Search Results (530)

Diabetic foot complications represent a major global health burden and arise from a multifactorial interaction between neuropathy, ischemia, infection, and impaired wound repair. Increasing evidence suggests that, beyond traditional vascular and metabolic risk factors, endocrine dysregulation plays a central role in shaping vascular dysfunction and tissue vulnerability in patients with diabetes. This narrative review provides an updated overview of the endocrine–vascular axis in the development, progression, and healing of diabetic foot ulcers (DFUs), integrating evidence from experimental and clinical studies identified through targeted searches of PubMed, Embase, and Scopus. We examine how alterations in insulin signaling, relative glucagon excess, adipokine imbalance, dysregulation of stress hormones, and thyroid dysfunction interact with chronic hyperglycemia, dyslipidemia, mitochondrial dysfunction, and low-grade inflammation to impair endothelial homeostasis. These disturbances promote oxidative stress, reduce nitric oxide bioavailability, and compromise microvascular perfusion, thereby creating a pro-ischemic and pro-inflammatory tissue environment that limits angiogenesis, extracellular matrix (ECM) remodeling, immune coordination, and effective wound repair. By linking pathophysiological mechanisms to clinical relevance, this review highlights potential biomarkers of endocrine–vascular dysfunction, implications for risk stratification, and emerging therapeutic perspectives targeting metabolic optimization, endothelial protection, and hormonal modulation. Finally, key knowledge gaps and priority areas for future translational and clinical research are discussed, supporting the development of integrated endocrine-based strategies aimed at improving DFU prevention, healing outcomes, and long-term limb preservation in patients with diabetes. Full article

Sustained abiotic stress severely impairs fruit crop growth and development. As plants’ primary environmental sensing organ, fruit tree roots experience disrupted morphogenesis and physiological functions, reducing yield, lowering fruit quality, and threatening orchard ecosystem stability. Abiotic stress is diverse: water deficit from drought, extreme temperature fluctuations, and salinization-induced ion imbalance, heavy metal accumulation, or nutrient disorders. Its complexity requires synergistic and crosstalk regulation of multiple root-specific signaling modules and pathways in root stress perception and transduction. When responding to stress, roots activate hormone, reactive oxygen species (ROS), and calcium ion (Ca²⁺) signaling. These pathways mediate early stress recognition and regulate downstream gene expression and physiological metabolic reprogramming via transcription factors (TFs) and other regulators, determining stress tolerance and adaptability. Using typical abiotic stresses as models, this review outlines the composition, activation mechanisms, specificity, and synergistic effects of root-specific signaling modules/pathways, along with modern biotechnologies for decoding these modules and current research limitations, aiming to reveal the root signal network’s integration mode. Full article

Hollowness of the cucumber fruit, caused by carpel separation during growth, severely impacts fruit quality. Several Sikkim cucumber accessions originating from the India–Pakistan region exhibit pronounced internal cavities. We previously identified the QTL mfh2.1 as a key contributor to this phenotype. In this study, we investigated the genetic and physiological basis of fruit hollowness in the Sikkim cucumber line WI7120 through an integrative analysis combining histological staining, HPLC for hormonal profiling, and fine mapping using a large F2 segregation population. Comparative analysis between the hollow-fruited WI7120 and the non-hollow line 9930 revealed distinct growth dynamics: WI7120 displayed accelerated radial expansion and aberrant cell patterning at carpel junctions. Histological examination using paraffin sectioning uncovered disorganized endocarp cell arrangements in WI7120 occurring as early as pre-anthesis (0 days post-pollination), with enlarged suture cells that likely facilitate tissue separation during fruit enlargement. Hormonal assays indicated elevated levels of gibberellin (GA) and zeatin (ZT), along with reduced indole-butyric acid (IBA) in WI7120, suggesting that a hormonal imbalance and mechanical stress contribute to compromised cell adhesion. By screening ~2000 F₂ individuals with SSR and InDel markers, we refined the mfh2.1 locus to a 50.92 kb interval on chromosome 2, pinpointing CsRPT4Bb—encoding a 26S proteasome subunit—as the candidate gene. A non-synonymous SNP (I135V) in CsRPT4Bb was associated with tissue-specific expression patterns during cavity formation, implicating proteasome-mediated cellular remodeling in carpel cohesion. Spatial-temporal expression analysis further revealed upregulation of CsRPT4Bb in the WI7120 exocarp during fruit expansion, potentially influencing cell wall dynamics. This study demonstrates a coordinated interplay among genetic, hormonal, and mechanical factors underlying cucumber fruit hollowness, offering new avenues for breeding cultivars with improved fruit integrity and postharvest quality. Full article

