (PDMS) can be used to increase the adhesive ability. Two diamine monomers with a trifluoromethyl structure and a sulfone group structure were selected in this research. Bisphenol type A diether dianhydride is a dianhydride monomer. All three of the above monomers have non-coplanar structures and flexible structural units. The adhesion and optical properties can be improved between the interface of the synthesized PI films and copper foil. PI films containing PDMS 0, 1, 3, and 5 wt% were analyzed using UV spectroscopy. The transmittance of the PI-1/3%, PI-1/5%, PI-2/3%, and PI-2/5% films were all more than 80% at 450 nm. Meanwhile, the T and T heat loss and Tg temperatures decreased gradually with the increase in PDMS. The peel adhesion of PI-copper foil was measured using a 180° peel assay. The effect of PDMS addition on peel adhesion was analyzed. PIs-3% films had the greatest peeling intensities of 0.98 N/mm and 0.85 N/mm.
PubMed: 38891537
DOI: 10.3390/polym16111591 -
Polymers May 2024Only 0.1% of polyurethanes available on the market are from renewable sources. With increasing concern about climate change, the substitution of monomers derived from...
Only 0.1% of polyurethanes available on the market are from renewable sources. With increasing concern about climate change, the substitution of monomers derived from petrochemical sources and the application of eco-friendly synthesis processes is crucial for the development of biomaterials. Therefore, polyhydroxyurethanes have been utilized, as their synthesis route allows for the carbonation of vegetable oils with carbon dioxide and the substitution of isocyanates known for their high toxicity, carcinogenicity, and petrochemical origin. In this study, polyhydroxyurethanes were obtained from carbonated soybean oil in combination with two diamines, one that is aliphatic (1,4-butadiamine (putrescine)) and another that is cycloaliphatic (1,3-cyclohexanobis(methylamine)). Four polyhydroxyurethanes were obtained, showing stability in hydrolytic and oxidative media, thermal stability above 200 °C, tensile strength between 0.9 and 1.1 MPa, an elongation at break between 81 and 222%, a water absorption rate up 102%, and contact angles between 63.70 and 101.39. New formulations of bio-based NIPHUs can be developed with the inclusion of a cycloaliphatic diamine (CHM) for the improvement of mechanical properties, which represents a more sustainable process for obtaining NIPHUs with the physicochemical, mechanical, and thermal properties required for the preparation of wound dressings.
PubMed: 38891461
DOI: 10.3390/polym16111514 -
Cells Jun 2024Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator...
Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator chlormequat chloride (CCC) can contribute to the causality and exacerbation of reproductive disorders. However, the mechanism by which CCC may cause Leydig cell attenuation remains poorly understood. In this study, TM3 Leydig cells were used to investigate the inhibitory effect of CCC on cell growth and its possible mechanism. The results showed that CCC caused apoptosis, pyroptosis, ferroptosis and necroinflammation in TM3 cells. By comparing the effects of ferroptosis inhibitor Ferrostatin-1 (Fer-1) and pan-Caspase inhibitor Z-VAD-FMK (ZVF) on lipid peroxidation and Caspase-mediated regulated cell death (RCD), we found that Fer-1 was better at rescuing the growth of TM3 cells than ZVF. Although ZVF reduced mitochondrial ROS level and inhibited the activation of Caspase3 and Caspase1, it could not significantly ameliorate lipid peroxidation and the levels of IL-1β and HMGB1 like Fer-1. Therefore, ferroptosis might be a key non apoptotic RCD mode responsible for CCC-driven inflammation, leading to weakened viability and proliferation of TM3 cells. In addition, overexpression of ferritin light chain (FTL) promoted the resistance of TM3 cells to CCC-induced ferroptosis-mediated inflammation and to some extent improved the inhibition of viability and proliferation. Altogether, ferroptosis-initiated inflammation might play a key role in CCC-impaired TM3 cell growth.
Topics: Ferroptosis; Animals; Male; Mice; Leydig Cells; Inflammation; Cell Proliferation; Lipid Peroxidation; Reactive Oxygen Species; Cell Line; Apoptosis; Mitochondria; Amino Acid Chloromethyl Ketones; Cyclohexylamines; Phenylenediamines
PubMed: 38891111
DOI: 10.3390/cells13110979 -
BMC Oral Health Jun 2024One of the most prevalent health problems affecting children worldwide is untreated caries in primary teeth. Agents to arrest caries are used to manage untreated decay... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
One of the most prevalent health problems affecting children worldwide is untreated caries in primary teeth. Agents to arrest caries are used to manage untreated decay in children in disadvantaged communities. Nano Silver Fluoride (NSF) overcomes the staining problems of Silver Diamine Fluoride (SDF). This study compared the clinical cariostatic effect of NSF to 38% SDF for arresting caries lesions.
METHODS
The study included 360 children younger than 4 years, with at least one active lesion, ICDAS score ≥ 3, recruited from nurseries in a rural area in Alexandria, Egypt, in 2022. They were randomly assigned to receive a single application of NSF at baseline, or two applications of SDF at baseline and after 6 months. The arrest of active carious lesions was assessed after 6 and 12 months using ICDAS criteria, and parents' satisfaction with child appearance was also assessed. Chi-Square test was used to compare the groups and multi-level multiple logistic regression was used to assess the effect of the intervention on caries arrest at lesion level and binary logistic regression was used to assess the effect at patient level.
RESULTS
1853 active lesions were included in children whose mean (SD) age was 42.3 (8.2) months. The arrest rate was significantly higher in the NSF than the SDF group at lesion level (78.4% and 65.0% at 6 months and 71.3% and 56.3% at 12 months, p < 0.001). In regression analysis, NSF had significantly higher odds of caries arrest than SDF at lesion level (at 6 months, AOR = 2.57, 95% CI: 1.55, 4.26 and at 12 month, AOR = 3.27, 95% CI: 1.89, 5.67). Parents of children receiving NSF had significantly greater satisfaction with their children's dental appearance than those receiving SDF: (97.2% and 76.1%, respectively, p < 0.001).
