Search Results (2,032)

Background/Objectives: Postoperative cognitive dysfunction (POCD) represents a significant and potentially preventable complication in elderly patients undergoing colorectal cancer surgery, with reported incidence ranging from 2.8% to 62.2% depending on perioperative management strategies and assessment methods. This narrative review synthesizes current evidence on the epidemiology, pathophysiology, risk factors, and prevention strategies for POCD in this vulnerable population. Methods: A comprehensive narrative review was conducted to examine the current literature on POCD in elderly colorectal cancer patients. Evidence was synthesized from published studies addressing epidemiology, assessment tools, risk factors, pathophysiological mechanisms, and prevention strategies, with a particular focus on Enhanced Recovery After Surgery (ERAS) protocols and multicomponent interventions. Results: Advanced age, pre-existing cognitive impairment, frailty, and surgical complexity emerge as key risk factors for POCD. ERAS protocols demonstrate substantial protective effects, reducing POCD incidence from 35% under conventional care to as low as 2.8% in optimized pathways. The pathophysiology involves multifactorial mechanisms, including neuroinflammation, blood–brain barrier disruption, neurotransmitter dysregulation, and oxidative stress, with surgical trauma triggering systemic inflammatory cascades that activate microglial responses within the central nervous system. Evidence-based prevention strategies include preoperative cognitive and frailty screening, minimally invasive surgical techniques, multimodal opioid-sparing analgesia, regional anesthesia, depth-of-anesthesia monitoring, and structured postoperative care bundles adapted from the Hospital Elder Life Program. Conclusions: The integration of comprehensive perioperative cognitive care protocols represents a critical priority as surgical volumes in elderly populations continue to expand globally. Emerging directions include biomarker development for early detection and risk stratification, precision medicine approaches targeting individual vulnerability profiles, and novel therapeutic interventions addressing neuroinflammatory pathways. Standardized assessment tools, multidisciplinary collaboration, and implementation of evidence-based preventive interventions offer substantial promise for preserving cognitive function and improving long-term quality of life in elderly colorectal cancer patients. Full article

Sympathetic nervous system (SNS) imbalance is a common pathological basis for cardiovascular diseases, non-alcoholic fatty liver disease, and diabetes. This review focuses on these diseases, analyzing two core mechanisms: excessive sympathetic excitation induced by endoplasmic reticulum stress (ERS) or autophagy dysfunction in key central nuclei (e.g., hypothalamus, rostral ventrolateral medulla); and ERS/autophagy abnormalities in peripheral target organs caused by chronic SNS overactivation. Existing studies confirm that chronic SNS overactivation promotes peripheral metabolic overload via sustained catecholamine release, inducing persistent ERS and disrupting the protective unfolded protein response (UPR)–autophagy network, ultimately leading to cell apoptosis, inflammation, and fibrosis. Notably, central ERS or autophagy dysfunction further perturbs autonomic homeostasis, exacerbating sympathetic overexcitation. This review systematically elaborates on SNS overactivation as a critical bridge mediating UPR–autophagy network dysregulation in central and peripheral tissues, and explores therapeutic prospects of targeting key nodes (e.g., chemical chaperones, specific UPR modulators, nanomedicine), providing a theoretical basis for basic research and clinical translation. Full article

Rapid urbanization is fragmenting ecological spaces in megacities, threatening biodiversity and ecosystem services. Yet, it remains unclear whether, and under what conditions, urban ecological networks (ENs) can recover robustness once heavily disrupted. This study aims to (i) develop a dynamic assessment framework that couples network robustness and connectivity, and (ii) apply it to examine how ENs evolve under sustained urbanization and shifting policy regimes. Using multi-period data for Shenzhen, China (2000–2025), we simulate deliberate and random attacks on patches and corridors to derive data-driven thresholds that grade the importance of ecological elements, and integrate these with graph-based connectivity metrics to track changes in network structure and node centrality over time. Shenzhen’s EN exhibits a typical “fragmentation–reconfiguration–optimization” pathway, with a “rapid decline–deceleration–recovery” trajectory in robustness that closely aligns with the introduction of strict ecological control lines and subsequent restoration initiatives. The results show that targeted protection of residual core habitats, combined with strategic reconnection and infill greening in the urban interior, can reverse earlier losses in network robustness. The proposed robustness-informed framework provides operational guidance for prioritizing protection, restoration, and optimization of ecological space, and offers a transferable approach for adaptive EN planning in high-density tropical and subtropical megacities. Full article

