Search Results (178)

This systematic review assessed transcriptomic evidence on the molecular mechanisms underlying spontaneous preterm birth (sPTB). Major electronic databases were searched from inception to October 2025. Eligible studies examined RNA transcriptomic profiles from maternal pregnancy-related tissues or biofluids in spontaneous preterm labor (sPTL) or preterm prelabor rupture of membranes (PPROM), while indicated or iatrogenic preterm births were excluded. Two reviewers independently screened studies, extracted differentially expressed genes (DEGs), and assessed study quality. DEGs were summarized by tissue type, and recurrent concordant genes were analyzed using Gene Ontology, Reactome, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, with false discovery rate < 0.05 considered significant. Twenty studies were included. Transcriptomic data were derived from placental villi, maternal peripheral blood, decidua, fetal membranes, myometrium, amniotic fluid, and vaginal secretions. Placental villi findings suggested proliferative-metabolic reprogramming and impaired maternal–fetal immune–structural homeostasis, whereas maternal blood profiles reflected systemic immune–inflammatory activation and dysregulated lipid-metabolic pathways. sPTL and PPROM showed potentially distinct signatures involving extracellular matrix disruption, collagen remodeling, matrix degradation, and myeloid/neutrophil-associated inflammation. Transcriptomic profiling may support non-invasive sPTB risk assessment, but standardized, phenotype-specific longitudinal studies are needed to confirm predictive value and clinical utility. Full article

Background: Early-onset neonatal listeriosis is a rare, life-threatening infection of vertical origin caused by Listeria monocytogenes. First-line therapy is intravenous ampicillin combined with an aminoglycoside; acquired β-lactam resistance is exceptionally uncommon. Case Presentation: A 34-week preterm female neonate (birth weight 1990 g, appropriate for gestational age) was born to a febrile primigravida with fetid greenish amniotic fluid at a regional secondary maternity and transferred at 30 h of life to our tertiary NICU with respiratory failure requiring mechanical ventilation. L. monocytogenes was recovered from blood, gastric aspirate, pharyngeal exudate, ocular secretion, and skin swab. Gradient strip susceptibility testing reported ampicillin and trimethoprim–sulfamethoxazole non-susceptibility, although confirmatory broth microdilution was unavailable. Broad-spectrum empirical therapy was revised on Day 5 to include ampicillin–sulbactam, with piperacillin–tazobactam and gentamicin continued. A follow-up blood culture on Day 9 remained sterile through 7 days. The hospital course was complicated by thrombocytopenia, transiently elevated aminotransferases, and a Grade I subependymal hemorrhage; tertiary NICU length of stay was 25 days. Conclusions: Recovery under a multi-agent regimen precludes attribution of effect to any single component. Discordant gradient strip susceptibility results in L. monocytogenes should be confirmed by broth microdilution before any therapeutic change; survivors of severe early-onset listeriosis require structured multidisciplinary follow-up. Full article

Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The most common types—type 1 and type 2 diabetes—have different etiologies and pathophysiological mechanisms. Type 1 diabetes (T1DM) results from autoimmune destruction of the insulin-producing pancreatic β-cells, leading to the development of absolute insulin deficiency, whereas in type 2 diabetes (T2DM), impaired carbohydrate metabolism is primarily caused by insulin resistance and relative insulin deficiency. Current diagnostic criteria do not allow for the detection of the disease at the preclinical stage. MicroRNA (miRNA) influences post-translational regulation of gene expression by inhibiting mRNA translation and also promotes mRNA degradation. The aim of this review is to summarize current evidence on the role of microRNAs in the pathogenesis of T1DM and T2DM and to evaluate their potential as early diagnostic biomarkers and therapeutic targets. It is demonstrated that T1DM and T2DM exhibit altered expression of specific microRNAs involved in β-cell apoptosis, autoimmune inflammation, and insulin signaling. In T1DM, key miRNAs include miR-21, miR-25, miR-146a, and miR-375, which reflect β-cell destruction and the autoimmune process. In T2DM, critical roles are played by miR-9, miR-29, miR-34a, miR-103/107, miR-126, miR-143, and miR-375, which regulate insulin secretion, lipid metabolism, and tissue insulin sensitivity. Particular attention is given to microRNAs whose expression changes several years before clinical disease onset (miR-15a, miR-126, miR-375), offering opportunities for early diagnosis. Data are presented on circulating miRNAs in stable biological fluids (blood, urine). It should be emphasized, however, that the proposed microRNA panel currently represents only a potential diagnostic tool. This panel requires further validation and confirmation by clinicians in large-scale prospective studies and does not yet claim to be ready for routine clinical use. Nevertheless, the development of such a universal microRNA panel, followed by thorough clinical evaluation, has promising biomedical potential, which will not only allow for the diagnosis of diabetes at an early stage but also identify new therapeutic targets for personalized medicine. Full article

