Search Results (1,880)

Abnormalities were observed in the testes of common carp Cyprinus carpio collected from Willow Beach, Arizona, USA, a site on the lower Colorado River, downstream of Lake Mead and Hoover Dam. Testicular tissue collected from this site in 2003 exhibited numerous large, pigmented macrophage aggregates (MAs) and a novel, previously undescribed hypertrophy and proliferation of putative Sertoli cells. In testes samples collected in 2007, numerous testicular MA, testicular oocytes, and proliferations of Sertoli cells were observed. Three carp collected in 2007 also had raised nodules within the testes, and, microscopically, seminoma, spermatogenic seminoma, and mixed stromal cell–germ cell neoplasms were diagnosed. Several risk factors for these adverse effects were identified. Carp collected at this site in 2003 ranged in age from 35 to 54 years and had the oldest mean age of the thirteen sites sampled within the Colorado River basin. This site also has an unusual thermal regime when compared to other sites studied in Lake Mead and upstream sites, in that temperatures varied little over the seasons (amplitude around 1.5 °C) and barely reached 15 °C. Additionally, carp from this site had the highest total polychlorinated biphenyl (PCB) body burden. Hence, advanced age, low water temperature, and exposure to PCBs and other environmental contaminants may contribute to the observed abnormalities, highlighting the complex environmental factors initiating pre-neoplastic and neoplastic changes in wild carp. Full article

The goal of this paper is to assess the evolution of the autogenous strains as well as the thermal strains (thanks to the assessment of the coefficient of thermal expansion) of alkali-activated slag-based materials at early age. The effect of the sand and the coarse aggregates on the paste and mortar scale to upscale to mortar and concrete, respectively, has been investigated as a function of the age of the material. The restraint imposed by the sand on the paste seemed more significant than that of the coarse aggregate on the mortar. In addition, the long-term autogenous strains have been monitored on the mortar scale. These results revealed a separation into groups based on the solution concentration. Different testing methods were also compared. Thermal and autogenous strains were monitored with a customized testing device where the thermal variations are controlled. These devices were the horizontal corrugated tubes method (for tests on paste and mortar scales) and the vertical corrugated tubes method (for tests on mortar and concrete scales). Depending on the compositions (lower concentration), good correlations can be obtained between the two testing methods. Moreover, the autogenous strain of two different specimen sizes was also assessed manually (initially for the long-term), but early-age comparison showed good correlation for lower solution-to-binder ratios. On the concrete scale, a correlation based on the modified equations from the standards was established between the compressive strength and the tensile strength, obtained from the splitting tensile test. Full article

Background: Pain is a common but often under-recognized clinical feature among children and young people (CYP) cancer survivors. This systematic review aimed to examine the prevalence of acute and chronic pain in 5–24-year-old cancer survivors, explore associated biopsychosocial comorbidities and evaluate the psychometric properties of pain assessment tools used with this population. Methods: This review provides a conceptual replication to a review published in 2020 by Schulte et al. by updating and purposefully narrowing the review population to CYP (5–24 y) to better capture their pain experience. We updated the search from Schulte et al., extending the search period up to October 2024 across 5 databases. Results: Our independent search identified 18 studies, with only 1 new paper published since Schulte et al., 2020. Overall, CYP cancer survivors reported a higher prevalence of pain than the general population, with females experiencing higher levels than males, consistent with broader chronic pain literature. Fatigue, depression, and anxiety were common comorbidities, and pain substantially impacted quality of life. Key limitations included the use of unvalidated questionnaires; inconsistent definitions of chronic pain and lack of patient stratification based on diagnoses, age and treatment protocol. Moreover, data were aggregated, and we were unable to extract information from early survivorship. Conclusions: There is a critical need for more rigorous research on pain in CYP cancer survivors. Specifically, gathering data on pain experienced during the immediate post-treatment completion phase of cancer care, an area currently underrepresented in the literature, will provide valuable insights into patients’ pain trajectories. Full article

