Search Results (5,420)

High-entropy materials have emerged as promising candidates for high-temperature structural, magnetic, and electrochemical applications due to their unique combination of compositional complexity, thermal stability, and tailored functionality. In this study, self-propagating high-temperature synthesis (SHS) was employed to fabricate high-entropy composite in a Ti–Cr–Mn–Co–Ni–Al–C multicomponent system with a focus on elucidating the effect of titanium content on the combustion parameters, as well as on the phase and structure formation patterns of the resulting materials. In situ profiling enables evaluating the maximum combustion temperature of 1560 °C, combustion wave propagation velocity ranging from 0.22 to 4.3 mm/s depending on titanium content, and heating and cooling rates of 300–2000 °C/s and 3 °C/s during synthesis. The synthesized powders exhibited a bimodal particle size distribution, with ~90% of particles below 25 μm and a D50 of 5.38 μm. Post-synthesis densification via spark plasma sintering (SPS) at 1250 °C under 45 MPa yielded dense bulk samples, which exhibited a high relative density and high Vickers microhardness of 1270 ± 35 HV10 attributed to fine TiC dispersion and secondary carbide formation. Thermogravimetric analysis performed under air flow with a heating rate of 20 °C/min showed enhanced thermal stability for both the powder and the sintered bulk. These findings demonstrate the efficacy of SHS for rapid, energy-efficient fabrication of high-entropy composites and underscore the critical role of composition in tailoring their structural and mechanical properties. Full article

Lepidium meyenii Walpers (syn. Lepidium peruvianum Chacon) has been cultivated for centuries in the Peruvian Andes as both a vegetable and a traditional medicine resource. Maca is classified as a superfood and is widely used as a dietary supplement, particularly noted for its potential to enhance endurance, fertility, and endocrine balance. In recent years, there has been a growing interest in the cytotoxic effects of lepidilines and their derivatives; however, these compounds have been less extensively studied due to challenges associated with their isolation. This study aims to establish optimal extraction conditions to enrich lepidiline content in the extracts and to propose an efficient isolation method for four lepidilines using a green purification technique known as Centrifugal Partition Chromatography (CPC). The isolated compounds will be evaluated for their anticancer potential utilizing the MTT assay on SK-N-SH (ATCC^® HTB-11™) and SK-N-AS (ATCC^® CRL-2137™) neuroblastoma cell lines. The findings indicate that Soxhlet extraction with dichloromethane resulted in the highest recovery of lepidilines, with a content of 10.24% expressed as lepidiline A. The optimal biphasic solvent mixture suitable for CPC chromatographic applications was identified as a combination of chloroform, methanol, and water (4:3:2 v/v/v) containing 60 mM HCl. When utilized in conjunction with semi-preparative high-performance liquid chromatography (HPLC), this method successfully isolated lepidilines A–D, achieving a purity exceeding 95%. Notably, lepidiline B exhibited the highest cytotoxic potential, with an IC50 value of 14.85 µg/mL in SK-N-AS cells. Full article

Modern cosmology continues to struggle with unresolved questions concerning the origins of dark matter and dark energy. To explore these challenges, this study presents the Source Energy Field Theory (SEFT)—a new theoretical framework that offers an alternative view of how cosmic structures may form and evolve. SEFT envisions the universe as filled with a fundamental energy field, where the observed cosmological redshift does not result from accelerated expansion but rather emerges from the distance-dependent modulation of the energy field and the curvature produced by this field. To evaluate this idea, a nonlinear wave equation was developed to connect redshift with right ascension, declination, and distance. The model was optimized using 1701 observational data points from the Pantheon+ and SH0ES samples, which include Type Ia supernovae and Cepheid variables spanning distances from 6.3 to 17,241 Mpc. Its performance was compared with that of the standard ΛCDM model. SEFT achieved a slightly lower root-mean-square error (145.521 vs. 147.665 Mpc), a marginally higher determination coefficient (R² = 0.9910 vs. 0.9908), and significantly improved information criteria values (ΔAIC = −41.753, ΔBIC = −19.997). These results provide robust statistical support for SEFT and suggest that it can complement—and potentially extend—the ΛCDM paradigm in describing the structure and evolution of the universe. Full article