The blood–brain barrier and blood–spinal cord barrier (BBB/BSCB) are essential protective components for the healthy functioning of the central nervous system (CNS). While these barriers protect the CNS from peripheral factors, such as immune cells and blood products, they can become disrupted in pathological conditions and injury. The neurovascular unit (NVU) is composed of endothelial cells (ECs), pericytes, astrocytes, microglia, and neurons, all of which contribute to proper function and the maintenance of the BBB/BSCB. Tight junctions (TJs) unite cellular components and are modulated by both intrinsic and extrinsic factors. Systemic processes, such as pain (nociceptive activity), inflammation, and blood hemostasis, can impact BBB/BSCB function, often leading to a disrupted barrier and increased peripheral infiltration. This, in turn, can increase neuroinflammation and drive microglia activation, progressive hemorrhagic necrosis (PHN), and matrix metalloproteinase (MMP) activity. Targeting these processes and mitigating the deleterious effects of BBB/BSCB breakdown represents a key therapeutic target after neural injury and other pathological conditions. Full article

Background/Objectives: Cerebral angiography is a cornerstone diagnostic and therapeutic procedure for cerebrovascular diseases; however, its potential effects on vascular integrity and cellular homeostasis remain incompletely elucidated. This systematic review aims to comprehensively evaluate endothelial and histopathological alterations induced by cerebral angiographic procedures, with particular emphasis on oxidative stress, inflammation, endothelial dysfunction, and blood–brain barrier disruption. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science databases were systematically searched for studies published between 1981 and 2025 using predefined keywords related to cerebral angiography, endothelial injury, oxidative stress, inflammation, and histopathological changes. A total of 1142 records were identified, and 216 duplicates were removed. Following title and abstract screening, 312 full-text articles were assessed for eligibility, of which 112 were excluded due to irrelevance or insufficient endothelial or histopathological data. Ultimately, 200 studies were included in the qualitative synthesis. The literature identification, screening, and selection process are summarized in the manuscript. The review protocol was not prospectively registered. Results: The included studies demonstrated that cerebral angiographic procedures induce endothelial and microvascular alterations through both mechanical and contrast-mediated mechanisms. Iodinated contrast agents were consistently associated with increased reactive oxygen species production, reduced endothelial nitric oxide bioavailability, mitochondrial dysfunction, and activation of pro-inflammatory signaling pathways, including nuclear factor kappa B (NF-κB). Histopathological findings revealed endothelial swelling, vacuolization, apoptosis, microthrombus formation, inflammatory cell infiltration, and disruption of endothelial junctions, leading to increased vascular permeability and blood–brain barrier impairment. Mechanical factors related to catheter manipulation and high-pressure contrast injection further exacerbated endothelial injury by altering shear stress and promoting leukocyte adhesion. The severity of endothelial damage and inflammatory responses was consistently greater in patients with comorbid conditions such as diabetes mellitus, hypertension, and atherosclerotic disease. Conclusions: Cerebral angiography may induce endothelial dysfunction and histopathological vascular injury predominantly through oxidative and inflammatory mechanisms. Optimization of contrast agent selection, refinement of procedural techniques, and implementation of endothelial-protective strategies may mitigate vascular injury and improve procedural safety. Further translational and clinical studies are warranted to identify biomarkers and protective interventions targeting angiography-induced endothelial damage. Full article