This pilot study uses Raman spectroscopy and SERS to monitor monthly water composition changes in two adjacent hypersaline lakes (L1 and L2) at a balneary resort, during the peak tourist season (May–October 2023). In situ pH and electrical conductivity (EC) measurements, along with evaporite analyses, complemented the spectroscopic data. Although traditionally considered similar, the lakes frequently raise public questions about their relative bathing benefits. While not directly addressing the therapeutic effects, the study reveals distinct physicochemical profiles between the lakes. Raman data showed consistently higher sulfate levels in L2, a trend also observed in winter monitoring. pH levels were higher in L1 (8–9.8) than in L2 (7.2–8), except for one October depth reading. This trend held during winter, except in April. Surface waters showed more variability and slightly higher values than those at 1 m depth. SERS spectra featured β-carotene peaks, linked to cyanobacteria, and Ag–Cl bands, indicating nanoparticle aggregation from inorganic ions. SERS intensity strongly correlated with pH and EC, especially in L2 (r = 0.96), suggesting stable surface–depth chemistry. L1 exhibited more monthly variability, likely due to differing biological activity. Although salinity and EC were not linearly correlated at high salt levels, both reflected seasonal trends. The integration of Raman, SERS, and physicochemical data proves effective for monitoring hypersaline lake dynamics, offering a valuable tool for environmental surveillance and therapeutic water quality assessment, in support of evidence-based water management and therapeutic use of salt lakes, aligning with goals for sustainable medical tourism and environmental stewardship. Full article

Origanum petraeum Danin, an endemic medicinal shrub from Jordan, belongs to the Lamiaceae family and possesses significant pharmaceutical potential, yet its secondary metabolite profile remains largely unexplored. This study evaluated the effects of two types of nanoparticles, silver (Ag) and copper (Cu), on in vitro propagation and secondary metabolite composition in O. petraeum microshoots. Sterilized buds were used to initiate in vitro cultures on Murashige and Skoog (MS) medium supplemented with gibberellic acid (GA₃) at 0.5 mg/L. Microshoots were treated with nanoparticles at concentrations of 0, 25, 50, 100, and 150 mg/L. AgNPs at 100 mg/L promoted growth, increasing the number of microshoots to 11.6 and shoot height to 9.22 cm. Transmission electron microscopy confirmed nanoparticle uptake and translocation, with AgNPs observed in root cells as small particles (≤24.63 nm), while CuNPs formed aggregates in leaves (47.71 nm). GC-MS analysis revealed that nanoparticles altered the volatile composition; 50 mg/L CuNPs enhanced monoterpenes, including α-terpinyl acetate (29.23%) and geranyl acetate (12.76%), whereas 50 mg/L AgNPs increased sesquiterpenes, such as caryophyllene oxide (28.45%). Control in vitro cultures without nanoparticles showed simpler profiles dominated by caryophyllene oxide, while wild plants contained both monoterpenes and sesquiterpenes, with eudesm-7(11)-en-4-ol (25.10%) as the major compound. Nutrient analysis indicated that nanoparticles influenced nutrient composition in microshoots. This study is the first to report nanoparticle-assisted growth and essential oil composition in O. petraeum, demonstrating their potential to enhance growth and secondary metabolite production for pharmacological and biotechnological applications. Full article

Neurodegeneration is intrinsically linked to aging through processes such as oxidative stress, mitochondrial dysfunction, and chronic inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) emerges as a central transcription factor regulating these molecular events and promoting cytoprotective responses. In neurodegenerative diseases, notably, frontotemporal dementia (FTD) and Parkinson’s disease (PD), genetic mutations—including MAPT, LRRK2, PINK1, PRKN, and SNCA—have been reported to alter Nrf2 signaling, both in vitro and in vivo. Melatonin, a neurohormone widely known for its strong antioxidant and mitochondria-stabilizing properties, has been shown to activate Nrf2 and restore redox balance in several experimental models of neurodegeneration. Its effects include a reduction in tau hyperphosphorylation, α-synuclein aggregation, and neuroinflammation. While most data are derived from sporadic models of Alzheimer’s disease and PD, emerging evidence supports a role for melatonin in familial forms of FTD and PD as well. Thus, targeting Nrf2 through melatonin may offer a promising approach to mitigating neurodegeneration, especially in the context of mutation-driven pathologies. Further investigation is warranted to explore mutation-specific responses and optimize the therapeutic strategies. Full article

