Search Results (97,517)

The red imported fire ant (Solenopsis invicta) is a dangerous invasive insect. These ants rely on releasing an alarm pheromone, mainly composed of 2-ethyl-3,6-dimethylptrazine (EDMP), to warn nestmates of danger and trigger group defense or escape behaviors. This study found two NPC2 proteins in the ant antennae: SinvNPC2a and SinvNPC2b. SinvNPC2a was highly expressed in the antennae; phylogenetic analysis also suggests that SinvNPC2 likely possesses conserved olfactory recognition functions. By knocking down the SinvNPC2a gene, we found that the electrophysiological response of ant antennae to EDMP became weaker. More importantly, ants lacking SinvNPC2a showed significantly reduced movement range and speed when exposed to EDMP, compared to normal ants not treated with RNAi. These ants did not spread out quickly. Furthermore, tests showed that the purified SinvNPC2a protein could directly bind to EDMP molecules. Computer modeling also showed that they fit together tightly. These findings provide direct evidence that the SinvNPC2a protein plays a key role in helping fire ants detect the EDMP alarm pheromone. It enables the ants to sense this chemical signal, allowing ant colonies to respond quickly. Understanding this mechanism improves our knowledge of how insects smell things. It also suggests a potential molecular target for developing new methods to control fire ants, such as using RNAi to block its function. Full article

Impedance-based cellular assays allow determination of biological functions of cell populations in real-time by measuring electrical impedance. As compared to end-point assays, such as trans-epithelial electrical resistance assays, for example, they enable fast, non-invasive, and easy detection of cell kinetics—their growth, attachment, and interaction can be monitored over time. In our experiment, Caco-2 cells were cultured on E-plates 16. Next, fully differentiated cells were treated with either TNF-α or 3,4-dihydroxy-L-phenylalanine (L-DOPA). We aimed to verify the possibility of real-time testing of the viability, monolayer formation, and integrity (i.e., the presence of a functional and polarized monolayer) of Caco-2 cells by the xCELLigence real-time cell analyzer (RTCA) S16 system (Agilent Technologies). Full article

Background: Despite recent advances in the management of metastatic renal cell carcinoma (mRCC), real-world outcomes remain heterogeneous, and early treatment failure is common. Predictive biomarkers for time to treatment failure (TTF) outside clinical trials are poorly characterized. Objective: To identify clinical and laboratory predictors associated with early treatment failure in a real-world cohort of mRCC patients treated with immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), or combination regimens. Methods: We conducted a retrospective, single-center analysis of patients with metastatic non-urothelial RCC treated between 2018 and 2023. Cox proportional hazards regression was used to evaluate the association between baseline biological parameters and TTF for each treatment regimen. Results: Among 137 patients receiving first-line therapy, 50 received Ipilimumab + Nivolumab, 49 Sunitinib, and 17 Avelumab + Axitinib. For Ipilimumab + Nivolumab, elevated AST was significantly associated with shorter TTF. For Avelumab + Axitinib, shorter TTF was associated with lymph node metastases, low lymphocyte count, low creatinine, low BMI, and low hemoglobin. For Cabozantinib in subsequent lines, a higher platelet count, ALT, and presence of liver metastases were associated with shorter TTF. No statistically significant predictors were found for Nivolumab used in the second-line setting. Conclusions: Routine, accessible biomarkers such as AST, hemoglobin, lymphocyte count, and creatinine may serve as predictors of treatment failure in specific therapeutic contexts. These findings support risk-adapted strategies and individualized monitoring in real-world clinical practice, though further validation in larger cohorts is warranted. Full article

Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy. Full article

Introduction: Radiomics is the extraction of non-invasive and reproducible quantitative imaging features, which may yield mineable information for clinical practice implementation. Quantification of lung function through radiomics could play a role in the management of patients with pulmonary lesions. The aim of this study is to test the capability of radiomic features to predict pulmonary function parameters, focusing on the diffusing capacity of lungs to carbon monoxide (DL_CO). Methods: Retrospective data were retrieved from electronical medical records of patients treated with Stereotactic Body Radiation Therapy (SBRT) at a single institution. Inclusion criteria were as follows: (1) SBRT treatment performed for primary early-stage non-small cell lung cancer (ES-NSCLC) or oligometastatic lung nodules, (2) availability of simulation four-dimensional computed tomography (4DCT) scan, (3) baseline spirometry data availability, (4) availability of baseline clinical data, and (5) written informed consent for the anonymized use of data. The gross tumor volume (GTV) was segmented on 4DCT reconstructed phases representing the moment of maximum inhalation and maximum exhalation (Phase 0 and Phase 50, respectively), and radiomic features were extracted from the lung parenchyma subtracting the lesion/s. An iterative algorithm was clustered based on correlation, while keeping only those most associated with baseline and post-treatment DL_CO. Three models were built to predict DL_CO abnormality: the clinical model—containing clinical information; the radiomic model—containing the radiomic score; the clinical-radiomic model—containing clinical information and the radiomic score. For the models just described, the following were constructed: Model 1 based on the features in Phase 0; Model 2 based on the features in Phase 50; Model 3 based on the difference between the two phases. The AUC was used to compare their performances. Results: A total of 98 patients met the inclusion criteria. The Charlson Comorbidity Index (CCI) scored as the clinical variable most associated with baseline DL_CO (p = 0.014), while the most associated features were mainly texture features and similar among the two phases. Clinical-radiomic models were the best at predicting both baseline and post-treatment abnormal DL_CO. In particular, the performances for the three clinical-radiomic models at predicting baseline abnormal DL_CO were AUC₁ = 0.72, AUC₂ = 0.72, and AUC₃ = 0.75, for Model 1, Model 2, and Model 3, respectively. Regarding the prediction of post-treatment abnormal DL_CO, the performances of the three clinical-radiomic models were AUC₁ = 0.91, AUC₂ = 0.91, and AUC₃ = 0.95, for Model 1, Model 2, and Model 3, respectively. Conclusions: This study demonstrates that radiomic features extracted from healthy lung parenchyma on a 4DCT scan are associated with baseline pulmonary function parameters, showing that radiomics can add a layer of information in surrogate models for lung function assessment. Preliminary results suggest the potential applicability of these models for predicting post-SBRT lung function, warranting validation in larger, prospective cohorts. Full article

Background/Objectives: Decision-analytic Bayesian approaches are ideally suited for designing clinical trials. They have been used increasingly over the last 30 years in developing medical devices and drugs. A prototype trial is a bandit problem in which treating participants is as important as treating patients in clinical practice after the trial. Methods: This article chronicles the use of the Bayesian approach in clinical trials motivated by bandit problems. It provides a comprehensive historical and practical review of Bayesian adaptive trials, with a focus on bandit-inspired designs. Results: The 20th century saw advances in Bayesian methodology involving computer simulation. In the 21st century, methods motivated by bandit problems have been applied in designing scores of actual clinical trials. Fifteen such trials are described. By far the most important Bayesian contributions in clinical trials are the abilities to observe the accumulating results and to modify the future course of the trial on the basis of these observations. In the spirit of artificial intelligence, algorithms are programmed to learn the optimal treatment assignments over the remainder of the trial. Conclusions: Bayesian trials are still nascent and represent a small minority of clinical trials, but their existence is changing the way investigators, regulators, and government and industry sponsors view innovation in clinical trials. Full article

Background/Objectives: “Ozempic face” is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27–65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert’s evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: “Ozempic face” is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Full article

