Search Results (68)

Silver diamine fluoride/potassium iodide (SDF/KI) Riva Star (SDI) is a tooth desensitizing and anti-caries agent that may be indicated for arresting caries before restoring the tooth in selective caries approach. The aim was to determine the effect of SDF/KI pretreatment on the bonding of SDR Plus Bulk-Fill Flowable (Dentsply) with Clearfil SE Bond 2 (Kuraray) and G-Premio Bond (GC) in self-etch mode on sound dentin. A total of 240 dentin samples were prepared and assigned to 12 groups based on SDF/KI pretreatment (with or without), adhesive type, and testing time (1, 3, and 6 months). The shear bond strength (SBS) was measured using an UltraTester. SBS data were analyzed using three-way factorial model (Adhesive × Pretreatment × Time) and Wald (F) tests, with α = 0.05. Fracture modes were analyzed using χ² and Fisher’s exact test, with α = 0.05. Clearfil performed significantly better than G-Premio at all time points (p < 0.001). Riva Star pretreatment significantly reduced SBS for both adhesives at all time points (p < 0.001). SBS reduction was significantly higher for Clearfil (p < 0.001). The effect of storage was not significant (p = 0.388). Fracture mode distribution differed significantly between adhesives (p < 0.001). Pretreatment × fracture interaction was significant for Clearfil (p = 0.0052). Mixed fractures in G-premio were rare. Full article

Background/Objectives: The present study investigated the local analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone, or BHMC, in a mouse model of peripheral nociception. Methods: Local administration of BHMC (0.5–60 µg/paw) intra-plantarly in the hindpaws of mice exhibited significant inhibition in carrageenan-induced paw hyperalgesia. Intra-plantar pretreatment of naloxone (non-selective opioid receptor blocker), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2 (CTOP, selective µ-opioid receptor blocker), and nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not naltrindole hydrochloride (selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. The peripheral analgesic effect of BHMC was also reversed by intra-plantar pretreatment of methylene blue (soluble guanosyl cyclase blocker), but not N^G-nitro-L-arginine (L-NAME, nitric oxide synthase blocker). Involvement of the potassium channel in the local analgesic effect of BHMC was shown through the reversed analgesic effect by intra-plantar pretreatment of glibenclamide (ATP-sensitive potassium channel blocker), but not by charybdotoxin (large-conductance calcium-sensitive potassium channel blocker), apamin (small-conductance calcium-sensitive potassium ion channel blocker), or tetraethylammonium (voltage-sensitive potassium channel blocker). Results: Taken together, the present study demonstrated that the local administration of BHMC attenuated nociception, with possible mechanisms that may involve the desensitization of inflammatory mediators’ receptors, opioid receptor activation, and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium ion channel opening. Conclusions: The current findings may further support the exploration of BHMC as a new therapeutic agent for pain and inflammation, for the betterment of human health. Full article

Background/Objectives: Dentin hypersensitivity (DH) is associated with gingival recession and dentin exposure. Biomimetic hydroxyapatite (HAp) reduces DH by occluding dentinal tubules, with conventional toothpaste formulations showing benefits. High-density HAp mouthwashes may enhance bioavailability, but comparative evidence is scarce. This trial assessed the immediate desensitizing efficacy of a conventional HAp toothpaste and a high-density HAp mouthwash after professional oral hygiene. Methods: One hundred participants were randomized 1:1 to Biorepair^® (Coswell S.p.A., Funo, BO, Italy) Total Protection Toothpaste (Control) or Biorepair^® (Coswell S.p.A., Funo, BO, Italy) High-Density Mouthwash (Test). Assessments were performed at baseline (T0), post-debridement (T1), and after product use (T2). The primary endpoint was patient-level Schiff Air Index (SAI). Secondary endpoints included tooth-level SAI, Visual Analog Scale (VAS) scores, and gingival recession (GR). The trial was registered at ClinicalTrials.gov (NCT07057141) and followed CONSORT 2025 guidelines. Friedman and Dunn’s tests and regression models were applied. Results: Both groups showed significant reductions in hypersensitivity. Patient-level mean SAI decreased from 1.47 to 0.66 in the Control and from 1.48 to 0.45 in the Test group, while VAS declined from 3.66 to 1.57 (Control) and from 4.15 to 1.37 (Test). Post hoc analyses showed significant intragroup reductions between T0/T1 and T2 in both groups, with no significant differences between groups at any timepoint. GR remained stable across the study. Regression analyses identified follow-up time and GR as significant predictors, whereas treatment allocation was not, indicating that the acute advantage of the mouthwash at T2 did not persist once longitudinal trends were considered. Conclusions: Both HAp formulations effectively reduced dentin hypersensitivity 30 s after application. The high-density mouthwash exhibited slightly lower mean values at T2, although these differences were not statistically significant. Full article