Protein misfolding diseases are characterized by structurally abnormal proteins that lose their functionality, resulting in cellular and tissue dysfunction. Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and Huntington’s disease, share a common etiopathogenesis characterize by the accumulation of misfolded proteins. These proteins autonomously aggregate within neuronal cells, triggering inflammation and cell death. The accumulation of misfolded proteins triggers endoplasmic reticulum (ER) stress, leading to alter Ca²⁺ homeostasis. This prolonged stress condition induces the cleavage of procaspase 4 which is resident in ER and activates NF-kB pathway activation, leading to inflammatory responses and cell death. In this study, the efficacy of the drug Vx-445 (Elexacaftor), used in the pharmacological treatment of cystic fibrosis, was assessed in human adenocarcinomic basal alveolar epithelial (A549) and neuronal (SH-SY5Y) cell lines, where ER stress was induced by Thapsigargin. The aim was to assess whether the corrector was able to reduce ER stress by restoring cellular homeostasis and, probably, the proper folding of misfolded proteins and reducing the inflammatory response triggered by these events. Therefore, protein levels of IkBα, p-STAT 3 and COXII were analyzed by flow cytofluorimetry, while Ca²⁺ content was measured by spectrofluorimetry. The results obtained suggest a significant effect of Vx-445 in restoring cellular homeostasis, leading to reduced expression of inflammation-related proteins, such as IL-6, tested by ELISA. Although preliminary, these results encourage further studies to explore the potential repurpose of Vx-445 as a therapeutic candidate for conditions involving ER stress and chronic inflammatory diseases associated with protein misfolding, beyond its current use in cystic fibrosis. Full article

Improper use of drugs in both animal and human therapy, such as doxycycline (DOX), lead to the accumulation of residues in edible animal tissues as well as in the environment. Plant-derived compounds reduce the adverse effects of drugs. This study aimed to evaluate the effect of cannabidiol (CBD) in two concentrations: lower (1.56 µg/mL) (DOX + C1) and higher (3.125 µg/mL) (DOX + C2) on the cytotoxicity of doxycycline in human cells. The toxicity of DOX and its CBD-containing mixtures was assessed after 72 h of exposure in three human cell lines: neural (SH-SY5Y), hepatic (HepG2), and kidney (HEK-293). The exposure to DOX resulted in inhibition of mitochondrial activity (SH-SY5Y) and inhibition of DNA synthesis (HepG2 and HEK-293). IC₅₀ values for DOX ranged from 9.8 to >200 µg/mL in SH-SY5Y cells, 13.4 to 200 µg/mL in HepG2 cells, and 8.9 to 30.4 µg/mL in HEK-293 cells. The nature of the interaction depended on both the cell lines and the concentration of CBD in the mixture. Both CBD mixtures demonstrated a synergistic interaction in neuronal cells. In HepG2 cells, both mixtures showed additive and antagonistic interactions. In HEK-293 cells, the DOX + C1 mixture exhibited an antagonistic (protective) effect, while the DOX + C2 mixture showed an additive effect. There were no changes in oxidative stress levels; however, alterations in apoptosis levels and cell morphology were observed following exposure to the mixtures. The presence of doxycycline in the diet and the environment poses a health risk to consumers. The increasing consumption of CBD-containing products may reduce the risk associated with the presence of this drug in food. It is worth emphasizing the need for research aimed at minimizing the adverse effects of pharmaceuticals on the health of humans and animals. Full article

This review integrates the biology and clinical translation of hydrogen sulfide (H₂S) in balneology. It frames H₂S as a gasotransmitters with dual chemical and biological actions and summarizes the H₂S/HS⁻ equilibrium as a function of pH, temperature, and oxygenation, which governs bioaccessibility in sulfurous waters. Endogenous and exogenous sources, transport, and mitochondrial catabolism are outlined, together with core cellular mechanisms: protein persulfidation; activation of Nrf2/ARE; modulation of NF-κB; regulation of ion channels; and engagement of PI3K/Akt, MAPK/ERK, and Wnt pathways, plus epigenetic interactions with HDACs and sirtuins. Preclinical and clinical evidence in dermatology, musculoskeletal disease, and respiratory care is synthesized, alongside metabolic, cardiovascular, gastrointestinal, and renal effects. Technical aspects that preserve the bioactive fraction of H₂S while meeting environmental safety limits are highlighted. Routes of administration (bathing, peloids, inhalation, and drinking cures) and key operational parameters are described. Overall, the review links physicochemical and molecular foundations with clinical indications for sulfurous waters and derivatives and identifies opportunities for research and development in H₂S donors and thermal cosmetics without extrapolating beyond the available data. Full article