CONCLUSION
NSF demonstrated greater effectiveness in arresting caries in preschool children without inducing black staining of teeth and with greater parental satisfaction than SDF. NSF can be an alternative to SDF in arresting caries especially in underprivileged communities.
TRIAL REGISTRATION
The trial was registered in the clinicaltrials.gov registry (#NCT05255913)-16/02/2022.
Topics: Humans; Dental Caries; Silver Compounds; Fluorides, Topical; Quaternary Ammonium Compounds; Child, Preschool; Female; Male; Cariostatic Agents; Fluorides; Infant; Treatment Outcome
PubMed: 38890627
DOI: 10.1186/s12903-024-04406-3 -
European Journal of Paediatric Dentistry Jun 2024Evaluate the effectiveness of biannual 38% SDF in arresting early childhood caries (ECC) compared to atraumatic restorative treatment (ART).
AIM
Evaluate the effectiveness of biannual 38% SDF in arresting early childhood caries (ECC) compared to atraumatic restorative treatment (ART).
METHODS
One hundred children (aged 2-5 years) with ECC were (2-5 years) divided equally and randomly into two groups. Test group: 38% SDF biannually; Control group: ART. The primary outcome was caries arrestarrest, which was assessed at the 3,6,9, and 12 months interval. Oral health- related quality of life (OHRQoL) was evaluated at base line and after 12 months using the Parental-Caregiver Perceptions Questionnaire (P-CPQ) and Family Impact Scale (FIS).
CONCLUSION
SDF was considerably more effective in arresting ECC after 12 months compared to ART. An overall significant improvement of OHRQoL was reported for both groups with SDF being faintly superior to ART.
PubMed: 38888598
DOI: 10.23804/ejpd.2024.2052 -
Primary Dental Journal Jun 2024Silver diamine fluoride (SDF) and atraumatic restorative treatment (ART) are treatment modalities that are minimally invasive and used for the prevention and control of... (Review)
Review
Silver diamine fluoride (SDF) and atraumatic restorative treatment (ART) are treatment modalities that are minimally invasive and used for the prevention and control of dental caries. The amalgamation of these two techniques has led to the development of silver modified atraumatic restorative treatment (SMART). In this approach the carious lesion is restored with glass-ionomer cement (GIC) after SDF application. SMART effectively arrests caries without removing additional tooth structure, making it a promising option for caries management in children who lack cooperative ability.This article reviews the literature on SMART, the evidence regarding its applications in dental practice, its advantages, drawbacks, the scope for research, and clinical use.
Topics: Humans; Dental Caries; Silver Compounds; Dental Atraumatic Restorative Treatment; Fluorides, Topical; Quaternary Ammonium Compounds; Glass Ionomer Cements; Cariostatic Agents; Child
PubMed: 38888074
DOI: 10.1177/20501684241249545 -
PeerJ 2024Keloid is a chronic proliferative fibrotic disease caused by abnormal fibroblasts proliferation and excessive extracellular matrix (ECM) production. Numerous fibrotic...
BACKGROUND
Keloid is a chronic proliferative fibrotic disease caused by abnormal fibroblasts proliferation and excessive extracellular matrix (ECM) production. Numerous fibrotic disorders are significantly influenced by ferroptosis, and targeting ferroptosis can effectively mitigate fibrosis development. This study aimed to investigate the role and mechanism of ferroptosis in keloid development.
METHODS
Keloid tissues from keloid patients and normal skin tissues from healthy controls were collected. Iron content, lipid peroxidation (LPO) level, and the mRNA and protein expression of ferroptosis-related genes including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined. Mitochondrial morphology was observed using transmission electron microscopy (TEM). Keloid fibroblasts (KFs) were isolated from keloid tissues, and treated with ferroptosis inhibitor ferrostatin-1 (fer-1) or ferroptosis activator erastin. Iron content, ferroptosis-related marker levels, LPO level, mitochondrial membrane potential, ATP content, and mitochondrial morphology in KFs were detected. Furthermore, the protein levels of α-smooth muscle actin (α-SMA), collagen I, and collagen III were measured to investigate whether ferroptosis affect fibrosis in KFs.
RESULTS
We found that iron content and LPO level were substantially elevated in keloid tissues and KFs. SLC7A11, GPX4, and Nrf2 were downregulated and TFRC was upregulated in keloid tissues and KFs. Mitochondria in keloid tissues and KFs exhibited ferroptosis-related pathology. Fer-1 treatment reduced iron content, restrained ferroptosis and mitochondrial dysfunction in KFs, Moreover, ferrostatin-1 restrained the protein expression of α-SMA, collagen I, and collagen III in KFs. Whereas erastin treatment showed the opposite results.
CONCLUSION
Ferroptosis exists in keloid. Ferrostatin-1 restrained ECM deposition and fibrosis in keloid through inhibiting ferroptosis, and erastin induced ECM deposition and fibrosis through intensifying ferroptosis.
Topics: Humans; Ferroptosis; Keloid; Fibroblasts; Cyclohexylamines; Fibrosis; Phenylenediamines; NF-E2-Related Factor 2; Phospholipid Hydroperoxide Glutathione Peroxidase; Male; Lipid Peroxidation; Female; Adult; Iron; Amino Acid Transport System y+; Receptors, Transferrin; Piperazines; Actins; Mitochondria; Membrane Potential, Mitochondrial
PubMed: 38887622
DOI: 10.7717/peerj.17551