Background: Doxorubicin (DOX) is a widely used chemotherapeutic agent, but its efficacy is often limited by cancer cell resistance. Although multiple DOX resistance mechanisms have been characterized, the global transcriptomic alterations underlying this phenomenon remain poorly understood. The aim of this work was to determine whether a common transcriptional response associated with DOX desensitization exists across tumor cells of different origins and to identify the core elements of this response. Methods: We performed an integrated bioinformatics analysis, including: analysis of independent transcriptomic datasets (comparing DOX-resistant neuroblastoma, breast, and cervical carcinoma cells to their DOX-sensitive counterparts), functional annotation of differentially expressed genes, reconstruction and topology analysis of gene networks, text mining, and survival analysis. The findings were validated through in vitro functional tests, RT-PCR, and analysis of the Cancer Therapeutics Response Portal and The Cancer Genome Atlas. Results: We showed that DOX resistance in cancer cells is associated with cytoskeletal reorganization, modulation of cell adhesion, cholesterol biosynthesis, and dysregulation of mTORC1, Wnt, and Gβγ signaling pathways. Network analysis identified a conserved regulome of 37 resistance-linked genes, with GJA1, SEH1L, TCF3, TUBA4A, and ZYX emerging as central hubs (mean degree: 8.7–19.7; mean fold change: 2.4–21.3). Experimental validation in DOX-resistant KB-8-5 cervical carcinoma cells and their sensitive counterparts (KB-3-1) confirmed enhanced cellular adhesion and reduced intracellular cholesterol levels associated with chemoresistance, supporting our in silico findings. A detailed follow-up analysis verified the upregulation of these hub genes in chemoresistant cells and their correlation with poor clinical outcomes across multiple cancer types. Conclusions: This integrative analysis identifies conserved transcriptomic signatures of DOX resistance and highlights hub genes GJA1, SEH1L, TCF3, TUBA4A, and ZYX with potential as predictive biomarkers and therapeutic targets. Targeting these pathways may help overcome chemoresistance and improve treatment outcomes in cancer patients. Full article

Gepirone, a selective 5-hydroxytryptamine (serotonin) 1A (5-HT_1A) receptor agonist, offers a promising strategy for treating mood and anxiety disorders. The therapeutic importance of 5-HT_1A modulation is well established, as these receptors regulate serotonergic neurotransmission both presynaptically, in the somatodendritic regions of raphe neurons, and postsynaptically, in structures including the hippocampus, neocortex, septum, amygdala, and hypothalamus. Gepirone exhibits a distinctive pharmacological profile, acting as a full agonist at presynaptic autoreceptors and a partial agonist at postsynaptic receptors, with high affinity for 5-HT_1A and much lower affinity for 5-HT_2A receptors. Its effects on serotonergic signaling are time-dependent. Acute administration suppresses serotonergic firing through autoreceptor activation, while chronic treatment induces autoreceptor desensitization, leading to enhanced 5-HT release in projection areas. This process is complemented by partial agonism at postsynaptic 5-HT_1A receptors, which further supports long-term neuromodulation. This article provides an integrated overview of gepirone’s mechanism of action, bridging receptor pharmacology, neurophysiological adaptations, and therapeutic implications. Particular emphasis is placed on the compound’s unique dual role in regulating serotonergic tone over time, a feature that differentiates it from other 5-HT_1A-targeting agents. By linking molecular mechanisms to clinical outcomes, we highlight gepirone’s potential advantages in efficacy, safety, and tolerability compared with conventional antidepressants. This comprehensive perspective underscores gepirone as a paradigmatic example of selective 5-HT_1A modulation and offers novel insights into the development of targeted treatments for depression and anxiety. Full article