Agriculture faces increasing challenges in ensuring food security under a changing climate, where abiotic stresses such as salinity and drought represent major constraints to crop productivity. These stresses induce complex physiological and biochemical alterations in plants, including osmotic imbalance, oxidative damage, and disruption of metabolic pathways, ultimately impairing growth and yield. In this context, the application of biostimulants has emerged as a sustainable strategy to enhance plant resilience. While synthetic products are widely available, growing attention is being directed toward natural bio-based products, particularly those derived from renewable biomasses and organic wastes, in line with circular economy principles. This review critically examines the current literature on bio-based products with biostimulant properties, with particular emphasis on vermicompost-derived extracts, humic-like substances, and macro- and microalgae extracts, focusing on their role in mitigating salt and drought stress in plants. The reviewed studies consistently demonstrate that these bio-products enhance plant tolerance to abiotic stress by modulating key physiological and biochemical processes, including hormonal regulation, activation of antioxidant defence systems, accumulation of osmoprotectants, and regulation of secondary metabolism. Moreover, evidence indicates that these bio-based inputs can improve nutrient use efficiency, photosynthetic performance, and overall plant growth under stress conditions. Overall, this review highlights the potential of non-microbial bio-based biostimulants as effective and sustainable tools for climate-resilient agriculture, while also underlining the need for further research to standardize formulations, clarify mechanisms of action, and validate their performance under field conditions. Full article

Women exhibit a higher prevalence of depression, anxiety, stress-related disorders, and autoimmune conditions compared to men, yet the biological mechanisms underlying this sex difference remain incompletely understood. Growing evidence identifies neuroinflammation as a central mediator of psychiatric vulnerability in women, shaped by interactions between sex hormones, immune activation, and neural circuit regulation. Throughout the female lifespan, fluctuations in estrogen and progesterone, such as those occurring during puberty, the menstrual cycle, pregnancy, postpartum, and perimenopause, modulate microglial activity, cytokine release, and neuroimmune signaling. These hormonal transitions create windows of heightened sensitivity in key brain regions involved in affect regulation, including the amygdala, hippocampus, and prefrontal cortex. Parallel variations in systemic inflammation, mitochondrial function, and hypothalamic–pituitary–adrenal (HPA) axis responsivity amplify stress reactivity and autonomic imbalance, contributing to increased risk for mood and anxiety disorders in women. Emerging data also highlight sex-specific interactions between the immune system and monoaminergic neurotransmission, gut–brain pathways, endothelial function, and neuroplasticity. This review synthesizes current neuroscientific evidence on the sex-dependent neuroinflammatory mechanisms that bridge hormonal dynamics, brain function, and psychiatric outcomes in women. We identify critical periods of vulnerability, summarize converging molecular pathways, and discuss novel therapeutic targets including anti-inflammatory strategies, estrogen-modulating treatments, lifestyle interventions, and biomarkers for personalized psychiatry. Understanding neuroinflammation as a sex-specific process offers a transformative perspective for improving diagnosis, prevention, and treatment of psychiatric disorders in women. Full article

Low back pain (LBP) represents a major societal and economic burden, with annual costs in the United States estimated at $90–134.5 billion. LBP disproportionately impacts postmenopausal women relative to age-matched men, suggesting a role for sex-specific biological factors. Although the mechanisms underlying this disparity are not fully understood, hormonal imbalance during menopause may contribute to LBP pathophysiology. This narrative review aimed to elucidate the impact of menopause on LBP, with emphasis on hormonal effects on spinal tissues and systemic processes. A literature search was conducted, followed by screening of titles, abstracts, and full texts of original clinical studies, preclinical research using human or animal samples, and relevant reviews. Rigour and reproducibility were evaluated using the ARRIVE Guidelines and the Modified Downs & Black Checklist. Evidence indicates that menopause is associated with changes in intervertebral discs, facet joint, ligamentum flavum, skeletal muscle, sympathetic innervation, and systemic systems such as the gut microbiome. However, most findings are correlational rather than causal. Evidence supporting hormone replacement therapy for LBP remains inconclusive, whereas exercise and other treatments, including parathyroid hormones, show more consistent benefits. Future studies should focus on causal mechanisms and adhere to rigour guidelines to improve translational potential. Full article