Alzheimer’s disease (AD) is characterized by mitochondrial dysfunction, oxidative stress, insulin resistance, and aberrant protein aggregation. Neurodegeneration model with neuronal insulin resistance was induced in SH-SY5Y human neuroblastoma cells by streptozotocin (STZ). We evaluated the neuroprotective effects of resveratrol (RZV) and three structural analogs: oxyresveratrol (OXI), monomethyl resveratrol (MONO), and trimethyl resveratrol (TRI). Mitochondrial function, plasma membrane integrity, oxidative stress) and autophagy were studied by fluorescent assays. Phosphorylated GSK3 levels were measured by ELISA as an indicator of insulin sensitivity. TRI exhibited significant mitochondrial protective effects and strongly induced autophagy. OXI demonstrated excellent antioxidant activity but showed no detectable mitochondrial protective or autophagy-inducing effects. RZV and MONO exhibited moderate antioxidant effects along with strong insulin-sensitizing and autophagy-inducing properties. Insulin sensitivity was most potently restored by RZV (IC₅₀ = 54 pM) and MONO (IC₅₀ = 50 pM), whereas TRI (IC₅₀ = 160 pM) was less potent, and OXI (IC₅₀ = 97 pM) showed moderate potency. Our findings suggest that the neuroprotective effects of resveratrol analogs significantly depend on their molecular structure and that they exert their beneficial effects through distinct mechanisms. This research may contribute to the development of novel, multi-target compounds for the treatment of neurodegenerative diseases. Full article

Background/Objectives: The global aging population faces rising rates of cognitive decline and neurodegenerative disorders. This review explores how physical exercise influences brain health in aging, focusing on mechanisms, moderators, and personalized strategies to enhance cognitive resilience. Methods: A narrative review methodology was applied. Literature published between 2015 and 2025 was retrieved from PubMed, Scopus, and Web of Science using keywords and MeSH terms related to exercise, cognition, neuroplasticity, aging, and dementia. Inclusion criteria targeted peer-reviewed original studies in humans aged ≥60 years or aged animal models, examining exercise-induced cognitive or neurobiological outcomes. Results: Evidence shows that regular physical activity improves executive function, memory, and processing speed in older adults, including those with mild impairment or genetic risk (e.g., APOE ε4). Exercise promotes neuroplasticity through increased levels of BDNF, IGF-1, and irisin, and enhances brain structure and functional connectivity. It also improves glymphatic clearance and modulates inflammation and circadian rhythms. Myokines act as messengers between muscle and brain, mediating many of these effects. Cognitive benefits vary with exercise type, intensity, and individual factors such as age, sex, chronotype, and baseline fitness. Combined interventions—physical, cognitive, nutritional—show synergistic outcomes. Digital tools (e.g., tele-exercise, gamification) offer scalable ways to sustain engagement and cognitive function. Conclusions: Physical exercise is a key non-pharmacological strategy to support cognitive health in aging. It acts through diverse systemic, molecular, and neurofunctional pathways. Tailored exercise programs, informed by individual profiles and emerging technologies, hold promise for delaying or preventing cognitive decline. Full article

This study presents a numerical investigation into the structural behavior of a pile-in-pile (PIP) slip joint utilizing square hollow section (SHS) members, with a comparative assessment against conventional circular hollow sections (CHSs). A comprehensive finite element model was developed and validated against published CHS experimental results to evaluate key performance indicators, including stress distribution, buckling behavior, and load-carrying capacity under pure bending, axial compression, and diagonal lateral loads. The analysis revealed that SHS joints demonstrated distinct stress concentration patterns and higher capacity under axial compression, whereas CHS joints provided superior performance under bending due to their geometric symmetry. However, SHS corners were more vulnerable under diagonal loading, exhibiting localized buckling at relatively lower loads. These structural weaknesses can be mitigated through design improvements, such as increased wall thickness or corner strengthening. The findings highlight that while SHSs introduce certain vulnerabilities compared to CHSs, they also offer advantages in axial load resistance, supporting their potential as a viable alternative for offshore wind foundation connections. Full article