Glyoxalase 1 (Glo1) functions as a catalyst that neutralizes methylglyoxal (MG), a highly reactive glycating agent predominantly produced during glycolysis—a metabolic pathway upregulated in cancer cells. MG primarily reacts with the amino groups of proteins (especially at arginine residues), leading to the formation of a major advanced glycation end product known as MG-derived hydroimidazolone 1 (MG-H1). We previously demonstrated in PC3 human prostate cancer (PCa) cells that the PTEN/PKM2/ERα axis promotes their aggressive phenotype by regulating the Glo1/MG-H1 pathway. In this study, after confirming our earlier findings, we investigated the downstream mechanisms of the PTEN/PKM2/ERα/Glo1/MG-H1 axis in controlling PC3 cell growth, focusing on the role of RAGE, a high-affinity receptor for MG-H1; hydrogen peroxide (H₂O₂); and Krev interaction trapped 1 (KRIT1), an emerging tumor suppressor. Using genetic approaches and specific inhibitors/scavengers, we demonstrated that the PTEN/PKM2/ERα/Glo1/MG-H1 axis promotes PC3 cell growth—measured by proliferation and etoposide-induced apoptosis resistance—through a mechanism involving MG-H1/RAGE pathway desensitization that leads to H₂O₂-mediated KRIT1 downregulation. These findings support and expand the role of PTEN signaling in PCa progression and shed light on novel mechanistic pathways driven by MG-dependent glycative stress, involving KRIT1, in this still incurable stage of the disease. Full article

Although caries is declining in industrialized countries, early childhood caries and molar–incisor hypomineralization (MIH) remain clinically relevant. To meet the demand for effective and well-tolerated preventive strategies, hydroxyapatite (HAp) has gained attention as a biocompatible, fluoride-free agent. A structured narrative review was conducted to evaluate recent clinical evidence on the use of HAp. A PubMed search identified clinical trials from the past five years that investigated HAp-based products. Studies were included if they reported clinical outcomes related to remineralization, caries prevention, or desensitization. Fifteen clinical studies met the inclusion criteria. HAp seems to be a safe and effective alternative to flouride, especially for children or individuals at risk of overexposure. While both agents show similar efficacy in caries prevention, HAp may offer additional advantages in managing hypersensitivity and MIH. Compared to other remineralizing agents, such as calcium sodium phosphosilicate, HAp demonstrated comparable efficacy. Combination therapies show the most promising results. Future research should explore synergies of active ingredients and include standardized long-term studies to substantiate the clinical relevance of HAp. Full article

Automotive intelligent agents are increasingly collecting facial data for applications such as driver behavior monitoring and identity verification. These excessive collections of facial data bring serious risks of sensitive information leakage to autonomous driving. Facial information has been explicitly required to be anonymized, but the availability of most desensitized facial data is poor, which will greatly affect its application in autonomous driving. This paper proposes an automotive sensitive information anonymization method with high-quality generated facial images by considering the data availability under privacy protection. By comparing K-Same and Generative Adversarial Networks (GANs), this paper proposes a hierarchical self-attention mechanism in StyleGAN3 to enhance the feature perception of face images. The synchronous regularization of sample data is applied to optimize the loss function of the discriminator of StyleGAN3, thereby improving the convergence stability of the model. The experimental results demonstrate that the proposed facial desensitization model reduces the Frechet inception distance (FID) and structural similarity index measure (SSIM) by 95.8% and 24.3%, respectively. The image quality and privacy desensitization of the facial data generated by the StyleGAN3 model have been fully verified in this work. This research provides an efficient and robust facial privacy protection solution for autonomous driving, which is conducive to promoting the security guarantee of automotive data. Full article

Background/Objectives: Toothbrushing is a recommended daily practice that helps sustain oral health. However, if performed improperly, it can lead to loss of tooth structure and injury to soft tissues. We explored this topic with an extensive literature search. Methods: A literature search was performed across textbooks and journals for original research and review articles in Scopus, PubMed, PubMed Central, and Cochrane databases, published between 1967 and 2024. Results: The search result yielded 118 articles that were suitable to include in this review. Toothpaste abrasivity plays a major role in combination with toothbrush forces. Therefore, maintaining forces between 2 and 3 N may be gentler on the tissue. Electric toothbrushes are safer. Toothpastes with low RDA values are also less abrasive. Active ingredients in whitening and desensitizing toothpaste can induce tooth wear. Remineralizing agents have the potential to manage the associated lesions. Conclusions: Cervical abrasions and gingival recession occur frequently due to oral hygiene measures. Standards in oral hygiene aid to match patient needs can prevent hard and soft tissue loss. Full article