Primary hypoadrenocorticism (Addison’s disease) is an uncommon but potentially life-threatening endocrine disorder in dogs. Affected animals may present with clinicopathological features mimicking acute kidney injury (AKI). The challenge in diagnosing hypoadrenocorticism arises from its highly heterogeneous and non-specific clinical presentation, including acute kidney injury (AKI). This retrospective observational study aimed to evaluate dogs presenting with AKI and to identify cases in which primary hypoadrenocorticism was the underlying etiology. Thirty-four dogs diagnosed with acute kidney injury were evaluated at the Clinical Hospital for Companion Animals of the “Ion Ionescu de la Brad” University of Life Sciences, Iași, Romania, among which three (8.8%) were endocrinologically confirmed to have primary hypoadrenocorticism. The evaluation protocol included a complete clinical examination, hematological, biochemical, and hormonal investigations, urinalysis, abdominal ultrasonography, and an ACTH stimulation test. These dogs exhibited hyponatremia, hyperkalemia, a reduced sodium-to-potassium ratio, and azotemia at admission, closely resembling intrinsic AKI. Following fluid therapy and hormone replacement, rapid normalization of electrolyte and renal parameters was observed. These findings support hypovolemia and electrolyte imbalance as the primary mechanisms underlying reversible prerenal azotemia in these cases. If not diagnosed early, this condition has a significant risk of progressing to acute tubular necrosis. The findings highlight the need for careful differentiation between primary AKI and renal dysfunction secondary to Addison’s disease, as well as the importance of promptly initiating hormone replacement therapy. In conclusion, hypoadrenocorticism should be considered in dogs presenting with AKI and electrolyte imbalance. Early endocrine evaluation and prompt initiation of targeted therapy are essential to avoiding misdiagnosis and optimizing clinical outcomes. Full article

Obesity has reached epidemic proportions, driven by energy imbalance and limited capacity for adaptive thermogenesis. Brown (BAT) and beige adipose tissues dissipate energy through non-shivering thermogenesis (NST), primarily via uncoupling protein-1 (UCP1), making them attractive targets for increasing energy expenditure (EE). The canonical β-adrenergic pathway robustly activates NST in rodents through β3 adrenoceptors; however, translational success in humans has been limited by low β3 expression, off-target cardiovascular effects, and the emerging dominance of β2-mediated signaling in human BAT. Consequently, attention has shifted to non-adrenergic and UCP1-independent mechanisms that offer greater tissue distribution and improved safety profiles. This review examines a broad spectrum of alternative receptors and pathways—including GPRs, TRP channels, TGR5, GLP-1R, thyroid hormone receptors, estrogen receptors, growth hormone, BMPs, sirtuins, PPARs, and interleukin signaling—as well as futile substrate cycles (Ca²⁺, creatine, and glycerol-3-phosphate) that sustain thermogenesis in beige adipocytes and skeletal muscle. Pharmacological agents (natural compounds, peptides, and small molecules) and non-pharmacological interventions (cold exposure, exercise, diet, and time shift) targeting these pathways are critically evaluated. We highlight the translational gaps between rodent and human studies, the promise of multimodal therapies combining low-dose adrenergic agents with non-adrenergic activators, and emerging strategies such as sarco/endoplasmic reticulum calcium ATPase protein (SERCA) modulators and tissue-specific delivery. Ultimately, integrating adrenergic and non-adrenergic approaches holds the greatest potential for safe, effective, and sustainable obesity management. Full article

Motor disorders are increasingly recognized as a significant complication of chronic kidney disease (CKD), yet they remain underdiagnosed, undertreated, and often overlooked in clinical practice. Patients with CKD experience a broad spectrum of motor disturbances, including restless legs syndrome, myoclonus, flapping tremor, periodic limb movements in sleep, Parkinsonism, and peripheral neuropathy. These disorders arise from complex and often overlapping mechanisms such as uremic neurotoxicity, vascular injury, electrolyte and hormonal imbalances, or inflammatory processes, reflecting the systemic impact of impaired renal function on the central and peripheral nervous systems. The presence of motor disorders in CKD is associated with substantial clinical consequences for quality of life, contributing to impaired mobility, persistent insomnia, daytime fatigue, higher fall risk, and diminished independence. Moreover, these disturbances have been linked to increased cardiovascular morbidity and mortality, further exacerbating the already high burden of disease in this population. Current management approaches focus on optimizing kidney function through dialysis or transplantation, pharmacological therapies such as dopaminergic agents, gabapentinoids, and iron supplementation, as well as non-pharmacological interventions including structured exercise programs and sleep hygiene measures. Despite these strategies, robust evidence on long-term outcomes, comparative effectiveness, and optimal treatment algorithms remains limited. Greater recognition of the clinical impact of motor disorders in CKD, combined with targeted research efforts, is urgently needed to improve patient-centered outcomes and guide evidence-based care. Full article

