Search Results (29,169)

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder driven by complex interactions between protein aggregation, oxidative stress, neuroinflammation, and cellular dysfunction. Among plant-derived compounds, curcumin has emerged as one of the most extensively studied polyphenols due to its broad spectrum of biological activities. This review provides a critical synthesis of the mechanistic, preclinical, and clinical evidence on curcumin in AD. Experimental studies consistently demonstrate that curcumin modulates key pathogenic processes, including neuroinflammatory signaling, oxidative stress, and amyloid-β aggregation, with more limited evidence for effects on tau pathology. While in vitro studies offer detailed mechanistic insights, in vivo models provide more integrated evidence, including improvements in cognitive performance and reductions in pathological markers. Despite this strong preclinical foundation, the clinical evidence remains limited and inconsistent. Randomized controlled trials have not demonstrated clear therapeutic efficacy, with outcomes strongly influenced by formulation, bioavailability, and study design. Poor solubility, rapid metabolism, and limited brain exposure remain key translational barriers. In response, increasing attention has been directed toward formulation strategies and structurally related compounds. Emerging curcuminoids, such as bisdemethoxycurcumin (BDMC), are discussed as potential next-generation candidates. Preliminary evidence suggests that BDMC may modulate oxidative stress, autophagy, astrocyte senescence, and amyloid-related processes, although the data remain largely preclinical. Overall, curcumin represents a mechanistically rich and preclinically promising multi-target compound but with unresolved translational limitations. Future research should prioritize pharmacokinetic optimization, formulation-dependent validation, and exploration of novel curcuminoid strategies to bridge the gap between experimental findings and clinical application in AD. Full article

The Fukushima nuclear accident caused widespread radiocesium contamination, and subsequent decontamination reduced soil fertility by removing nutrient-rich topsoil. Although biological amendments have been widely investigated for soil improvement, their potential to restore crop productivity in decontaminated Fukushima soils remains poorly understood. This study evaluated a Bacillus-based biofertilizer (Yume-Bio) and an Aspergillus fermentation product (kouji) as biological amendments for restoring crop productivity in decontaminated soils. Pot and field experiments were conducted to assess their effects on the growth, mineral nutrition, and seed yield of Perilla frutescens grown in decontaminated Fukushima soils. In pot experiments, Yume-Bio showed no significant effects on plant growth, although slight root improvement was observed. In contrast, application of kouji alone or in combination with Yume-Bio significantly enhanced plant growth, increasing leaf number by 112% and improving biomass production. Nutrient accumulation was also promoted, with total N and Fe increasing by 170% and 194%, respectively. In field experiments at two sites in Fukushima, treatment effects were limited and generally non-significant. These results indicate that kouji has potential to enhance plant growth under controlled conditions, while the effectiveness of biological amendments under field conditions remains site-dependent, highlighting the need to optimize application strategies under heterogeneous soil conditions. Full article

Background/Objectives: Calcium hydroxyapatite (CaHA)-based injectable materials are widely used as dermal biostimulators. In vitro models allow for controlled comparison of cellular responses and particle characteristics across formulations. This study aimed to compare two commercially available CaHA-based materials in terms of fibroblast metabolic activity, extracellular matrix-related gene expression, and microsphere morphology. Methods: Primary human dermal fibroblasts were exposed to two CaHA-based materials (Sample R and Sample S) at 10 mg/mL. Metabolic activity was assessed using the MTT assay at 24, 36, 48, and 72 h. Type I collagen and elastin gene expression were evaluated by RT-qPCR at 72 h. Microsphere morphology was analyzed by scanning electron microscopy (SEM). Results: Both materials increased fibroblast metabolic activity compared with the control at all time points. Early responses were similar, whereas Sample S showed higher activity at 48 and 72 h. At 72 h, both materials increased collagen and elastin gene expression versus the control, with greater responses observed for Sample S. SEM analysis showed predominantly spherical microspheres in both materials, with qualitative differences in surface microtopography. Conclusions: Under controlled in vitro conditions, both CaHA-based materials were biocompatible and modulated fibroblast metabolic activity and extracellular matrix-related gene expression. Differences in particle surface characteristics may contribute to the observed biological profiles. These findings support further studies incorporating extended incubation periods and protein-level analyses. Full article

