Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.

BACKGROUND: The desirable properties of silver diamine fluoride (SDF) make it an effective agent for managing dental caries and tooth hypersensitivity. There are several clinical instances that SDF application might precede the placement of direct tooth-colored restorations. On the other hand, SDF stains demineralized/carious dental tissues black, which might affect the esthetic outcomes of such restorations. Color is a key parameter of esthetics in dentistry. Therefore, this study aims to systematically review dental literature on color/color change of tooth-colored restorations placed following the application of SDF on dentine.
METHODS: Comprehensive search of PubMed, Embase, Scopus and ISI Web of Science databases (until August 2023) as well as reference lists of retrieved studies was performed. In vitro studies reported color or color change of tooth-colored restorative materials applied on SDF-treated dentine were included. Methodological quality assessment was performed using RoBDEMAT tool. Pooled weighted mean difference (WMD) and 95% confidence interval (95% CI) was calculated.
RESULTS: Eleven studies/reports with a total of 394 tooth-colored restorations placed following a) no SDF (control) or b) SDF with/without potassium iodide (KI)/glutathione dentine pre-treatments were included. Color change was quantified using ∆E formulas in most reports. The pooled findings for the comparison of resin-based composite (RBC) restorations with and without prior 38% SDF + KI application revealed no statistically significant differences in ∆E values at short- and long-term evaluations (~ 14 days: WMD: -0.56, 95% CI: -2.09 to 0.96; I2: 89.6%, and ~ 60 days: WMD: 0.11; 95% CI: -1.51 to 1.72; I2: 76.9%). No studies provided sufficient information for all the items in the risk of bias tool (moderate to low quality).
CONCLUSIONS: The limited evidence suggested comparable color changes of RBC restorations with and without 38% SDF + KI pre-treatment up to 60 days. The included studies lacked uniformity in methodology and reported outcomes. Further studies are imperative to draw more definite conclusions.
BACKGROUND: The protocol of this systematic review was registered in PROSPERO database under number CRD42023485083.

Lipid peroxidation plays an important role in various pathologies and aging, at least partially mediated by ferroptosis. The role of mitochondrial lipid peroxidation during ferroptosis remains poorly understood. We show that supplementation of exogenous iron in the form of ferric ammonium citrate at submillimolar doses induces production of reactive oxygen species (ROS) and lipid peroxidation in mitochondria that precede ferroptosis in H9c2 cardiomyocytes. The mitochondria-targeted antioxidant SkQ1 and the redox mediator methylene blue, which inhibits the production of ROS in complex I of the mitochondrial electron transport chain, prevent both mitochondrial lipid peroxidation and ferroptosis. SkQ1 and methylene blue also prevented accumulation of lipofuscin observed after 24 h incubation of cardiomyocytes with ferric ammonium citrate. Using isolated cardiac mitochondria as an in vitro ferroptosis model, it was shown that rotenone (complex I inhibitor) in the presence of ferrous iron stimulates lipid peroxidation and lipofuscin accumulation. Our data indicate that ROS generated in complex I stimulate mitochondrial lipid peroxidation, lipofuscin accumulation, and ferroptosis induced by exogenous iron.

The nuclear pore complex (NPC) is a proteinaceous nanopore that solely and selectively regulates the molecular transport between the cytoplasm and nucleus of a eukaryotic cell. The ∼50 nm-diameter pore of the NPC perforates the double-membrane nuclear envelope to mediate both passive and facilitated molecular transport, thereby playing paramount biological and biomedical roles. Herein, we visualize single NPCs by scanning electrochemical microscopy (SECM). The high spatial resolution is accomplished by employing ∼25 nm-diameter ion-selective nanopipets to monitor the passive transport of tetrabutylammonium at individual NPCs. SECM images are quantitatively analyzed by employing the finite element method to confirm that this work represents the highest-resolution nanoscale SECM imaging of biological samples. Significantly, we apply the powerful imaging technique to address the long-debated origin of the central plug of the NPC. Nanoscale SECM imaging demonstrates that unplugged NPCs are more permeable to the small probe ion than are plugged NPCs. This result supports the hypothesis that the central plug is not an intrinsic transporter, but is an impermeable macromolecule, e.g., a ribonucleoprotein, trapped in the nanopore. Moreover, this result also supports the transport mechanism where the NPC is divided into the central pathway for RNA export and the peripheral pathway for protein import to efficiently mediate the bidirectional traffic.

Newly synthesized gemini quaternary ammonium salts (QAS) with different counterions (bromide, hydrogen chloride, methylcarbonate, acetate, lactate), chain lengths (C12, C14, C16) and methylene linker (3xCH2) were tested. Dihydrochlorides and dibromides with 12 carbon atoms in hydrophobic chains were characterized by the highest biological activity against planktonic forms of yeast and yeast-like fungi. The tested gemini surfactants also inhibited the production of filaments by C. albicans. Moreover, they reduced the adhesion of C. albicans cells to the surfaces of stainless steel, silicone and glass, and slightly to polystyrene. In particular, the gemini compounds with 16-carbon alkyl chains were most effective against biofilms. It was also found that the tested surfactants were not cytotoxic to yeast cells. Moreover, dimethylcarbonate (2xC12MeCO3G3) did not cause hemolysis of sheep erythrocytes. Dihydrochlorides, dilactate and diacetate showed no mutagenic potential.