Background/Objectives: Honokiol (HK), a bioactive phenolic compound, exhibits significant anti-cancer properties. This study aimed to investigate the anti-cancer effects of HK in colorectal cancer (CRC) cells by focusing on its direct interaction with heat shock protein 27 (Hsp27) as a molecular target, and to elucidate the underlying mechanisms involved. Methods: HK was isolated via silica/ODS chromatography. Anchorage-independent growth of CRC cells was quantified using a soft agar assay with increasing HK concentrations. Apoptosis and cell cycle were analyzed by flow cytometry, and cell viability by MTS assay. Hsp27 binding to HK was validated by pull-down assay with HK-conjugated Sepharose 4B beads. Hsp27 knockdown was performed using lentiviral shRNA in CRC cells. Molecular docking of HK-Hsp27 interaction employed Schrödinger Suite 2016. Protein expressions, including chaperone and apoptotic proteins, were evaluated by Western blotting. Results: HK dose-dependently suppressed anchorage-independent growth of CRC cells and induced G₀/G₁ arrest. It triggered apoptosis through cytochrome c release, PARP cleavage, and Bcl-2 downregulation. HK directly bound to the α-crystallin domain of Hsp27 at Asn102 and His103 residues, confirmed by computational molecular docking and site-directed mutagenesis. Hsp27 knockdown in CRC cells dramatically reduced anchorage-independent growth. HK markedly decreased Hsp27 protein levels while having less effect on other heat shock proteins in CRC cells. Conclusions: HK exerts anti-cancer effects in CRC cells, associated with Hsp27 inhibition, resulting in suppressed cell growth and increased apoptosis. This interaction between HK and Hsp27 may support a mechanistic foundation supporting the potential utility of HK as a natural therapeutic agent for CRC. Full article

Maxillary sinus floor augmentation is frequently performed to increase bone height for dental implants, with stem cells suggested to boost bone regeneration. Consequently, this study aimed to assess the effects of incorporating stem cells in maxillary sinus floor augmentation. Two reviewers conducted an extensive search using a mix of controlled vocabulary (MeSH) and free-text terms to locate published systematic reviews. Searches were conducted in three major electronic databases (Medline via PubMed, Embase, and Cochrane database) up to July 2025. Initially, 250 articles were found, but only five studies met inclusion criteria for meta-analysis. The meta-analysis revealed a pooled standardized mean difference in new bone formation of 1.06 (95% confidence interval of −0.31 to 2.44). In a subgroup analysis comparing mesenchymal stem cells with autogenous bone, the pooled standardized mean difference was 0.88 (95% confidence interval of 0.34 to 1.42). The study’s results indicated a positive trend towards better outcomes with the use of mesenchymal stem cells, although the effect was not statistically significant at the pooled level. Additionally, combining stem cells with xenograft may yield more favorable results compared to using autogenous bone with xenograft. These findings suggest potential clinical advantages, highlighting the need for further standardized research to verify long-term outcomes. Full article

Secondhand smoke (SHS), found in about 57.6% of global public areas as a widespread environmental hazard, has been associated with negative effects during pregnancy, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Our research investigated the impact of SHS on placental issues in a C57BL/6 model that simulates PE and IUGR in mice. We administered SHS to pregnant mice through a nose-only delivery method, beginning either on embryonic day 12.5 (prior to spiral artery (SA) invasion; labeled SHS-6D) or day 14.5 (following SA invasion; labeled SHS-4D), continuing up to E18.5. Control animals received only ambient air. We employed bulk RNA sequencing to assess and describe changes in placental gene expression patterns. For the SHS-4D group, which mimicked IUGR, compared to untreated controls, results showed elevated levels of inflammation-related genes (IL11RA, CHI3L1) alongside likely interference in pathways for antibody-triggered complement activation, marked by reduced expression of C1QA, C1QB, and C1QC. Immune profiling also indicated decreased macrophage activity in the placentas of the SHS-4D group relative to those from normal pregnancies at term. In contrast, the SHS-6D versus control analysis revealed lowered expression of collagen-related genes (COL1A1, COL4A5, COL4A6, COL17A1). Additionally, SHS-6D exhibited higher levels of genes associated with cell-based lysis processes compared to SHS-4D. An evaluation of the existing literature revealed that nearly every differentially expressed gene (DEG) identified in our work has been reported in studies associated with SHS exposure. Yet, few of these DEGs are discussed alongside PE or IUGR in prior reports, highlighting gaps in knowledge about how SHS triggers these conditions. Overall, we determined that the timing of SHS exposure in pregnant mice results in unique patterns of gene regulation and involvement in biological pathways. Full article