Background and Objectives: We wished to evaluate the effect of antiresorptive agents (ARAs) on peri-implant tissues and to examine the risk factors for peri-implant medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: The study cohort consisted of patients who underwent implant surgery or maintenance treatment between March 2012 and December 2024. The patients were divided into two groups: those in whom bisphosphonates (BPs) or denosumab (Dmab) was used to treat osteoporosis after implant treatment (the ARA group) and a control group. Peri-implant clinical parameters (implant probing depth (iPPD), implant bleeding on probing (iBoP), marginal bone loss (MBL), and mandibular cortical index (MCI)) measured at the baseline and at the final visit were statistically evaluated and compared in both groups. Risk factors were examined using a multivariate analysis of adjusted odds ratios (aORs). Results: A total of 192 implants in 61 patients (52 female, 9 male) were included in this study. The ARA group consisted of 89 implants (22 patients). A comparison of the clinical parameters showed that the ARA group had significantly higher variations in their maximum iPPD and iBoP values over time than those in the control group. Risk factors for peri-implantitis as objective variables were the use of ARAs (aOR: 3.91; 95% confidence interval [CI]: 1.29–11.9) and the change in the maximum iPPD over time (aOR: 1.86; 95% CI: 0.754–4.58). Conclusions: During long-term implant maintenance treatment, patients’ health and medication status change. Monitoring peri-implantitis, the presumed cause of peri-implant MRONJ, is essential, especially in patients who started ARA treatment after implant placement, and special attention should be paid to changes in implant pocket depth. Full article

This review explores the potential of magistral formulas (MFs) as a viable option to meet the needs of neonates, given the lack of adequate therapies for this vulnerable group. The scientific literature on medicines available for neonates is limited. The physiological differences between neonates and adults make it difficult to formulate these medicines. In addition, there are a variety of difficulties in conducting research on neonates: few clinical trials are performed, and there is frequent use of unauthorized medicines. Pharmacokinetics in neonates was investigated in comparison to adults, and different aspects of the absorption, distribution, metabolism, and excretion were observed. One of the main problems is the different pharmacokinetics between the two populations. It is necessary to promote and allow research related to pediatric drug design, approve a specific authorization for use in age-appropriate dosage forms, and improve the quality and availability of information on drugs. This study focused on the MFs typically used for pediatrics, specifically for neonates, analyzing the pharmaceutical forms currently available and the presence of indications and dosage recommendations of the European Medicines Agency. Medications were classified according to therapeutic group, as antihypertensives, corticosteroids, and antiepileptics. The use of off-label medicines remains high in neonatal intensive care units and in primary healthcare, besides in the preparation of MFs by pharmacists. The shortage of medicines specifically designed and approved for neonates is a serious problem for society. Neonates continue to be treated, on numerous occasions, with off-label medicines. Studies and research should be expanded in this vulnerable population group. Full article

Background: Cucurbitacin E (CuE), a natural tetracyclic triterpenoid compound extracted from the melon stems of Cucurbitaceae plants, has been reported to exhibit anti-inflammatory and anti-cancer properties, along with the ability to enhance cellular immunity. However, its role and molecular mechanism in regulating lipid metabolism and adipogenesis remain unclear. This study aims to investigate the potential anti-adipogenic and anti-obesity effects of CuE in 3T3-L1 adipocytes. Materials and Methods: 3T3-L1 preadipocytes were cultured and induced to differentiate using a standard adipogenic cocktail containing dexamethasone, 3-isobutyl-1-methylxanthine (IBMX), and insulin (DMI). CuE was administered during the differentiation process at various concentrations. Lipid accumulation was assessed using Oil Red O staining, and cell viability was evaluated via the MTT assay. To determine whether CuE induced apoptosis or necrosis, flow cytometry was performed using annexin V/PI staining. Additional molecular analyses, such as Western blotting and RT-PCR, were used to examine the expression of key adipogenic markers. Results: Treatment with CuE significantly reduced lipid droplet formation in DMI-induced 3T3-L1 adipocytes in a dose-dependent manner, as shown by decreased Oil Red O staining. Importantly, CuE did not induce apoptosis or necrosis in 3T3-L1 cells at effective concentrations, indicating its safety toward normal adipocytes. Moreover, CuE treatment downregulated the expression of adipogenic markers such as PPARγ and C/EBPα at both mRNA and protein levels. Discussion: Our findings suggest that CuE exerts a non-cytotoxic inhibitory effect on adipocyte differentiation and lipid accumulation. This anti-adipogenic effect is likely mediated through the suppression of key transcription factors involved in adipogenesis. The absence of cytotoxicity supports the potential application of CuE as a safe bioactive compound for obesity management. Further investigation is warranted to elucidate the upstream signaling pathways and in vivo efficacy of CuE. Conclusions: Cucurbitacin E effectively inhibits adipogenesis in 3T3-L1 adipocytes without inducing cytotoxic effects, making it a promising candidate for the development of functional foods or therapeutic agents aimed at preventing or treating obesity. This study provides new insights into the molecular basis of CuE’s anti-obesity action and highlights its potential as a natural lipogenesis inhibitor. Full article