Extracellular vesicles are critical mediators of intercellular signaling. Recent studies have revealed that, in addition to vesicular structures, smaller non-vesicular nanoparticles—termed exomeres and supermeres—also participate in intercellular communication. Detailed characterization of these nanoscale entities within biological systems is essential for elucidating their structural and functional roles. Due to their sub-50 nm dimensions, high-resolution imaging modalities such as atomic force microscopy and electron microscopy are currently the primary techniques available for their visualization. In the present study, we employed low-voltage scanning electron microscopy to investigate the size of exomeres and supermeres isolated from human blood plasma via high-speed ultracentrifugation. Platelet-poor plasma was obtained from the blood of six healthy donors (two women and four men, aged 21–46 years). By ultracentrifugation (170,000× g for 4 h), the plasma was purified of extracellular vesicles. Two fractions were sequentially isolated: one containing exomeres (170,000× g for 20 h) and one containing supermeres (370,000× g for 20 h). The particles were examined using a Zeiss Auriga microscope with no sputter coating at an accelerating voltage of 0.4–0.5 kV. The images obtained from the fractions showed particles 10–50 nm in diameter, both individual particles and aggregated structures. The fractions were also slightly contaminated with larger particles, supposedly extracellular vesicles. Examining the fractions using a dynamic light scattering device additionally revealed the presence of particles 10–18 nm in size. It should be noted that the fractions obtained did indeed contain particles measuring 10–50 nm, which corresponds to the size of exomeres and supermeres. Low-voltage scanning electron microscopy allows for examination of the structure of exomeres and supermeres in blood plasma fractions. However, it should be noted that without the use of immunological identification, this method does not allow exomeres and supermeres to be distinguished from accompanying particles. It should also be noted that because the size of exomeres and supermeres is close to the detection threshold of low-voltage scanning electron microscopy, in such studies it is generally only possible to detect the size of these particles. Full article

In the recent years, the accelerating global demographic shift toward population aging has been accompanied by a marked increase in the prevalence of neurodegenerative disorders, notably Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Among emerging approaches, dietary interventions targeting the gut–brain axis have garnered considerable attention, owing to their potential to modulate key pathogenic pathways underlying neurodegenerative processes. This review synthesizes current concepts in precision nutrition and elucidates neurohumoral, immune, and metabolic regulatory mechanisms mediated by the gut microbiota, including the roles of the vagus nerve, cytokines, short-chain fatty acids, vitamins, polyphenols, and microbial metabolites. Emerging evidence underscores that dysbiotic alterations contribute to compromised barrier integrity, the initiation and perpetuation of neuroinflammatory responses, pathological protein aggregations, and the progressive course of neurodegenerative diseases. Collectively, these insights highlight the gut microbiota as a pivotal target for the development of precision-based dietary strategies in the prevention and mitigation of neurodegenerative disorders. Particular attention is devoted to key bioactive components such as prebiotics, probiotics, psychobiotics, dietary fiber, omega-3 fatty acids, and polyphenols that critically participate in regulating the gut–brain axis. Contemporary evidence on the contribution of the gut microbiota to the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis is systematically summarized. The review further discusses the prospects of applying nutrigenomics, chrononutrition, and metagenomic analysis to the development of personalized dietary strategies. The presented findings underscore the potential of integrating precision nutrition with targeted modulation of the gut–brain axis as a multifaceted approach to reducing the risk of neurodegenerative diseases and preserving cognitive health. Full article

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, multiple sclerosis, and amyotrophic lateral sclerosis share converging mechanisms of neuronal dysfunction, including protein aggregation, oxidative stress, and chronic neuroinflammation. Glial cells, once considered passive supporters, are now recognized as central drivers of these processes, offering both pathogenic triggers and therapeutic opportunities. Yet, despite compelling preclinical evidence, the translation of glial-targeted therapies into clinical success has been limited. This review provides a critical synthesis of current knowledge by examining therapeutic strategies through the lens of their translational challenges and failures. This narrative review highlights how interspecies variability of glial phenotypes, shifting neuroprotective versus neurotoxic states, limited biomarker stratification, and delivery barriers have constrained trials, such as anti-triggering receptor expressed on myeloid cells 2 (anti-TREM2) antibodies in AD and glial cell line-derived neurotrophic factor (GDNF) in PD. By analyzing these obstacles across major neurodegenerative disorders, this review argue that the next stage of glial medicine requires precision approaches that integrate stage-specific phenotyping, biomarker-guided patient selection, and innovative delivery platforms. Understanding not only what has been tried but why translation has stalled is essential to chart a roadmap for effective, disease-modifying glial therapies in the aging brain. Full article

Objectives: This study aimed to determine the prevalence of gastrostomy-related procedures and paediatric patients undergoing these procedures, alongside temporal trends, patient profiles, and regional disparities in procedure provision. Methods: We analysed anonymised National Health Fund data pertaining to patients who underwent procedures at regional centres in Poland from 2010 to 2019. To assess temporal patterns, procedure counts and patient prevalence were aggregated annually, and trends over time were evaluated using the Mann–Kendall trend test. Results: Percutaneous Endoscopic Gastrostomy (PEG) was performed in 2638 patients, while gastrostomy-other was performed in 2087 patients. The cumulative prevalence of patients during the 10-year follow-up period was as follows: PEG: 37.7 per 100,000 children; gastrostomy—other: 29.9 per 100,000 children. The procedure prevalence rates were PEG: 40.1 per 100,000 children; gastrostomy-other: 43.0 per 100,000 children. Gastrostomy-related procedures were performed most frequently in the first three years of life. Conclusions: Patient sex, age, and centre location influenced utilization, as shown by local variations. The increasing trend in gastrostomy procedures and the young patient age indicate the growing use of gastrostomy, with endoscopic placement being the most common. Given the rising numbers requiring gastrostomy, optimizing inter-centre collaboration could contribute to the identification and treatment of patients with special nutritional needs. Full article