Trimeric intracellular cation channel A (TRIC-A) provides counter-ion support for sarcoplasmic reticulum (SR) Ca²⁺ release, yet its physiological role in the intact heart under stress remains poorly defined. Here, we demonstrate that TRIC-A is essential for maintaining balanced SR Ca²⁺ release, mitochondrial integrity, and cardiac resilience during β-adrenergic stimulation. Tric-a^−/− cardiomyocytes exhibited Ca²⁺ transients evoked by electrical stimuli and exaggerated isoproterenol (ISO)-evoked Ca²⁺ release, consistent with SR Ca²⁺ overload. These defects were accompanied by selective upregulation of protein kinase A (PKA)-dependent phosphorylation of ryanodine receptor 2 (RyR2) (S2808) and phospholamban (PLB) (S16). Acute ISO challenge induced mitochondrial swelling, cristae disruption, and Evans Blue Dye uptake, and elevated circulating troponin T in Tric-a^−/− hearts, hallmarks of necrosis-like cell death. Mitochondrial Ca²⁺ uptake inhibition with Ru360 markedly reduced membrane injury, establishing mitochondrial Ca²⁺ overload as the proximal trigger of cardiac cell death. With sustained β-adrenergic stimulation by ISO, Tric-a^−/− hearts developed extensive interstitial and perivascular fibrosis without exaggerated hypertrophy. Cardiac fibroblasts lacked TRIC-A expression and displayed normal Ca²⁺ signaling and activation, indicating that fibrosis arises secondarily from cardiomyocyte injury rather than fibroblast-intrinsic abnormalities. These findings identify TRIC-A as a critical regulator of SR-mitochondrial Ca²⁺ coupling and a key molecular safeguard that protects the heart from catecholamine-induced injury and maladaptive remodeling. Full article

Oxidative stress is a major factor in skin aging and various skin pathologies. Environmental pollutants exacerbate this stress by generating reactive oxygen species (ROS), disrupting the skin’s redox balance. Pycnogenol^®, a French maritime pine bark, extract is standardized to contain 70 ± 5% procyanidins and known to mitigate oxidative damage and inflammation. This study aims to evaluate the potential antipollution and antioxidant effects of Pycnogenol^® on skin. Ex vivo human skin explants were treated with varying concentrations of Pycnogenol^® (0.5%, 1%, and 2%) and then exposed to a mixture of pollutants. The expression of stress markers Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) and AHR (Aryl Hydrocarbon Receptor) were evaluated using immunostaining. Lipid peroxidation levels were measured by quantifying malondialdehyde (MDA) concentrations. The extract significantly decreased Nrf2 expression by 40% (p = 0.003) and 23% (p = 0.048) with a dose of 2% and 1%, respectively. After pollutant exposure, Pycnogenol^® (0.5%, 1%, and 2%) reduced Nrf2 over-expression in a dose–response manner by 29% (p = 0.03), 58% (p = 0.004) and 64% (p = 0.002) respectively. Pycnogenol^® at 0.5%, 1%, and 2% significantly reduced AHR over-expression by 61% (p < 0.0001), 76% (p < 0.0001) and 85% (p < 0.0001), respectively. Pycnogenol^® (1%, and 2%) decreased MDA levels following pollutant exposure by 17% (p = 0.06) and 25% (p = 0.01) respectively. In a dose-dependent manner, Pycnogenol^® exhibited a strong protective effect against pollution, significantly reducing pollutant-induced basal oxidative stress (MDA) and over-expression of Nrf2 and AHR, key factors in oxidative stress and detoxification. Pycnogenol^® also increased AHR expression in the absence of pollutants, which may reflect an adaptive cellular response. Full article

Drought stress is a major abiotic factor limiting global crop productivity by disrupting cellular homeostasis, impairing photosynthesis, and restricting metabolic activity. Plant-associated microorganisms, including rhizobacteria, endophytes, and arbuscular mycorrhizal fungi, play key roles in enhancing drought resilience through molecular, biochemical, and physiological mechanisms. These beneficial microbes modulate phytohormone biosynthesis, enhance osmolyte accumulation, increase organic acid exudation, and activate ROS-scavenging antioxidant pathways. Microbe-mediated regulation of aquaporins, heat shock proteins, and root system architecture further improves water-use efficiency, hydraulic conductance, and stress acclimation. Advances in microbial genomics and systems biology have revealed the molecular drivers of plant–microbe synergism, enabling the development of tailored microbial consortia and next-generation bioinoculants. Complementarily, genetic and genome-guided modulation of drought-responsive regulatory hubs including transcription factors (DREB, NAC, MYB, bZIP), signal transducers (MAPKs, CDPKs), and protective proteins enhances adaptive plasticity under water deficit conditions. This review integrates current molecular insights into drought-induced perturbations in plants and highlights the convergence of microbial interventions and genome-guided strategies in reinforcing drought tolerance. Emphasizing mechanistic frameworks, scalable microbial technologies, and molecular breeding approaches, this work underscores their potential to improve crop resilience in increasingly water-limited environments. Full article