Multifunctional drugs represent an emerging strategy for treating complex skin disorders and melanoma. A series of benzothiazole-based hybrids incorporating gallic and syringic acid moieties was synthesized and evaluated as multifunctional agents for skin-related applications. Six hydrazone (GAHYDR1–3) and acyl-hydrazone (GACIN1–3) derivatives were obtained and fully characterized. Hydroxylated compounds showed the strongest antioxidant activity, with GAHYDR1 and GACIN1 displaying low DPPH IC₅₀ values and high FRAP reducing power. UV–Vis studies revealed strong UVA–UVB absorption, with molar extinction coefficients comparable to or exceeding those of PBSA. Photoprotective evaluation showed SPF values up to 10.09 (GACIN2) and broad-spectrum behavior for selected derivatives. Antioxidant activity remained substantially stable over 3 months in solution. Antiproliferative assays against Colo38, A375, and HaCaT cell lines indicated generally low cytotoxicity toward non-tumor cells. Notably, GAHYDR3 exhibited selective activity against A375 melanoma cells (IC₅₀ = 8.75 µM; SI = 8.12). Overall, phenolic substitution emerged as a key determinant of biological activity, highlighting hydroxylated benzothiazole hybrids as promising antioxidant and photoprotective agents, with GAHYDR3 representing a potential lead for anti-melanoma development. Full article

KCTD proteins exhibit significant structural complexity, arising from their modular organization, oligomerization, and intricate biological partnerships. Although their biological importance has been assessed for two decades, the biochemical basis of their activities is only partially understood. This is certainly due to the limited structural information that was available until a few years ago. Fortunately, some recent insightful structural studies and the advent of machine-learning-based approaches are rapidly changing the scenario. By surveying the literature and structural databases and integrating this information with ad hoc 3D-structure predictions, we provide a detailed view of the structural biology of these proteins at different levels: individual domains, full-length oligomers, functional hetero-oligomers formed by different family members, and complexes with functional partners. Collectively, these surveys and analyses provide insights into the family’s evolutionary history and its structure–function relationships. The family-wide coverage of structural information also indicates the extent to which structural similarities are reflected in functional analogies. Finally, the potential functional implications of the intricate architecture of these multimeric proteins and the tendency of their members to hetero-oligomerize are discussed from a functional perspective. Full article

As the world moves toward a circular bioeconomy, starch nanoparticles (SNPs) have emerged as key components for sustainable development. Traditional production methods have historically relied on harsh acid treatments; however, their substantial environmental footprint has catalyzed a much-needed shift toward “green” chemistry. This review explores the rise of eco-friendly synthesis strategies—including high-power ultrasound, mechanical milling, nanoprecipitation, and enzymatic hydrolysis—and explains how these “clean” methods allow us to precisely define the nanoparticles’ properties. Furthermore, the functional applications of SNPs are analyzed, focusing on their role as reinforcing agents in biodegradable packaging, natural stabilizers in food emulsions, and encapsulation matrices for targeted nutrient delivery. By connecting recent breakthroughs, this work identifies technological synergy, the integration of physical and biological methods, as the most promising route to overcome current yield and scalability limitations. Finally, a future perspective is proposed, focusing on what is needed to move these innovations from the lab to industrial applications, ensuring they are safe, effective, and truly sustainable for the global food sector. Full article