Despite an abundance of available research, calf mortality persists as a multifaceted phenomenon that presents ongoing challenges in practical management. This historical single-cohort study was conducted to provide a more comprehensive layer of knowledge to the existing information pool on calf mortality risk factors by using multiblock partial least squares analysis. The method reveals the contribution of several variables aggregated into thematic blocks and allows to include multiple outcome variables describing the same phenomenon. Such an analysis of the data provides valuable information to farmers, veterinarians, and advisors alike, not only about single risk factors, but also about management areas to prioritize when tackling calf mortality. Data was gathered from 118 Estonian dairy herds, each comprising ≥100 cows, via questionnaire, sample collection, and on-farm scoring and measurements. The final dataset included 147 questions divided into 13 meaningful blocks. The outcome variables were annual herd-level calf mortality risk during the first 21 days (MR21) and 22–90 days (MR90) using farm records and the national cattle database, respectively. The average MR21 was 5.9% (median 4.4%, range 0.0–26.8%) and the average MR90 was 2.7% (median 2.3%, range 0.0–12.7%). Of the 13 thematic variable blocks, the most important blocks explaining calf mortality were ‘Routine stress-inducing activities’, ‘Herd characteristics’, ‘Calving management’, ‘Calf housing during 5–21 days’, and ’External biosecurity’. The most influential single variables associated with higher overall calf on-farm mortality during the preweaning period were poorer cleanliness scores of calving animals and calves having access to an outdoor area during the first 21 days of life. Detected risk factors for MR21 were calf barn age > 20 years, allowing the calves to suckle the first colostrum, bucket feeding calves during the first three weeks, disbudding all calves (compared to only heifer calves), and disbudding at 21–29 days of age. Risk factors for MR90 included the use of automatic milk feeders and feeding waste milk during the first three weeks, early introduction of calves to large group pens and higher in-pen age differences, absence of forced ventilation during the first three weeks, opportunity for feces to spread between calf pens, and use of calving pens for sick animals. Washing and disinfection of newborn calves’ pens and testing colostrum quality were protective factors against both MR21 and MR90. Other protective practices for MR21 were related to proper colostrum feeding routines, whereas lower MR90 was mostly associated with efficient external biosecurity practices and vaccination programs. The multiblock model proved to be beneficial in providing a broader understanding of the importance of different management areas on calf mortality. Full article

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are characterized by progressive neuronal loss, driven mainly by the misfolding, aggregation, and accumulation of each disease’s specific proteins. These pathogenic aggregates, including tau, α-synuclein, TDP-43, and huntingtin, disrupt cellular proteostasis and initiate cascades of neuroinflammation, oxidative stress, mitochondrial dysfunction, and synaptic failure. While protein aggregation has been a long-recognized hallmark of these disorders, growing evidence points towards a more complex interplay of initial molecular pathways with defects in RNA processing, stress granule pathology, and cell-type-specific vulnerability. Notably, such events may manifest differentially with respect to sex and are further modulated by age-related loss of the protein quality control processes like the ubiquitin–proteasome pathway, autophagy–lysosome pathway, and molecular chaperones. This review synthesizes current insights into the structural and functional dynamics of protein aggregation and its significance for neuronal well-being. It highlights the role of post-translational modifications, prion-like transmission, and aggregation kinetics in the regulation of toxicity. The review further discusses promising therapeutic strategies centered on restoring proteostasis, including small molecules that inhibit aggregation, protein clearance pathway enhancers, immunotherapy, antioxidant therapy, and diagnostic prospects such as the identification of reliable molecular signatures in bodily fluids that can reflect pathological changes even before clinical symptoms emerge. Advancements in single-cell transcriptomics and multi-omics platforms, which are changing our understanding of disease onset and progression and opening avenues for precision medicine and personalized treatments, were also discussed. Ultimately, deciphering the molecular logic that distinguishes physiological from pathological protein assemblies and understanding how cellular systems fail to adapt under stress will be key to the development of effective, disease-modifying therapies for these debilitating disorders. Full article