Temporomandibular disorders (TMDs) are the prevalent causes of orofacial pain and dysfunction of the temporomandibular joint (TMJ) and masticatory muscles. Previous studies have revealed that proinflammatory cytokines play a key role in promoting inflammation, pain, and degeneration within the TMJ. In this context, the present systematic review synthesizes current evidence on various cytokines involved in the pathophysiology of TMDs and evaluates their associations with clinical signs and structural TMJ damage. A PRISMA-guided search (PROSPERO: CRD420251163290) was conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library to identify human-based, in vivo, and in vitro studies (January 2014 to September 2025) that assessed the roles of proinflammatory cytokines in TMDs. The following data were extracted from the identified studies: cytokine profiles, sampling methods, clinical outcomes, and TMJ structural changes. Study quality and risk of bias were systematically evaluated. A total of 15 studies (clinical, animal, and mechanistic) were included in the review. Tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) consistently emerged as the major contributors to synovitis, cartilage degradation, nociceptive sensitization, and bone resorption. Human studies showed that high levels of TNF-α, IL-1β, and IL-6 and chemokines such as C-C motif chemokine ligand 2 (CCL2) and regulated on activation, normal T-cell expressed and secreted (RANTES) were associated with TMJ pain, restricted mandibular motion, crepitus, malocclusion, and erosive changes on imaging. An increased ratio of TNF to soluble TNF receptor in synovial fluid correlated with both pain and condylar damage, suggesting that loss of cytokine control contributes to progressive joint destruction. TMDs, particularly inflammatory and degenerative subtypes, are cytokine-driven pathologies rather than purely mechanical disorders. TNF-α, IL-1β, and IL-6 are the promising candidate biomarkers of local inflammation and structural joint pathology. Standardized longitudinal studies are required to validate cytokine-based diagnostics and develop anti-cytokine therapeutics. Full article

Elevated temperatures are frequently encountered in numerous occupational settings such as iron and steel foundries, non-ferrous metal foundries, brick and ceramic manufacturing plants, glass production facilities, rubber factories, electrical power plants, bakeries, laundries, chemical processing sites, mining operations, smelting plants, and steam tunnels. Employees working in these environments are at risk of developing various health issues and injuries, including ocular complications, due to prolonged exposure to heat and the physical demands of handling heavy materials. This study focuses on examining the pressure within the eye’s anterior chamber, referred to as Intraocular Pressure (IOP), and its association with the cornea’s biomechanical characteristics, with particular attention to corneal temperature. Our methodology is grounded in the principles of the first law of thermodynamics. The findings reveal a link between the temperature of the eye’s anterior chamber and the biomechanical behaviour of the cornea. Specifically, IOP serves as an indicator of the cornea’s elasticity and its optical properties as influenced by temperature variations. We investigated how the cornea’s elastic energy, or the work it performs, varies with temperature changes. The results show that an increase in temperature corresponds to a reduction in the work exerted by the cornea. The corneal temperature is affected by both the ambient environment and the temperature of the aqueous humour within the anterior chamber. This indicates a relationship between the mechanical work done by the cornea and the pressure exerted by the fluid in the eye’s front segment. Furthermore, our study identified a correlation between corneal thickness and IOP, which our modelling approach successfully quantifies. Utilizing the first law of thermodynamics, we calculated the work performed by the anterior chamber against the cornea’s internal surface. Temperature fluctuations influence the secretion, drainage, and flow characteristics of the aqueous humour, thereby impacting IOP and associated ocular conditions. These insights are valuable for devising strategies aimed at preventing eye injuries among workers exposed to high-temperature environments. Full article

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a leading cause of euvolaemic hyponatraemia and remains challenging to manage due to limitations of existing therapies, including poor adherence to fluid restriction and safety concerns associated with vasopressin receptor antagonists and demeclocycline. Recent mechanistic and clinical evidence suggests that sodium–glucose cotransporter-2 (SGLT2) inhibitors may offer a novel therapeutic approach by promoting osmotic diuresis and increasing electrolyte-free water clearance. This narrative review synthesises current pathophysiological understanding and emerging clinical evidence regarding the role of SGLT2 inhibitors in SIADH-related hyponatraemia. We examine how their proximal tubular mechanism differs from conventional therapies such as loop diuretics, vaptans, and salt supplementation, and evaluate evidence from recent randomised and crossover trials demonstrating improved serum sodium and enhanced water excretion with empagliflozin and dapagliflozin. SGLT2 inhibitors represent a physiologically rational and potentially safer alternative in selected patients with SIADH, particularly where fluid restriction is poorly tolerated or ineffective. Although further large-scale studies are required to define their optimal positioning within treatment algorithms, current evidence supports their potential role as an emerging therapeutic option in SIADH management. Full article