Background/Objectives: The “Land of Fires” (LF) in the Campania Region has attracted considerable attention due to massive environmental contamination deriving from decades of illegal disposal, burial, and burning of urban, industrial, and toxic waste. Cadmium (Cd) has been repeatedly proven to affect male reproductive function by a plethora of endocrine and non-endocrine mechanisms. The scientific literature is almost devoid of large studies addressing semen quality in this area, particularly by directly correlating seminal parameters to objectively measured pollutant burden in biological samples. Therefore, the aim of the current study was to comprehensively evaluate semen quality of males of reproductive age living in the LF, by correlating seminal parameters to cumulative local male reproductive tract Cd burden objectively quantified in whole semen samples. Methods: The current single-center, observational, cross-sectional study evaluated semen quality in 493 males aged 14–50 (29.07 ± 7.17) years living in three LF municipalities. Moreover, the association of semen quality with whole semen Cd (sCd) levels measured by inductively coupled plasma mass spectrometry (ICP-MS) was addressed in a subgroup of participants; semen samples suitable for semen Cd measurements were available from 383/493 (77.7%) participants of the total cohort, and all analyses involving semen Cd were performed within the measured subset. Results: In the total cohort, seminal parameters were as follows: semen pH 8.32 ± 0.3, semen volume 3.13 ± 1.67 mL, sperm concentration 37.58 ± 30.18 × 10⁶/mL, total count 111.2 ± 104 × 10⁶/ejaculate, total motility 56.83 ± 16.09%, progressive motility 50.22 ± 16.63%, in situ motility 6.72 ± 3.43%, immotile spermatozoa 43.07 ± 15.88%, normal morphology 7.97 ± 4.02%, and viability 64.75 ± 15.34%. Prevalence of normozoospermia and pathological seminal parameters was as follows: normozoospermia 66.5% (328/493), pathological seminal parameters 33.5% (165/493), specifically, oligozoospermia 14% (69/493), cryptozoospermia 0.8% (4/493), azoospermia 2.2% (11/493), asthenozoospermia 3% (15/493), teratozoospermia 0.6% (3/493), oligo-astheno-teratozoospermia 6.1% (30/493), necrozoospermia 5.7% (28/493), and different combined seminal parameters alterations 7.1% (35/493). Whole semen Cd was below (undetectable) or above (detectable) the limit of detection (LoD) (0.2 μg/L) in 66.6% (255/383) and 33.4% (128/383) whole semen samples, respectively. In samples with detectable sCd, sCd level was below or above the median value (0.76 μg/L; min–max 0.1–5.95 μg/L) in 23.4% (30/128) and 76.6% (98/128) whole semen samples, respectively. Participants with detectable sCd levels had a significantly reduced sperm total count (93.28 ± 84.88 × 10⁶/ejaculate vs. 113.2 ± 101.5 × 10⁶/ejaculate; p = 0.037), and normal morphology (7.29 ± 3.71% vs. 8.23 ± 3.91%; p = 0.034), and a significantly lower prevalence of normozoospermia (60.2% vs. 72.2%; p = 0.02) and significantly higher prevalence of pathological seminal parameters (39.8% vs. 27.8%; p = 0.02), specifically, a significantly higher prevalence of oligozoospermia (21.1% vs. 12.6%; p = 0.036) than those with undetectable sCd levels. Whole semen Cd levels were significantly higher in participants with pathological seminal parameters (1.08 ± 0.84 μg/L vs. 0.93 ± 0.74 μg/L; p = 0.037) than those with normozoospermia. Participants with sCd levels above the median value (N = 98) had a significantly reduced sperm concentration (29.12 ± 24.84 × 10⁶/mL vs. 43.62 ± 29.55 × 10⁶/mL; p = 0.015) and displayed a trend towards reduced sperm normal morphology (6.92 ± 3.38% vs. 8.55 ± 4.49%; p = 0.057) than those with sCd levels below the median value (N = 30). Moreover, participants with sCd levels above the median value (N = 98) had a significantly reduced sperm concentration (29.12 ± 24.84 × 10⁶/mL vs. 35.3 ± 26.29 × 10⁶/mL; p = 0.03), total count (85.77 ± 80.52 × 10⁶/ejaculate vs. 113.2 ± 101.5 × 10⁶/ejaculate; p = 0.008) and normal morphology (6.92 ± 3.38% vs. 8.23 ± 3.91%; p = 0.006), and a significantly lower prevalence of normozoospermia (57.1% vs. 72.2%; p = 0.008) and significantly higher prevalence of pathological seminal (42.9% vs. 27.8%; p = 0.008), specifically, a significantly higher prevalence of oligozoospermia (23.5% vs. 12.6%; p = 0.014) than those with undetectable sCd levels. Conclusions: The results of the current study demonstrate an association between the environmental Cd exposure and the impairment of seminal parameters, with a significantly poorer semen quality in participants with detectable sCd, and, more markedly, in those with sCd level above the median value, compared to participants with undetectable sCd, although subgroups comparisons highlighted a homogeneous profile in major confounders including age, BMI, and smoking habits among subgroups of participants with different sCd burden. Full article