Background and Objectives: This study aimed to investigate the anticancer effects and potential synergistic interactions of quercetin (Q) and doxorubicin (Dox) on the MG-63 osteosarcoma (OS) cell line. Specifically, the effects of these agents on cell viability, apoptosis, reactive oxygen species (ROS) generation, antioxidant defense, and the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt1) signaling pathway were evaluated. Material and Methods: MG-63 cells were cultured and treated with varying concentrations of Q and Dox, both individually and in combination (fixed 5:1 molar ratio), for 48 h. Cell viability was assessed using an MTT assay, and IC₅₀ values were calculated. Synergistic effects were analyzed using the Chou–Talalay combination index (CI). Apoptosis was evaluated via Annexin V-FITC/PI staining and caspase-3/7 activity. ROS levels were quantified using DCFH-DA probe, and antioxidant enzymes (SOD, GPx) were measured spectrophotometrically. Gene expression (Runx2, PI3K, Akt1, caspase-3) was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Q and Dox reduced cell viability in a dose-dependent manner, with IC₅₀ values of 70.3 µM and 1.14 µM, respectively. The combination treatment exhibited synergistic cytotoxicity (CI < 1), especially in the Q50 + Dox5 group (CI = 0.23). Apoptosis was significantly enhanced in the combination group, evidenced by increased Annexin V positivity and caspase-3 activation. ROS levels were markedly elevated, while antioxidant enzyme activities declined. RT-qPCR revealed upregulation of caspase-3 and downregulation of Runx2, PI3K, and Akt1 mRNA levels. Conclusions: The combination of Q and Dox exerts synergistic anticancer effects in MG-63 OS cells by inducing apoptosis, elevating oxidative stress, suppressing antioxidant defense, and inhibiting the PI3K/Akt1 signaling pathway and Runx2 expression. These findings support the potential utility of Q as an adjuvant to enhance Dox efficacy in OS treatment. Full article

Background/Objectives: Primary malignant lung tumors in children are rare and diagnostically challenging. This study presents a single-center experience in the diagnosis and treatment of these tumors, emphasizing the role of histopathological and genetic profiling in informing individualized therapeutic strategies. Methods: We retrospectively reviewed records of seven pediatric patients (ages 2–18) treated from 2015 to 2025. Diagnostics included laboratory tests, chest CT, bronchoscopy, and histopathological/immunohistochemical analysis. Treatment primarily involved surgical resection, complemented by chemo-, radio-, or targeted therapies when indicated. Results: Inflammatory myofibroblastic tumor (IMT) represented the most commonly diagnosed entity (3/7 cases). The tumors presented with nonspecific symptoms, most frequently dry cough. Tumor type distribution was age-dependent, with aggressive forms such as pleuropulmonary blastoma predominantly affecting younger children, whereas IMT and carcinoid tumors were more common in older patients. Surgical resection remained the mainstay of treatment in the majority of cases. Bronchoscopy served as a valuable adjunct in the initial management of tumors exhibiting intraluminal growth, allowing for direct visualization, tissue sampling, and partial debulking to alleviate airway obstruction. In patients with an initially unresectable IMT harboring specific gene fusion rearrangement (e.g., TFG::ROS1), neoadjuvant targeted therapy with crizotinib enabled adequate tumor shrinkage to allow for subsequent surgical resection. Two patients in the study cohort died as a result of disease progression. Conclusions: A multidisciplinary diagnostic approach—integrating radiologic, bronchoscopic, histopathological, and genetic evaluations—ensures high diagnostic accuracy. While conventional treatments remain curative in many cases, targeted therapies directed at specific molecular alterations may offer essential therapeutic options for selected patients. Full article