Background/Objectives: Satoyoshi syndrome is a rare, autoimmune disorder currently diagnosed based on clinical criteria: painful muscle spasms, diarrhea, and alopecia. Two previous reports showed a specific immunoreactive band in three Satoyoshi syndrome patients using Western blot analysis, with brain homogenate as the antigen source. These findings could be the basis for a future diagnostic test. The aim of our study was to evaluate the efficacy of using SH-SY5Y cell lysate instead of brain homogenate for a potential laboratory test for Satoyoshi syndrome using the Western blot technique. Methods: Western blot analyses were conducted using brain homogenate, SH-SY5Y cell lysates, and differentiated SH-SY5Y cell lysates. Serum samples were obtained from three Satoyoshi syndrome patients, alongside control samples from thirty blood donors and six patients with other neurological conditions. Results: Sera from patients with Satoyoshi syndrome displayed a three-band pattern in the 70–100 kDa range. This pattern was reproducible across all tested antigen sources (brain homogenate, SH-SY5Y lysate, and differentiated SH-SY5Y lysate) but was not observed for the sera from the control groups. The bands were more visible when using either type of SH-SY5Y lysate compared to brain homogenate. No differences were found between the SH-SY5Y lysate and the differentiated SH-SY5Y lysate. Conclusions: Sera from our Satoyoshi syndrome patients showed a specific band pattern that could be used for a future evaluation of Satoyoshi syndrome using Western blot. The use of SH-SY5Y cell lysate vs. brain homogenate as an antigen source may improve visualization and reproducibility of the immunobands and be less costly. Full article

Background/Objectives: Neuroblastoma is a pediatric embryonal tumor of the autonomic nervous system, characterized by high heterogeneity. Recent research has explored the therapeutic potential of retinoic acid and selenium derivatives as antiproliferative agents. This study aims to assess the antiproliferative effects of sodium selenite and retinoic acid, as well as the conventional chemotherapeutic agents, cyclophosphamide and cisplatin, using the SH-SY5Y neuroblastoma cell line. Methods: Cells were treated with the compounds at concentrations ranging from 0 to 1000 µM for 72 h. The following assays were performed: cell viability, clonogenic assay, cell migration, cell cycle analysis, and gene expression (BCL2 and BAX). Data were analyzed using the Kruskal–Wallis test followed by Dunn’s or the Mann–Whitney test (p < 0.05). IC₅₀ values were obtained from dose–response curves. Results: Sodium selenite (100–1000 µM) significantly reduced cell viability by more than 50% (IC₅₀: 166 µM at 72 h). Retinoic acid (300 µM) reduced viability by 65% (IC₅₀: 198 µM at 72 h), and cisplatin (10 µM) reduced viability by 79% (IC₅₀: 3.4 µM at 72 h). All compounds significantly decreased colony formation. Sodium selenite and retinoic acid induced arrest in the G0/G1 phase of the cell cycle. Gene expression analysis revealed downregulation of the BCL2 gene by all compounds and upregulation of BAX only by sodium selenite at IC₅₀ concentration. Conclusions: Sodium selenite and retinoic acid showed antiproliferative effects on neuroblastoma cells, suggesting their potential as adjuvant therapeutic agents. To reach this goal, we suggest further investigation of their mechanisms of action and evaluation of the combined strategies. Full article

Objectives: This systematic review analyzed the root canal morphology and configuration (RCC) of maxillary first premolars (Mx1Ps) and sex-specific differences based on existing literature. Methods: Registered in PROSPERO (CRD42023394460) and following PRISMA guidelines, systematic searches were conducted in five databases (Cochrane, Embase, LILACS, Scopus, MEDLINE via PubMed) using predefined MeSH terms. Additional studies were identified through cross-referencing. Studies on Mx1P RCCs were included, assessed using the AQUA tool. Data extraction focused on RCC prevalence, sex differences, root variations, and examination methods. Results: Of 865 studies, 86 were included, analyzing 31,325 teeth. The most common RCCs were 2-2-2/2 (IV, frequencies between 0.6–80.5%) and 1-1-1/1 (I, 1.1–72.0%). Mx1Ps primarily had two roots (7.1–96.2%) or one root (3.8–93.2%), with three-rooted variants being rare (0.4–6.5%). Males more frequently exhibited two- or three-rooted Mx1Ps with RCCs like 2-2-2/2 (IV; OR = 1.39 [1.22, 1.58]), and 1-1-3/3 (VIII; OR = 2.22 [1.59, 3.11]). Females showed higher frequencies of RCCs like 1-1-1/1 (I; OR = 0.71 [0.53, 0.96]), 2-2-1/1 (II; OR = 0.66 [0.57, 0.77]), 1-2-1/1 (III; OR = 0.70 [0.59, 0.83]), and 1-1-2/2 (V; OR = 0.81 [0.70, 0.95]). Conclusions: Mx1Ps predominantly have two roots and a 2-2-2/2 (IV) RCC. CBCT was the most used method, followed by staining and clearing. Clinicians should consider sex-specific and morphological variations. Full article