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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 -
Cell Jun 2024The growth of antimicrobial resistance (AMR) highlights an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although...
The growth of antimicrobial resistance (AMR) highlights an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe infections profoundly alter host metabolism, prior studies have largely ignored microbial metabolism in this context. Here, we describe an iterative, comparative metabolomics pipeline to uncover microbial metabolic features in the complex setting of a host and apply it to investigate gram-negative bloodstream infection (BSI) in patients. We find elevated levels of bacterially derived acetylated polyamines during BSI and discover the enzyme responsible for their production (SpeG). Blocking SpeG activity reduces bacterial proliferation and slows pathogenesis. Reduction of SpeG activity also enhances bacterial membrane permeability and increases intracellular antibiotic accumulation, allowing us to overcome AMR in culture and in vivo. This study highlights how tools to study pathogen metabolism in the natural context of infection can reveal and prioritize therapeutic strategies for addressing challenging infections.
PubMed: 38885650
DOI: 10.1016/j.cell.2024.05.035 -
Macromolecular Rapid Communications Jun 2024Stimuli-responsive block copolymer nanoparticles (NPs) have received close attention in recent years owing to their tremendous application potential in smart materials....
Stimuli-responsive block copolymer nanoparticles (NPs) have received close attention in recent years owing to their tremendous application potential in smart materials. Azobenzene-containing NPs are widely studied due to the advantages of light as a stimulus and fast reversible trans-cis isomerization of azobenzene chromophores. However, the inefficient preparation process and difficult reversible transformation of morphologies limit their development. Herein it is demonstrated that the light-triggered reversible swelling behavior of wormlike NPs with high azobenzene content could be realized via confined deformation. These worms are prepared in large quantities via polymerization-induced self-assembly based on the copolymerization of 11-(4-(4-butylphenylazo)phenoxy)undecyl methacrylate (MAAz) and N-(methacryloxy)succinimide (NMAS) monomers. Upon UV/visible light irradiation, the reversible deformation of worms is achieved when the feed molar ratio of NMAS/MAAz is relatively high or via crosslinking using diamines, which leads to the reduction of the photoisomerization efficiency. The diameter variation of the worms is influenced by the amount and types of crosslinkers. Moreover, the scalability of this strategy is further proved by the fabrication of photo- and reductant-responsive crosslinked worms. It is expected that this study not only provides a new route to affording reversible photoresponsive NPs but also offers a unique insight into the reversible photodeformation mechanism of azobenzene-containing NPs.
PubMed: 38885423
DOI: 10.1002/marc.202400372 -
MedRxiv : the Preprint Server For... Jun 2024Dental caries is the world's most prevalent noncommunicable disease, disproportionately affecting children from low-income rural areas. This study assessed the...
BACKGROUND
Dental caries is the world's most prevalent noncommunicable disease, disproportionately affecting children from low-income rural areas. This study assessed the effectiveness of using silver diamine fluoride (SDF) for school-based caries prevention.
METHODS
The CariedAway 3.0 study was a cluster-randomized pragmatic non-inferiority trial comparing SDF to sealants and atraumatic restorations (ART) for the prevention and control of dental caries. All participants also received fluoride varnish. Analysis consisted of multilevel mixed-effects logistic and negative binomial regression for the prevalence and incidence of dental caries, respectively, and a non-inferiority margin of 10% for the difference between groups was used. Dental caries was defined as an ICDAS score of four or greater.
RESULTS
A total of 3345 children were enrolled in the trial, however there was a large proportion of children who were noncompliant and received external dental care. In adjusted analyses of compliant participants (n=1083, consisting of 543 in the SDF group and 540 in the sealant and ART group), there was no difference in the weighted risk difference between treatment groups (B=0.003, 95% CI = -0.0001, 0.0008). The odds of caries was elevated in the SDF group in longitudinal analyses (OR = 1.35, 95% CI = 0.86, 2.11) but was not significant and was below the non-inferiority margin. There were no significant differences between groups for caries incidence in adjusted models (IRR = 1.19, 95% CI = 0.81, 1.74). Results for intent to treat analyses were similar to that of per-protocol.
DISCUSSION
In this school-based clinical trial, the prevalence of dental caries in children treated with SDF and fluoride varnish was non-inferior compared to those treated with sealants, ART, and fluoride varnish, although the overall risk was slightly higher. Unfortunately, a high rate of dropout and participant noncompliance was observed, likely due to the impacts of COVID-19 on study procedures. As a result, observed effects may be unreliable beyond the short-term.