Laryngopharyngeal reflux disease (LPRD) results from the retrograde flow of gastric contents into the upper aerodigestive tract, causing epithelial injury. Progress in its management has been limited by the lack of objective biomarkers and reproducible in vivo models. This study aimed to establish a chronic, non-surgical mouse model of LPRD and to investigate the protective effect of N-acetylcysteine (NAC). Female C57BL/6 mice were randomly assigned to three groups: control (standard drinking water), study (acidified water, pH 3.0, for 12 weeks), and treatment (acidified water for 12 weeks plus NAC supplementation during the final 4 weeks). Body weight, food intake, and water consumption were monitored weekly. Pharyngeal tissues were analyzed by immunohistochemistry and Western blotting. Chronic acid exposure resulted in loss of membrane-localized E-cadherin, cytoplasmic redistribution, and upregulation of matrix metalloproteinase-7 (MMP-7). These molecular alterations were accompanied by enhanced phosphorylation of ERK and c-Jun, consistent with activation of the ROS–ERK–c-Jun signaling pathway. NAC supplementation was associated with partial restoration of E-cadherin, reduced MMP-7 expression, and attenuation of ERK/c-Jun phosphorylation. No systemic toxicity or weight loss was observed, indicating good tolerability of the model. This non-surgical ingestion-based model faithfully recapitulates key epithelial features of LPRD and provides a feasible platform for mechanistic investigation and exploratory therapeutic studies. NAC may exert protective effects against acid-induced epithelial injury in this model. Full article

Doxorubicin (DOX), a widely used chemotherapeutic, is constrained by its nephrotoxicity, characterized by endothelial injury, inflammation, and oxidative stress. Vascular endothelial growth factor (VEGF) signaling in the kidney serves a dual function. Under normal conditions, it supports the survival of glomerular endothelial cells and maintains vascular stability, but when excessively activated, it disrupts angiogenesis and contributes to kidney injury. In this context, we hypothesize that Nanocurcumin (CUR-NP), a nano-formulated curcumin derivative with enhanced bioavailability, can modulate the VEGF pathway and restore regular renal activity. Thus, this study aims to explore the potential protective effect of CUR-NP on DOX-induced renal injury in male rats. Thirty-two Wistar albino rats were used and distributed into four groups. CUR-NP (80 mg/kg dissolved in 1% CMC) was administered by oral gavage for two weeks. A single dose of DOX (15 mg/kg) (i.p.) was injected on day seven of the study. Results showed that DOX increased the circulating creatinine, urea, and urea-nitrogen levels, while pretreatment with CUR-NP markedly alleviated kidney function. In addition, CUR-NP treatment significantly normalized oxidative stress markers in renal tissues, such as NO, GSH, and SOD, and improved renal pro-inflammatory mediators, TNF-α, IL-6, and NF-κB-p65. DOX caused degeneration of glomeruli and tubules with degenerated epithelial lining and casts in their lumens. Conversely, CUR-NP maintained standard tubular and glomerular structure. Immunohistochemistry showed that DOX strongly upregulated VEGF and AhR, while CUR-NP markedly reduced their expression, countering VEGF/AhR pathway disruption and helping restore physiological signaling. Full article