Background: Growing evidence indicates that oral microbiome dysbiosis contributes to systemic inflammation, immune activation, and neural dysfunction. These processes may influence the onset and progression of major neuropsychiatric and neurodegenerative disorders. This review integrates clinical, epidemiological, and mechanistic findings linking periodontal pathogens and oral microbial imbalance to Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, and anxiety. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify recent studies examining alterations in the oral microbiota, microbial translocation, systemic inflammatory responses, blood–brain barrier disruption, cytokine signaling, and neural pathways implicated in brain disorders. Results: Evidence from human and experimental models demonstrates that oral pathogens, particularly Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, can disseminate systemically, alter immune tone, and affect neural tissues. Their virulence factors promote microglial activation, cytokine release (IL-1β, IL-6, TNF-α), amyloid-β aggregation, and α-synuclein misfolding. Epidemiological studies show associations between oral dysbiosis and cognitive impairment, motor symptoms in PD, and alterations in mood-related taxa linked to stress hormone profiles. Immunometabolic pathways, HPA-axis activation, and the oral–gut–brain axis further integrate these findings into a shared neuroinflammatory framework. Conclusions: Oral dysbiosis emerges as a modifiable contributor to neuroinflammation and brain health. Periodontal therapy, probiotics, prebiotics, synbiotics, and targeted inhibitors of bacterial virulence factors represent promising strategies to reduce systemic and neural inflammation. Longitudinal human studies and standardized microbiome methodologies are still needed to clarify causality and evaluate whether restoring oral microbial balance can modify the course of neuropsychiatric and neurodegenerative disorders. Full article

Background. The aim of this study was to develop a predictive model of anticancer drug therapy toxicity in patients with gastric cancer. Methods. The retrospective study included 100 patients with stage II–IV gastric cancer who underwent 4 chemotherapy cycles. Initial significant toxicity factors included age, gender, height, body mass, body mass index, disease stage, skeletal muscle index (SMI), as well as plasma levels of trace elements (copper, zinc, selenium, manganese) and thyroid-stimulating hormone, cancer histology type and treatment regimen. The CTCAE v5.0 scale was employed to assess the severity of adverse events. Statistical analysis and building of mathematical neural network models were carried out in SPSS Statistics (v19.0). Results. Lower SMI values were associated with higher rates of toxicity-related complications of anticancer drug therapy (p < 0.05): leukopenia, hypoproteinemia, nausea, vomiting, cardiovascular events. Anemia, thrombocytopenia, hepatic cytolysis syndrome, nausea, diarrhea, constipation and stomatitis showed a weaker correlation with SMI. An increase in TSH was associated with higher rates of thrombocytopenia, nausea and vomiting. A decrease in Cu/Zn in plasma correlated with the severity of leukopenia and diarrhea, whereas Se/Mn showed an inverse correlation with the severity of anemia. Conclusions. Sarcopenia, abnormal thyroid status and imbalances in copper, zinc, selenium and manganese in blood plasma of patients with gastric cancer may be used as predictors of increased toxicity of anticancer drug therapy. Full article

Phosphorus (P) is a key macromineral essential for numerous physiological processes, including energy metabolism, skeletal mineralization, and cellular signaling. In dairy cattle, its homeostasis is tightly regulated by parathyroid hormone, calcitriol, and fibroblast growth factor 23 (FGF23). Phosphorus deficiency is common during the transition period and is associated with reduced milk yield, anemia, muscle weakness, and immunosuppression in severe or prolonged cases. This review summarizes the current understanding of phosphorus metabolism in ruminants, emphasizing differences from monogastric species, hormonal regulation, and the clinical manifestations of deficiency. Particular attention is given to postpartum hypophosphatemia, its relationship with acute-phase proteins, and the pathogenesis of postpartum hemoglobinuria and recumbency. The review also discusses diagnostic methods for assessing phosphorus status, recent findings on FGF23 physiology in cattle, and including demonstrated effects of phosphorus imbalance on periparturient immune suppression and increased environmental phosphorus losses through manure. Maintaining optimal phosphorus nutrition is crucial for bovine health, productivity, and reduction in environmental phosphorus losses. Full article