Background: A large number of patients suffer from neuropathic pain, and systemic therapy often remains ineffective while inducing severe side effects. Topical therapy with the TRPV1-agonist capsaicin is an established alternative, and the identification of co-therapeutics that modulate TRPV1 may be a promising approach to reduce the dose of capsaicin while maintaining efficacy. Here, we aimed to determine if the antidepressant amitriptyline displays properties rendering it a potential co-therapeutic agent. Methods: We performed patch clamp and calcium imaging experiments on HEK293T cells expressing human (h) TRPV1 as well as on dorsal root ganglion (DRG) neurons from adult mice. Results: Amitriptyline induced an increase in intracellular calcium in both HEK293T and mouse DRG neurons expressing TRPV1. Patch clamp experiments revealed a concentration-dependent activation of hTRPV1 by amitriptyline that was also evident in cell-free inside-out patches. When hTRPV1 was fully activated by capsaicin, amitriptyline induced concentration-dependent and partly reversible current inhibition. In contrast, amitriptyline potentiated small responses to capsaicin, heat and protons. We also found that amitriptyline desensitized hTRPV1 to capsaicin. This effect was reduced by the intracellular application of the strong calcium chelator BAPTA. Furthermore, the non-desensitizing mutant hTRPV1-Y672K displayed a reduced amitriptyline-induced desensitization. Conclusions: Our data showed that amitriptyline can activate, sensitize, desensitize and even inhibit TRPV1. Together with its property as a strong local anesthetic, our data suggest that amitriptyline may be a promising adjunct to topical capsaicin. Full article

The cancer chemotherapy regimen of a taxane and platinum combination was developed more than forty years ago, yet remains the cornerstone of treatment for several major cancer types today. Although many new agents targeting cancer genes and pathways have been developed and evaluated, none have been sufficient to replace the long-established taxane/platinum combination. This leads us to ponder why, after four decades of colossal efforts, multiple discoveries, and tremendous advances in understanding gene mutations and biology, the development of conceptually superior targeted therapies has not yet achieved overwhelming success in replacing cytotoxic chemotherapy. The concept of targeted therapy is based on the idea that blocking the altered pathway(s) crucial for cancer development (and maintenance), the disturbance in cellular signaling, metabolism, and functions will make the targeted cancer cells unfit and trigger programmed cell death in cancer cells, but without the significant side effects that limit chemotherapy. We propose that the lack of anticipated triumphs of targeted therapy stems from the desensitization of programmed cell death pathways during neoplastic transformation and malignant progression of cancer cells. This renders the targeting drugs largely ineffective at killing cancer cells and mostly insufficient in clinical implements. Recent advances in understanding suggest that, in contrast to targeted therapies, taxanes and platinum agents kill cancer cells by physical rupturing nuclear membranes rather than triggering apoptosis, making their effect independent of the intrinsic cellular programmed cell death mechanism. This new recognition of the non-programmed cell death mechanism in the success of chemotherapeutic agents, such as taxanes and platinum, may inspire oncologists and cancer researchers to focus their efforts more productively on developing effective non-programmed cell death cancer therapies to replace or significantly improve the application of the current standard taxane/platinum regimens. Full article

Peanut allergy, a significant public health issue, poses challenges due to its potential for life-threatening anaphylaxis and profound impact on quality of life. Traditional management approaches, including allergen avoidance and epinephrine administration, are effective in mitigating acute symptoms but do not address the underlying allergy or long-term disease burden. Recent advances in immunotherapy and biologics, as well as innovative technologies such as gene editing and microbiome modulation, have introduced promising pathways for desensitization and sustained unresponsiveness. This review provides a comprehensive exploration of emerging therapies for peanut allergy, including oral, sublingual, and epicutaneous immunotherapy, biologic agents, gene-editing techniques, and novel drug therapies. We discuss their mechanisms, clinical efficacy, and associated challenges, emphasizing the potential for these innovations to revolutionize peanut allergy treatment. Despite significant progress, barriers such as adverse reactions, cost, and limited access remain. Addressing these challenges through further research and standardization could transform the future of peanut allergy management. Full article