Esterquats constitute a unique group of quaternary ammonium salts (QASs) that contain an ester bond in the structure of the cation. Despite the numerous advantages of this class of compounds, only two mini-reviews discuss the subject of esterquats: the first one (2007) briefly summarizes their types, synthesis, and structural elements required for a beneficial environmental profile and only briefly covers their applications whereas the second one only reviews the stability of selected betaine-type esterquats in aqueous solutions. The rationale for writing this review is to critically reevaluate the relevant literature and provide others with a \"state-of-the-art\" snapshot of choline-type esterquats and betaine-type esterquats. Hence, the first part of this survey thoroughly summarizes the most important scientific reports demonstrating effective synthesis routes leading to the formation of both types of esterquats. In the second section, the susceptibility of esterquats to hydrolysis is explained, and the influence of various factors, such as the pH, the degree of salinity, or the temperature of the solution, was subjected to thorough analysis that includes quantitative components. The next two sections refer to various aspects associated with the ecotoxicity of esterquats. Consequently, their biodegradation and toxic effects on microorganisms are extensively analyzed as crucial factors that can affect their commercialization. Then, the reported applications of esterquats are briefly discussed, including the functionalization of macromolecules, such as cotton fabric as well as their successful utilization on a commercial scale. The last section demonstrates the most essential conclusions and reported drawbacks that allow us to elucidate future recommendations regarding the development of these promising chemicals.

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).
CONCLUSIONS: 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.
BACKGROUND: The trial was registered in the clinicaltrials.gov registry (#NCT05255913)-16/02/2022.

Adjuvants are effective tools to enhance vaccine efficacy and control the type of immune responses such as antibody and T helper 1 (Th1)- or Th2-type responses. Several studies suggest that interferon (IFN)-γ-producing Th1 cells play a significant role against infections caused by intracellular bacteria and viruses; however, only a few adjuvants can induce a strong Th1-type immune response. Recently, several studies have shown that lipid nanoparticles (LNPs) can be used as vaccine adjuvants and that each LNP has a different adjuvant activity. In this study, we screened LNPs to develop an adjuvant that can induce Th1 cells and antibodies using a conventional influenza split vaccine (SV) as an antigen in mice. We observed that LNP with 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) as a component lipid (DOTMA-LNP) elicited robust SV-specific IgG1 and IgG2 responses compared with SV alone in mice and was as efficient as SV adjuvanted with other adjuvants in mice. Furthermore, DOTMA-LNPs induced robust IFN-γ-producing Th1 cells without inflammatory responses compared to those of other adjuvants, which conferred strong cross-protection in mice. We also demonstrated the high versatility of DOTMA-LNP as a Th1 cell-inducing vaccine adjuvant using vaccine antigens derived from severe acute respiratory syndrome coronavirus 2 and Streptococcus pneumoniae. Our findings suggest the potential of DOTMA-LNP as a safe and effective Th1 cell-inducing adjuvant and show that LNP formulations are potentially potent adjuvants to enhance the effectiveness of other subunit vaccines.

BACKGROUND: The black staining effect of silver-containing solutions for use to arrest caries can have a negative aesthetic impact on children and parents. This study aims to assess the staining effects of Silver Diamine Fluoride/Potassium Iodide (SDF/KI), SDF and Nanosilver Fluoride (NSF).
METHODS: Forty-four extracted carious primary molars were collected and randomly divided into four groups (n = 11). The carious tissue in all teeth was removed using a chemo-mechanical caries removal agent with an excavator. After caries removal in all groups, SDF, SDF/KI, and NSF were applied to the different groups, while no solution was applied to the control group. Subsequently, the teeth in all groups were restored with compomer. Color values L*, a* and b* were measured using a spectrophotometer at three time points: immediately after compomer restoration (T0), one week later (T1), and four week later (T2). Changes in brightness (ΔL) and color (ΔE) over time were calculated and comparisons among groups were made.
RESULTS: The SDF solution induced statistically significant black staining (p = 0.013) and a decrease in L* value (p < 0.001) on the compomer material compared to the other groups over time.
CONCLUSIONS: It was observed that SDF/KI has the potential to reduce the black staining effect of SDF, though not entirely. Novel experimental solutions like NSF may offer an alternative to counteract the staining effect of SDF.

BACKGROUND: Using Silver Diamine Fluoride (SDF) may be an effective public health approach for managing dental caries in children. Parental acceptance of SDF has rarely been investigated in low-income and middle-income countries (LMICs). The aim of this study was to evaluate parental acceptance of SDF to manage dental caries in children aged 2-12 in Iran and Tajikistan.
METHODS: This cross-sectional study was conducted in the Kurdistan province of Iran and Khatlon region of Tajikistan, 2022-2023. Parents watched a video about SDF and its weaknesses and strengths as compared to conventional approaches before completing the questionnaire. We also reported Prevalence Ratios with 95% confidence intervals for the relationship between parental acceptance and associated demographic factors as well as dental attitude and experience.
RESULTS: Participants were 245 and 160 parents in Iran and Tajikistan, respectively. In both countries, a majority (Iran: 61.6%, Tajikistan: 77.9%) accepted SDF over conventional treatments for all primary teeth. The majority also accepted SDF only for posterior permanent teeth (Iran: 73.5%, Tajikistan: 78.7%). Black discoloration was the main reason for rejecting SDF. Overall, demographic factors and dental experience and attitude were not significantly associated with SDF acceptance.
CONCLUSIONS: SDF was widely accepted by Iranian and Tajik parents. Establishing parental acceptance of SDF is an important step toward its application in LMICs where inexpensive solutions are needed.