Platelet-rich fibrin (PRF) has been widely used in regenerative dentistry because of its potential to support tissue regeneration. Recently, modifications in PRF preparation protocols and tube surface characteristics have attracted attention because of their possible influence on fibrin organization and biologic activity. The present in vitro study aimed to evaluate the effects of nano-hydroxyapatite platelet-rich fibrin (HA-PRF) on gingiva-derived mesenchymal stem cells (GMSCs) by comparing it with leukocyte platelet-rich fibrin (L-PRF) and titanium platelet-rich fibrin (T-PRF). Gingival tissue and venous blood samples were obtained from a systemically healthy male volunteer. PRF membranes were prepared using conventional glass tubes, nano-hydroxyapatite-coated tubes, and titanium tubes. GMSCs were isolated, characterized, and cultured with PRF membranes. Cell viability and metabolic activity were evaluated using MTT analysis. Apoptosis and necrosis rates were assessed by Annexin V/PI flow cytometry. VEGF and TGF-β1 release levels were determined by ELISA, whereas IL-1β, IL-6, and TNF-α gene expression levels were analyzed using qRT-PCR. The HA-PRF and L-PRF groups demonstrated higher cell viability values compared with the T-PRF group on day 7. Annexin V/PI analysis revealed no statistically significant differences between the groups in terms of apoptosis and necrosis. Growth factor release and cytokine gene expression profiles demonstrated time-dependent biologic responses in all PRF membranes. Within the limitations of this study, HA-PRF showed no evidence of cytotoxicity and demonstrated biologic responses comparable to those observed with conventional L-PRF. Both HA-PRF and L-PRF generally exhibited more favorable cellular responses than T-PRF under the present experimental conditions. Full article

Since its introduction in 1976, the Bradford assay has served as a gold standard for protein quantification across a wide range of applications. While its limitations—including protein-to-protein variation in dye binding, challenges in selecting a representative calibration standard, and susceptibility to matrix interferences—are recognized, the relevant information remains scattered throughout the literature, with little quantitative guidance available for assay optimization. Here, we review interfering compounds reported in the literature during nearly 50 years and report a systematic characterization of a panel of potential interfering compounds, evaluating the effects of 29 different substances in the presence or absence of the protein analytes. Our findings revealed that 12 of the tested compounds induce significant artefacts in the Bradford assay, with minimal interfering concentrations varying widely across compounds. Detergents were confirmed as the most problematic interference; furthermore, two novel groups of interfering compounds were identified, represented by the transfection reagents and oligoarginine peptides with molecular weight below 3 kDa. Importantly, the resulting artefacts were also observed in complex biological matrices. While these compounds also affected the Lowry assay, the magnitude of the artefacts was substantially lower than that observed in the Bradford assay. This study will provide a valuable resource for researchers working in proteomics and related fields, offering practical insights for improving the reliability of Bradford-based protein quantification. Full article

Mitochondrial Lon peptidase 1 (LONP1) is an ATP-dependent AAA⁺ (ATPases associated with diverse cellular activities) protease that has emerged as a key regulator of mitochondrial proteostasis, with functions extending beyond protein quality control. In addition to degrading misfolded and oxidized proteins, LONP1 coordinates mitochondrial DNA maintenance, metabolic remodeling, and stress-responsive signaling. Recent structural and functional advances have expanded the biological significance of LONP1 beyond protein quality control, highlighting its roles in mitochondrial metabolism, genome maintenance, and stress responses. LONP1 dysregulation is increasingly implicated in cancer, metabolic disorders, neurodegeneration, and aging, where it exerts context-dependent effects on cell survival and disease progression. In cancer, LONP1 supports metabolic plasticity, redox adaptation, and therapeutic resistance, whereas in degenerative conditions, its decline contributes to mitochondrial dysfunction and tissue damage. Here, we synthesize recent insights into the structure, mechanisms, and biological functions of LONP1 and discuss their implications for human disease. We further discuss emerging therapeutic strategies and key challenges for targeting LONP1 in human disease. Full article