In achieving sustainable development goals, soils play a key role in environmental protection, natural resources, and food security. Peatlands are particularly important here, as they function at the interface between terrestrial and aquatic ecosystems and store large amounts of organic matter. However, organic soils are highly susceptible to transformation and degradation; therefore, their degradation caused by, among others, drainage properties is a high risk to both the environment and agriculture—it disrupts the ecosystems, causes greenhouse gas emissions, and eutrophicates the hydrosphere. Soil degradation in drained peatlands is associated with the transformation of soil organic matter (SOM), which in organic soils is the dominant component of the solid phase of the soil. The aim of our study was to assess the properties and degree of organic matter transformation in drained temperate peatland soils, with particular emphasis on sequential fractionation of SOM and humic acid properties. Due to the fact that in Poland, as many as 90% of non-forest peat bogs have been drained, we compare the mursh horizons that formed after peat bog drainage with the peat horizons that constitute the parent rock (where anaerobiosis occurs and morphological changes in the soil material are absent due to peat bog drainage). Studies were conducted on 11 soil profiles located in central-eastern Poland. Basic physicochemical soil properties were determined: pH, bulk density, contents of ash, SOM, total carbon (TC), and total nitrogen (TN). Sequential carbon fractionation was used to qualitatively analyze organic matter, which allowed for the identification of labile fractions, lipid fractions, humic substances (fulvic and humic acids), and residual fractions. Humic acids (HAs) were extracted using the Schnitzer method and analyzed for their elemental composition and spectrometric parameters in the VIS range. It was demonstrated that SOM transformation in drained temperate peatland soils was correlated with comprehensive changes in the soil’s physical and chemical properties. Compared to peat horizons, topsoil horizons were characterized by higher ash content and density, lower SOM content, and a lower TC/TN ratio. Qualitative SOM transformation during aerobic SOM transformation after draining the studied peatlands consisted of an increase in the amount of labile fractions and humic substances and a decrease in the lipid and residual fractions. The research results have shown that the HAs properties depended on the depth. HAs from topsoil horizons, compared to peat horizons, were characterized by a lower “degree of maturity,” as reflected by the values of atomic ratios (H/C, O/C) and absorbance coefficients (A_4/6 and ΔlogK). It was found that the share of the distinguished SOM fractions and HAs properties were closely correlated with the physical and chemical properties of the soils. The study demonstrated the usefulness of the sequential carbon fractionation method for assessing the effects of dewatered peat transformation. The obtained results could contribute to the development of good practices ensuring high quality of organic matter and stability of ecosystems, as well as to the development of methods for limiting the mineralization of organic matter (SOM), greenhouse gas emissions, and the loss of organic soils in agricultural areas. Full article

Cells are continuously exposed to physiological and environmental stressors that disrupt homeostasis, triggering adaptive mechanisms such as the integrated stress response (ISR). A central feature of ISR is the selective translation of activating transcription factor 4 (ATF4), which orchestrates gene programs essential for metabolic adaptation and survival. Stress-induced acute ATF4 expression occurs in diverse mammalian cell types and is typically protective; however, chronic activation contributes to pathologies including cancer and neurodegeneration. Canonical ISR (c-ISR) is initiated by phosphorylation of eIF2α in response to stressors such as endoplasmic reticulum or mitochondrial dysfunction, hypoxia, nutrient deprivation, and infections. This modification suppresses global protein synthesis while promoting ATF4 translation through upstream open reading frames (uORFs) in its 5′UTR. Recently, an alternative pathway, split ISR (s-ISR), enabling ATF4 translation independently of eIF2α phosphorylation, was identified in mice, suggesting ISR adaptability, though its relevance in humans remains unclear. Under normal conditions, cap-dependent translation predominates, mediated by the eIF4F complex and requiring the activity of eIF2B at its initial steps. During translational stress, eIF2α phosphorylation inhibits eIF2B activity, resulting in the formation of stalled initiation complexes, which can aggregate into stress granules (SGs). SGs sequester mRNAs and translation initiation factors, further repressing global translation, while ATF4 mRNA largely escapes sequestration, enabling selective translation. This partitioning highlights a finely tuned regulatory mechanism balancing ATF4 expression during stress. Recent advances reveal that, beyond cis-regulatory uORFs, trans-acting factors such as translation initiation factors and associated RNA-binding proteins critically influence ATF4 translation. Understanding these mechanisms provides insight into ISR plasticity and its implications for development, aging, and disease. Full article