TRIAL REGISTRATION
NCT03448107.
PubMed: 38883737
DOI: 10.1101/2024.06.05.24308499 -
ACS Omega Jun 2024Oligo(azomethine)s bearing phosphate and silane moieties were the subject of an investigation within this study. The initial stage involved the synthesis of two Schiff...
Oligo(azomethine)s bearing phosphate and silane moieties were the subject of an investigation within this study. The initial stage involved the synthesis of two Schiff base monomers, denoted as SCH-1 and SCH-2 (SCHs), each possessing a pair of hydroxyl functional groups. This was achieved through a loss of water between the aldehyde and diamine precursors. Subsequently, the Schiff base entities were subjected to oligomerization through HCl-mediated elimination due to the interaction between the hydroxyl groups of the Schiff bases and the chlorine moieties of dichlorodiethylsilane (Si) or phenyl dichlorophosphate (P). This procedure yielded distinct P-oligo(azomethine) (P1-P, P2-P) and Si-oligo(azomethine) (P1-Si and P2-Si) structures corresponding to each precursor. The molecular structures of the synthesized Schiff base monomers and oligo(azomethine)s were elucidated employing Fourier transform infrared, H NMR, and C NMR techniques. Thermal properties of the resulting products were assessed by utilizing thermogravimetric analysis (TG-DTG/DTA and DSC) techniques. Scanning electron microscopy (SEM) was employed to acquire high-resolution images and detailed surface information on the samples. Additionally, X-ray diffraction was employed to analyze the phase properties of the solid samples. Furthermore, the optical band gap ( ) values of the resulting P-oligo(azomethine)s and Si-oligo(azomethine)s were determined utilizing UV-vis spectrophotometer. The relatively low band gap values exhibited by the synthesized oligo(azomethine)s were indicative of their potential suitability as semiconductive materials in the realm of electronic and optoelectronic device fabrication. Photoluminescence (PL) measurements disclosed a green emission profile upon excitation by blue light. The oligo(azomethine)s incorporating methoxy groups demonstrated a red shift in comparison to their counterparts with methyl groups. Remarkably, no discernible fluctuations in fluorescence were observed over a 3600 s interval under consistent conditions. This observation underscored the inherent stability of the PL emission across the spectral range of exciting light. Thermal analyses unveiled high thermal stability of the synthesized oligo(azomethine)s, sustaining their structural integrity up to 220 °C. The char % of P-oligo(azomethine)s and Si-oligo(azomethine)s were observed to fall within the range of 29.45-55.47% at 1000 °C. SEM images revealed the absence of pores on the surface of P2-Si, which exhibited the highest limiting oxygen index and thermal heat release index ( ) values.
PubMed: 38882123
DOI: 10.1021/acsomega.4c01403 -
ACS Omega Jun 2024The synthesis of metal macrocycle complexes holds paramount importance in coordination and supramolecular chemistry. Toward this end, we report a new, mild, and...
The synthesis of metal macrocycle complexes holds paramount importance in coordination and supramolecular chemistry. Toward this end, we report a new, mild, and efficient protocol for the synthesis of cyclometalated macrocycle Ir(III) complexes: [Ir()](PF) (), [Ir()](PF) (), and [Ir()](PF) (), where presents 10,17-dioxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclooctadecaphane, is 10,13,16,19,22,25-hexaoxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclohexacosaphane, and is 4-methyl-10,13,16,19,22,25-hexaoxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclohexacosaphane. This synthesis involves the preassembly of two symmetric 2-phenylquinoline arms into C-shape complexes, followed by cyclization with diamine via in situ interligand C-N cross-coupling, employing a metal ion as a template. Moreover, the synthetic yield of these cyclometalated Ir(III) complexes, tethered by an 18-crown-6 ether-like chain, is significantly enhanced in the presence of K ion as a template. The resultant cyclometalated macrocycle Ir(III) complexes exhibit high stability, efficient singlet oxygen generation, and superior catalytic activity for the aerobic selective oxidation of sulfides into sulfoxides under visible light irradiation in aqueous media at room temperature. The photocatalyst demonstrates recyclability and can be reused at least 10 times without a significant loss of catalytic activity. These results unveil a new and complementary approach to the design and in situ synthesis of cyclometalated macrocycle Ir(III) complexes via a mild interligand-coupling strategy.
PubMed: 38882114
DOI: 10.1021/acsomega.4c01111