Background: Systemic inflammatory indices are increasingly used to predict prognosis in colorectal cancer (CRC), yet direct comparisons between colon cancer (CC) and rectal cancer (RC) remain limited. Methods: We conducted a retrospective matched-cohort study including 296 patients (148 with CC and 148 with RC) surgically treated between January 2018 and December 2024. Patients were matched by tumor stage, sex, and age (±3 years). Preoperative blood samples were used to calculate several inflammatory markers, including Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocyte-to-Lymphocyte Ratio (MLR), Systemic Inflammation Response Index (SIRI), Systemic Immune-Inflammation Index (SII), and Aggregate Index of Systemic Inflammation (AISI). Subgroup analyses were performed based on the Charlson Comorbidity Index (>3 vs. ≤3), surgical context (elective vs. emergency), and tumor stage (T1–T2 vs. T3–T4). Results: Colon cancer patients exhibited significantly higher levels of systemic inflammation compared to those with rectal cancer, with notable differences in NLR (3.99 vs. 2.84, p < 0.001), PLR (219.8 vs. 163.3, p < 0.001), SIRI (3.7 vs. 1.91, p = 0.004), SII (1533.8 vs. 847.8, p < 0.001), and AISI (1714.7 vs. 593.6, p = 0.009). These differences remained statistically significant in key subgroups. In elective surgeries, CC patients had elevated PLR (p < 0.001), SIRI (p = 0.003), SII (p < 0.001), and AISI (p = 0.013). Among patients with advanced tumors (T3–T4), CC was associated with higher SII (p < 0.001), AISI (p = 0.008), PLR (p < 0.001), and SIRI (p = 0.004). For those with a Charlson index > 3, CC patients showed significantly higher PLR (p < 0.001), NLR (p < 0.001) and SIRI (p = 0.001). Conclusions: colon cancer presents with a markedly stronger systemic inflammatory response than rectal cancer, particularly in patients with advanced disease, elective surgical treatment, and higher comorbidity burden. These findings suggest that indices such as SIRI, SII, and PLR may serve as valuable stratification tools beyond tumor location in CRC. Full article

Tubular aggregates (TAs), ordered arrays of sarcoplasmic reticulum (SR) tubes, are the main morphological alteration found in muscle biopsies from patients affected by TA myopathy (TAM). TAM has been linked to mutations in the genes encoding for STIM1 and ORAI1, which are two proteins that mediate Store-Operated Ca²⁺ entry (SOCE). SOCE is a mechanism that allows recovery of extracellular Ca²⁺ during fatigue, when the SR becomes depleted. As TAs also form in fast-twitch muscle fibers of aging male mice (not in females), we studied the effect of sex hormones on the aggregation of TAs during aging. We administered estrogen (ad libitum in drinking water) to male mice from 10 to 18 months of age and then evaluated the following: (a) the presence of TAs using histology and electron microscopy (EM); (b) oxidative stress, a mechanism that could underlie damage to proteins and membranes (and possibly their accumulation in TAs); and (c) SOCE function during ex vivo stimulation in the presence or absence of external Ca²⁺ or SOCE blocker (BTP-2). The results collected indicate that treatment with estrogen (a) significantly reduced the formation of TAs; (b) reduced oxidative stress, which was elevated in aging male mice; and (c) restored SOCE, i.e., the capability of aged EDL muscles to use external Ca²⁺ by promoting maintenance of Ca²⁺ Entry Units (CEUs, the intracellular junctions that mediate SOCE). Finally, we also show that formation of TAs is reduced by treatment of mice with N-acetilcysteine (NAC), a potent antioxidant also administered ad libitum in drinking water. Full article

With an aging population, there is a worldwide increase in the prevalence of neurodegenerative diseases. Alzheimer’s disease (AD) is the most prevalent form of dementia. Research focusing on aging has revealed a time-related accumulation of senescent cells that escape the cell cycle but remain metabolically active and spread the senescent traits to neighboring cells via the senescence-associated secretory phenotype. The accumulated senescent cells in various tissues are involved in the pathogenesis of several age-related conditions. As such, eliminating them would be an appealing anti-aging strategy. Following the high success rates of engineered chimeric antigen receptor (CAR)-T cells in hematological malignancies, the scientific community has tried to adapt the strategy to fight aging and age-related diseases. Research in this area is only in its infancy, but the results obtained from in vitro and animal models are encouraging. Due to the serious side effects of CAR-T cell therapies (cytokine release syndrome, immune cell-associated neurological syndrome) and because in AD the elimination of neurons with neurofibrillary tangles and amyloid aggregates should be avoided (given the limited regenerative potential of these cells), CAR macrophages, CAR regulatory T cells, or exosomes derived from these cells are a more promising approach. Full article