Blockchain is widely promoted as a tool for enhancing transparency, trust, and sustainability in business, yet little is known about how creative micro, small, and medium enterprises (MSMEs) in emerging economies can meaningfully adopt it for finance and accounting purposes in times of global uncertainty. This study explores how blockchain can be harnessed for transparent and sustainable accounting in Indonesian creative MSMEs amid rapid digital disruption. Using an exploratory qualitative design, we conducted semi-structured, in-depth interviews with 18 owners and key decision-makers across diverse creative subsectors and analysed the data thematically through an integrated Technology Acceptance Model (TAM) and Diffusion of Innovation (DOI) lens. The findings show that participants recognise blockchain’s potential benefits for transaction transparency, verifiable records, intellectual property protection, and secure payments, but adoption is constrained by technical complexity, financial constraints, limited digital and accounting capabilities, and perceived regulatory and reputational risks. Government initiatives are seen as important for legitimacy yet insufficient without concrete guidance, capacity-building, and financial support. The study extends TAM–DOI applications to blockchain-enabled accounting in creative MSMEs and highlights the need for sequenced, ecosystem-based interventions to translate blockchain’s technical promise into accessible, ESG- and SDG-oriented accounting solutions in the creative economy. Full article

The functional deterioration of granulosa cells (GCs), essential for follicular growth, steroidogenesis, and oocyte competence, indicates ovarian aging and reduced fertility. An expanding corpus of research indicates that oxidative stress is a primary molecular contributor to granulosa cell dysfunction, culminating in mitochondrial impairment, reduced metabolic support for oocytes, and the activation of regulated apoptotic pathways that end in follicular atresia. Ferroptosis, an emergent type of iron-dependent lipid peroxidation, has been identified as a crucial mechanism contributing to chemotherapy-induced ovarian insufficiency, polycystic ovary syndrome (PCOS), and granulosa cell death in aging ovaries, in addition to conventional apoptosis. The SIRT1-Nrf2 axis acts as a crucial anti-oxidative and anti-ferroptotic system that protects GC viability, maintains mitochondrial homeostasis, and upholds redox equilibrium. SIRT1 promotes mitochondrial biogenesis and metabolic resilience by deacetylating downstream proteins, including FOXO3 and PGC-1α. Nrf2 simultaneously controls the transcriptional activation of detoxifying and antioxidant enzymes, including HO-1, SOD2, NQO1, and GPX4, which are critical inhibitors of ferroptosis. Disruption of SIRT1-Nrf2 signalling accelerates GC senescence, follicular depletion, and reproductive aging. In contrast, pharmaceutical and nutraceutical therapies, including metformin, melatonin, resveratrol, and agents that increase NAD⁺ levels, may reverse ovarian deterioration and reactivate SIRT1-Nrf2 activity. This narrative review highlights innovative treatment prospects for ovarian aging, fertility preservation, and assisted reproduction by synthesising current evidence on ferroptotic pathways, SIRT1-Nrf2 interactions, and oxidative stress in granulosa cells. An understanding of these interrelated biological networks enables the development of tailored therapies that postpone ovarian ageing and enhance reproductive outcomes for women receiving fertility therapy. Full article

Kidney cells are exposed to a wide range of physiological and pathological stresses, including hormonal changes, mechanical forces, hypoxia, hyperglycemia, and inflammation. These insults can trigger adaptive responses, but when they persist, they can lead to organelle stress. Organelles such as mitochondria, the endoplasmic reticulum, and primary cilia sustain cellular metabolism and tissue homeostasis. When organelle stress occurs, it disrupts cellular processes and organelle communication, leading to metabolic dysfunction, inflammation, fibrosis, and progression of kidney disease. Sex and hormonal factors play a significant role in the development of renal disorders. Many glomerular diseases show distinct differences between the sexes. Chronic Kidney Disease is more common in women, while men often experience a faster decline in kidney function, partly due to the influence of androgens. Additionally, the loss of female hormonal protection after menopause highlights the importance of sex as a factor in renal susceptibility. This narrative review synthesizes preclinical evidence on how sexual dimorphism and sex hormones affect organelle stress in mitochondria, the endoplasmic reticulum, and primary cilia, from 33 studies identified through a non-systematic literature search of the PubMed database, to provide an overview of how these mechanisms contribute to sex-specific differences in kidney disease pathophysiology. Full article