Surgical intervention in Crohn’s disease remains a significant contributor to patient morbidity, with postoperative complication rates reported between 20% and 50%. These complications include a broad spectrum of adverse outcomes, such as surgical site infections, intra-abdominal abscesses, and anastomotic leakage, all of which can substantially impact recovery, healthcare costs, and long-term prognosis. Although several clinical and perioperative risk factors have been identified, accurate prediction of postoperative outcomes remains challenging, highlighting the need for improved risk stratification strategies. In recent years, the evolution of biological therapies has transformed the management of Crohn’s disease, raising important questions regarding their influence on surgical outcomes and postoperative healing. Consequently, a more nuanced understanding of the interplay between medical and surgical approaches is required to optimize patient care. This systematic review aims to evaluate established and emerging predictive biomarkers associated with postoperative complications in Crohn’s disease surgery. Particular emphasis is placed on inflammatory markers, nutritional parameters, and novel molecular signatures. Furthermore, the review explores the growing role of multiomics approaches—including genomics, proteomics, and metabolomics—as well as the integration of machine learning models to enhance predictive accuracy. By synthesizing current evidence, this study underscores the potential of combining biomarkers with advanced analytical tools to support personalized risk assessment and guide clinical decision-making in Crohn’s disease surgery. Full article

Background: Ventral hernias are a common complication following abdominal surgery, occurring in up to 20% of patients after midline laparotomy and as many as 43% of those who undergo orthotopic liver transplantation (OLT). These hernias pose unique challenges due to chronic immunosuppression, impaired wound healing, and the anatomic disruption caused by subcostal and “Mercedes-Benz” incisions. As survival after OLT continues to improve, the need for durable, infection-resistant abdominal wall reconstruction has become increasingly important. Methods: We performed a single-institution retrospective review of all OLT patients undergoing abdominal wall reconstruction by the senior author between June 2014 and April 2026. Our approach emphasizes component separation to reestablish myofascial continuity, biologic onlay reinforcement with human acellular dermal matrix (HADM), and multipoint fixation in a progressive tension pattern. Results: Forty patients (43 encounters) were included. Mean age was 55.7 ± 10.2 years, mean BMI was 31.2 ± 4.9 kg/m², and 60.0% were obese. The majority presented with recurrent hernias (67.4%), and 41.9% had prior mesh in situ. Component separation was performed in all cases, and intraoperative Botox in 18.6%. HADM was used in 83.7% of encounters. At a mean follow-up of 34.0 months, there was 1 hernia recurrence (2.3%). The surgical site occurrence rate was 14.0%, with seroma as the most common complication (9.3%). There were no 30-day mortalities. Conclusions: By integrating biologic and mechanical principles, this reconstructive strategy provides a durable solution for abdominal wall repair in liver transplant recipients. A 2.3% recurrence rate and 14.0% surgical site occurrence rate compare favorably to published benchmarks in the transplant population. Full article

Oxidative stress has been recognized as a repeatedly validated pathophysiological factor in schizophrenia, but its mechanistic role and translational relevance remain incompletely defined. Prior work has advanced redox dysregulation, neuroinflammation, and NMDA receptor hypofunction as a putative central hub in schizophrenia. This narrative review proposes an evidence-weighted redox–mitochondria–immune framework that integrates peripheral biomarkers, magnetic resonance spectroscopy, postmortem findings, and preclinical mechanisms while explicitly distinguishing established observations from candidate pathways. Existing studies support increased oxidative damage and altered antioxidant buffering in schizophrenia, particularly involving the glutathione system. However, these abnormalities are neither uniform across disease stages nor equally represented across patient subgroups, and may be markedly prominent only in certain biological subgroups. Mechanistically, redox imbalance may interact with mitochondrial bioenergetic deficits and innate immune signaling; however, pathway-specific links such as cGAS-STING activation, nitrosative/peroxynitrite stress, and GPx4-ferroptosis should currently be treated as testable extensions rather than validated human mechanisms in schizophrenia. Importantly, the pathological consequences of oxidative stress are unlikely to be cell-type neutral. Parvalbumin-positive interneurons and oligodendrocyte lineage cells are more vulnerable because of their high metabolic load, limited antioxidant buffering capacity, and lipid/iron-related susceptibility, thereby providing a mechanistic bridge to excitation–inhibition imbalance, myelin abnormalities, and reduced circuit synchrony. Microglial redox–inflammatory signaling may further exacerbate these processes. On the basis of this framework, we argue that the key for future research is not to continue demonstrating the universality of oxidative stress, but to improve the translational efficiency. Biomarker-guided stratification, stage-sensitive study designs, and cell-type-informed therapeutic strategies may therefore provide a more productive path toward redox-targeted interventions in schizophrenia. Full article