Due to its central role in pain, inflammation, and related disorders, the Transient Receptor Potential (TPR) Vanilloid Type-1 (TRPV1) ion channel represents an attractive target for the development of novel antinociceptive and anti-inflammatory agents. Capsaicin, the natural component of chili peppers, is one of the most investigated agonists of this receptor. Several modifications of its structure have been attempted, aiming at finding TRPV1 agonists with improved characteristics, but, to date, no capsaicin-derived agents have reached the market. Based on our previous knowledge of the design and synthesis of TRPV1 agonists, in this paper we propose two small series of indole-2-carboxamides as novel and selective agonists for this ion channel. The newly developed compounds have been structurally characterized and tested in vitro for their ability to modulate TRPV1, in terms of efficacy, potency (EC₅₀), and desensitization (IC₅₀) properties. For the most promising derivatives, selectivity over the TRP ankyrin-1 (TRPA1) channel has been reported. From our study, compound 6g arose as a promising candidate for further evaluation, also in correlation with its in silico-predicted drug-like properties. Full article

In severe asthma, symptoms are unstable despite intensive treatment based on high doses of inhaled corticosteroids and on-demand use of oral corticosteroids. Although, recently, various biological agents related to Th2 cytokines have been added to intensive controller medications for severe asthma, a significant progress has not been observed in the management for symptoms (dyspnea, wheezing and cough). Medical treatment focused on Type 2 inflammation is probably insufficient to maintain good long-term management for severe asthma. Airway eosinophilia and decreased reversibility in forced expiratory volume in 1 second (FEV₁) are listed as major predictors for exacerbation-prone asthma. However, it is generally considered that asthma is complex and heterogeneous. It is necessary to establish precision medicine using treatable traits based on a multidimensional approach related to asthma. Since phospholipids generate lysophospholipids and arachidonic acid by phospholipases, lysophospholipids can be associated with the pathogenesis of this disease via action on smooth muscle, endothelium, and epithelium in the airways. Lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), and sphingosine 1-phosphate (S1P) are increased in bronchoalveolar fluid after allergen challenge. LPA, LPC, and S1P recruit eosinophils to the lungs and cause β₂-adrenergic desensitization. LAP and S1P cause contraction and hyperresponsiveness in airway smooth muscle. Moreover, lysophosphatidylserine and S1P are associated with the allergic reaction related to IgE/FcεRI in mast cells. Lysophospholipid action is probably comprised of corticosteroid resistance and is independent of Type 2 inflammation, and may be corelated with oxidative stress. Lysophospholipids may be a novel molecular target in advancing the management and treatment of asthma. This review discusses the clinical relevance of lysophospholipids in asthma. Full article

Background: Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in children. A hallmark of the disease is the rapid remission of proteinuria following a high dose of steroids. Recurrent disease or steroid dependence are common, leading to a high steroid burden and the introduction of steroid sparing therapy. Anti-CD20 antibodies have been increasingly used with excellent results in complicated INS. Nevertheless, their use can be limited by the occurrence of infusion-related reactions (IRRs). Methods: This report discusses further treatment options for children who are intolerant to RTX and presents the first report of a successful switch to obinutuzumab (OBI) for a child with difficult-to-treat steroid-dependent nephrotic syndrome (SDNS) and RTX intolerance who was unresponsive to a desensitization protocol. Results: A 12-year-old boy with SDNS since the age of 2, was treated with steroids, cyclophosphamide and cyclosporine A (CsA). Because of the prolonged use of calcineurin inhibitors, a course of rituximab (RTX) was planned. Unfortunately, during first infusion, the boy presented with IRR. A desensitization protocol following the first unsuccessful infusion also failed. Facing the risks of long-term cyclosporine therapy, a decision was made to switch to another type of anti-CD20 antibody. Obinutuzumab infusion with a modified premedication scheme was uneventful. Conclusions: Switching therapy to obinutuzumab may be considered an option in nephrotic children who are intolerant to RTX when alternative therapies have been exhausted. The addition of montelukast to premedication and employment of desensitization protocols may decrease the risk of infusion-related reactions to anti-CD20 agents. Full article