Microplastics (MPs) and nanoplastics (NPs) are widespread environmental contaminants with documented impacts on human health, particularly on the female reproductive system. Defined as polymeric fragments smaller than 5 mm, MPs (typically ranging from 1 µm to 5 mm) and NPs (smaller than 1 µm, often <100 nm) originate either from primary sources—intentionally manufactured for specific industrial applications—or from secondary sources through physical, chemical, or biological degradation of macroplastics. Human exposure occurs via multiple routes, including ingestion, inhalation, dermal absorption, and iatrogenic introduction, with growing evidence that these particles can accumulate in the ovaries, oocytes, and placental tissue. Experimental studies in rodents demonstrate that MPs and NPs induce oxidative stress, trigger inflammatory responses, and promote granulosa cell apoptosis, ultimately diminishing ovarian reserve and impairing folliculogenesis. Clinical and pilot human studies have confirmed the presence of MPs in placentas, umbilical cord blood, and meconium, indicating exposure from the earliest stages of development. Moreover, MPs and NPs may disrupt the hypothalamic–pituitary–ovarian axis, contributing to endocrine dysregulation and hormonal imbalance. Analytical methods such as Fourier-transform infrared spectroscopy, Raman spectroscopy, and scanning electron microscopy enable detection of these particles in biological samples, although methodological standardization remains insufficient. This paper summarizes current evidence on the exposure pathways, toxicological effects, and reproductive consequences of MPs and NPs in women. It further highlights existing research gaps and evaluates available analytical approaches to support future studies and develop strategies aimed at mitigating their detrimental impact on women’s reproductive health and fertility. Full article

Salt stress causes harm to plants through multiple aspects, such as osmotic pressure, ion poisoning, nutrient imbalance, and oxidative damage. Zinc finger proteins harboring two B-box domains, known as double B-box (DBB) proteins, constitute the DBB family. While DBB genes have been implicated in regulating circadian rhythms and stress responses in various plant species, their functions in cotton remain largely unexplored. The present study characterized the DBB gene family across the genomes of Gossypium hirsutum L., Gossypium raimondii L., and Gossypium arboreum L., revealing a complement of 58 members. These DBB genes were assigned to three separate clades based on phylogenetic analysis. Members possessing close phylogenetic relationships have similar conserved protein motifs and gene structures. All DBB proteins were predicted to be nuclear-localized, consistent with their roles as transcription factors. Furthermore, the presence of multiple cis-acting elements related to light, hormone, and stress responses in the promoters implies that GhDBBs are integral to cotton’s environmental stress adaptation. Expression pattern analysis indicated that the expression of GhDBB genes was associated with the plant’s response to multiple abiotic stresses, such as salt, drought, heat (37 °C), and cold (4 °C). The reliability of the expression data was confirmed by qPCR analysis of eight selected GhDBBs. Under 200 mM NaCl, Arabidopsis plants overexpressing GhDBB22 displayed longer roots and healthier true leaves than the wild-type controls. Conversely, VIGS-mediated silencing of GhDBB22 in G. hirsutum led to significantly reduced salt tolerance, accompanied by exacerbated oxidative damage. Taken together, the findings from our integrated genomic and functional analyses provide a foundational understanding of the molecular mechanisms through which proteins encoded by DBB genes are involved in the plant’s response to salt stress. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder characterized by immune dysregulation, metabolic impairments, neuroendocrine disturbances, endothelial dysfunction, and gastrointestinal abnormalities. Immune alterations include reduced natural killer cell cytotoxicity, T-cell exhaustion, abnormal B-cell subsets, and the presence of diverse autoantibodies, suggesting an autoimmune component. Gut dysbiosis and increased intestinal permeability may promote systemic inflammation and contribute to neurocognitive symptoms via the gut–brain axis. Neuroendocrine findings such as hypothalamic–pituitary–adrenal (HPA) axis hypofunction and altered thyroid hormone metabolism further compound metabolic and immune abnormalities. Metabolomic and mitochondrial studies identify impaired ATP generation, redox imbalance, and compensatory shifts toward alternative energy pathways underlying hallmark symptoms like post-exertional malaise. Endothelial dysfunction driven by oxidative and nitrosative stress, along with autoantibody-mediated receptor interference, may explain orthostatic intolerance and impaired perfusion. Collectively, ME/CFS appears to arise from a self-sustaining cycle of chronic inflammation, metabolic insufficiency, and neuroimmune imbalance. Full article