Maternal exposure to airborne particulate matter smaller than $2.5$ μm (${\mathrm{PM}}_{2.5}$) has been associated with adverse fetal outcomes, although its effects on intramembranous ossification remain poorly understood. This study evaluated the impact of gestational and pregestational exposure to wood-smoke-derived ${\mathrm{PM}}_{2.5}$ on fetal neurocranial ossification in Sprague–Dawley rats. Females were allocated to four exposure conditions combining filtered air (FA) and non-filtered air (NFA): FA/FA, FA/NFA, NFA/FA, and NFA/NFA. Fetuses were collected at gestational day 21 and analyzed using fetal morphometry, radiography, micro-computed tomography, whole-mount alizarin red skeletal staining, histology, and immunohistochemistry for HIF-1$\alpha$, COL-1, BMP-2, FGF-R1, and TGF-$\beta$. Continuous exposure (NFA/NFA) was associated with reduced fetal weight, shorter crown–rump length, impaired craniofacial mineralization, widened cranial sutural regions, and reduced mineral density, particularly in the occipital and interparietal bones. Histologically, exposed fetuses exhibited abundant osteoid, reduced osteocyte incorporation, and diffuse osteoblastic distribution, consistent with delayed osteogenic maturation. Immunohistochemistry showed increased HIF-1$\alpha$ immunoreactivity, altered TGF-$\beta$ regulation, and reduced COL-1 expression in continuously exposed fetuses, whereas BMP-2 and FGF-R1 showed no significant changes. These findings suggest that maternal exposure to wood-smoke-derived PM_2.5 is associated with delayed fetal neurocranial intramembranous ossification, particularly under continuous exposure. The observed immunohistochemical profile, elevated HIF-1$\alpha$, reduced COL-I, and altered TGF-$\beta$, is consistent with a hypoxia-associated imbalance between extracellular matrix deposition and mineral maturation; however, the underlying mechanistic pathway was not directly functionally tested and should be regarded as a biologically plausible inferential model requiring further experimental validation. Full article

Background/Objectives: Adenomyosis is a common estrogen-dependent gynecological condition with a largely undefined genetic architecture. Ciliary dysfunction has been implicated in its pathogenesis, positioning genes governing ciliary structure and motility as biologically plausible candidates for investigation. The DNAH5 gene encodes a critical component of the outer dynein arms within the ciliary axoneme, and pathogenic variants are among the most common causes of primary ciliary dyskinesia. This study aimed to systematically determine the frequency of a novel synonymous DNAH5 variant, NM_001369.3:c.9258C>T, p.(Leu3086=), in a large, histopathologically confirmed sporadic adenomyosis cohort from Turkiye, and to evaluate its occurrence relative to population-level reference data. Methods: A total of 121 women with histopathologically confirmed adenomyosis following hysterectomy were enrolled. Sanger sequencing was performed under stringent quality control conditions, including primer specificity verification by NCBI BLAST and UCSC In Silico PCR. Variant frequency was compared against gnomAD v4.0 and an in-house Turkish exome database (NGS Cloud; ~30,000 sequences) using Fisher’s exact test. In silico splice site analysis was performed using SpliceAI, and variant classification followed ACMG/AMP guidelines. Results: The variant was detected in 63 of 121 patients (52.1%; 95% CI: 43.1–61.0%), exclusively in the heterozygous state; no homozygous carriers were identified. The variant was absent from both gnomAD v4.0 across all populations and the NGS Cloud Turkish exome database (MAF: 0.0000), yielding a frequency difference (p < 2.2 × 10⁻¹⁶). SpliceAI analysis predicted no significant splice site impact (all delta scores < 0.1). The variant was classified as a variant of uncertain significance (VUS; BP7, PM2_supporting). Conclusions: This study identifies a difference in the frequency of a novel synonymous DNAH5 variant between a histopathologically confirmed adenomyosis cohort from Turkiye and population-level reference datasets, in which the variant was absent. Given the unphenotyped nature of the reference dataset, these findings are hypothesis-generating and do not establish a causal genetic association. Replication in independent cohorts and functional studies are warranted to elucidate the biological significance of this variant in adenomyosis susceptibility. Full article