The development of sustainable and functional nanocomposites has attracted considerable attention in recent years due to their broad spectrum of potential applications, including wood preservation. Also, a global goal is to reuse the large volumes of waste for environmental issues. In this context, the aim of the study was to obtain soda lignin particles, to graft ZnO nanoparticles onto their surface and to apply these hybrids, embedded into a biodegradable polymer matrix, as protection/preservation coating for oak wood. The organic–inorganic hybrids were characterized in terms of compositional, structural, thermal, and morphological properties that confirm the efficacy of soda lignin extraction and ZnO grafting by physical adsorption onto the decorating support and by weak interactions and coordination bonding between the components. The developed solution based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and lignin-ZnO was applied to oak wood specimens by brushing, and the improvement in hydrophobicity (evaluated by water absorption that decreased by 48.8% more than wood, humidity tests where the treated sample had a humidity of 4.734% in comparison with 34.911% for control, and contact angle of 97.8° vs. 80.5° for untreated wood) and UV and fungal attack protection, while maintaining the color and aspect of specimens, was sustained. L.ZnO are well dispersed into the polymer matrix, ensuring a smooth and less porous wood surface. According to the results, the obtained wood coating using both a biodegradable polymeric matrix and a waste-based preservative can be applied for protection against weathering degradation factors, with limited water uptake and swelling of the wood, UV shielding, reduced wood discoloration and photo-degradation, effective protection against fungi, and esthetic quality. Full article

Background/Objectives: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a major neglected tropical disease, with over six million cases concentrated, primarily in Latin America. Despite decades of research, treatment continues to rely on two outdated drugs—benznidazole and nifurtimox—both of which exhibit limited efficacy and are associated with severe side effects. In this context, drug repurposing presents a promising strategy to accelerate the development of safer and more effective therapies. Nitroxoline, a hydroxyquinoline compound widely used in Europe to treat bacterial urinary tract infections, has recently garnered attention for its broad-spectrum antimicrobial and anticancer activities. This study evaluated the antitrypanosomal potential of nitroxoline against both epimastigote and intracellular amastigote forms of T. cruzi, demonstrating significantly greater efficacy than benznidazole. Methods: In addition to its antiparasitic activity, we investigated the mechanism of parasite death and found that nitroxoline induces hallmarks of programmed cell death, including chromatin condensation, mitochondrial membrane depolarization, ATP depletion, reactive oxygen species accumulation, and increased membrane permeability. These cellular events are critical for minimizing host tissue inflammation and suggest a safer therapeutic profile. Results: The nitroxoline was shown to induce greater activity than the reference treatment, benznidazole, in addition to triggering events related to apoptotic or silent cell death. Conclusions: Given its established clinical use and favorable safety data, nitroxoline emerges as a strong candidate for further investigation as a repurposed treatment for Chagas disease. Future work should focus on in vivo efficacy, pharmacokinetics, and drug delivery strategies to enhance systemic bioavailability. Full article

Previous studies about the COVID-19 pandemic on STEMI patient outcomes have conflicting results. It remains unclear if this may be attributed to regional differences and/or differences during COVID-19 wave periods. Using the American Heart Association Get With The Guidelines–Coronary Artery Disease registry data, we evaluated (1) time metrics related to STEMI system goals and (2) regional variation in STEMI incidence and in-hospital mortality during pandemic wave time periods. The study included all patients 18–100 years old admitted with STEMI (n = 72,516) to 1 of 435 American Heart Association Get With The Guidelines–Coronary Artery Disease hospitals (1 October 2019–31 December 2021). Of these, 70.8% were male and 73.0% non-Hispanic White, with a median age of 63 (IQR 18) years. Compared to pre-pandemic time frames, patients with STEMI had a higher risk profile, delayed time to treatment, were treated with fibrinolytic therapy or primary PCI, and were transferred for primary PCI at similar rates, and had higher adjusted in-hospital mortality (during the second wave in the South and Midwest). Preservation of STEMI systems of care resulted in an overall lower in-hospital mortality rate than predicted, although opportunities exist to improve treatment delays. Regional differences in mortality rates require further study. Full article