Salivary glands produce saliva through precisely coordinated epithelial ion transport processes. Ion channels are essential components of the molecular machinery that convert neural and hormonal signals into targeted ion and water flux. This review focuses on the integrated molecular and cellular mechanisms by which ion channels cooperate to generate salivary fluid under physiological conditions. Saliva formation proceeds through two sequential stages: isotonic primary fluid secretion by acinar cells, followed by ionic modification within the ductal epithelium. Parasympathetic stimulation activates muscarinic M1/3 receptors, initiating intracellular calcium signaling through inositol 1,4,5-trisphosphate-dependent release from the endoplasmic reticulum and sustained calcium entry via Orai1/TRPC channels. Elevated cytosolic calcium activates apical ANO1/TMEM16A chloride channels, the rate-limiting step in acinar fluid secretion, together with basolateral calcium-activated potassium channels that preserve the electrochemical driving force for chloride efflux. Chloride accumulation is maintained by Na⁺/K⁺-ATPase and the Na⁺-K⁺-2Cl⁻ cotransporter, while osmotic gradients drive water movement through apical aquaporin-5 and basolateral aquaporin-1/3. As primary saliva traverses the ductal system, epithelial sodium channels, CFTR, and additional ion transport pathways reabsorb sodium and chloride and secrete potassium and bicarbonate, producing hypotonic final saliva. By synthesizing calcium signaling, chloride and potassium conductance, sodium handling, and epithelial polarity into a unified framework, this review establishes ion channel integration as the fundamental basis of salivary gland fluid secretion. Full article

Alzheimer’s disease (AD) is a major public health issue, and the role of peripheral immunity in its pathogenesis remains poorly understood. This study conducted a comprehensive reanalysis of publicly available single-cell transcriptomic and chromatin accessibility datasets to investigate immune cell dynamics in AD. By integrating data from cerebrospinal fluid and peripheral blood samples, we constructed a cross-tissue immune cell atlas. Based on Monocle3 pseudotemporal trajectory analysis, we propose the hypothesis that CD8⁺ TEMRA cells in the cerebrospinal fluid may originate from blood-derived CD8⁺ TPex cells. Furthermore, cell–cell communication analysis revealed a potential interaction mechanism whereby CD8⁺ TPex cells secrete MIF signals to activate monocytes, prompting them to release increased levels of inflammatory factors (IL1B) and adhesion molecules (ICAM1). These inflammatory factors collectively contribute to the disruption of the blood–brain barrier, thereby facilitating immune cell infiltration. Our reanalysis provides a novel interpretation of existing data, establishes a regulatory framework for understanding immune infiltration in AD. Full article

Bacterial pathogens exploit host-derived nutrients to coordinate metabolism and virulence determinants to optimize fitness in vivo. In Pseudomonas aeruginosa, GlnK is a central regulator of nitrogen metabolism. It senses the intracellular nitrogen status by integrating 2-oxoglutarate (2-OG) and glutamine signals, which in turn triggers its uridylylation and conformational changes. This reversible post-translational modification modulates its interaction with target proteins, thereby precisely regulating carbon-nitrogen metabolic homeostasis and enabling adaptive nitrogen metabolism in response to host-derived nutrient cues. In this study, we found that glnK is upregulated during infection in a mouse pneumonia model. By growing bacteria in mouse bronchoalveolar lavage fluid (BALF), we demonstrated that the expression of glnK is activated by the NtrB-NtrC two-component regulatory system in response to the host nutrient environment. Mutation of glnK impairs bacterial virulence. Transcriptomic analysis revealed downregulation of the type III secretion system (T3SS) genes in the glnK mutant. Further studies revealed a role of GlnK in maintaining the homeostasis of the NtrB-NtrC system through a negative feedback mechanism, which is required for the expression of the T3SS genes. Collectively, these findings reveal a role of GlnK in interconnecting carbon–nitrogen balance and the T3SS in response to the host environment. Full article

Cystic fibrosis (CF) is caused by loss-of-function variants in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride and bicarbonate channel and affects multiple organs, with pancreatic involvement showing very high penetrance. In pancreatic ducts, CFTR drives secretion of alkaline, bicarbonate-rich fluid that maintains intraductal patency, neutralises gastric acid and permits safe delivery of digestive enzymes. Selective impairment of CFTR-dependent bicarbonate transport, even in the presence of residual chloride conductance, is strongly associated with exocrine pancreatic insufficiency, recurrent pancreatitis and cystic-fibrosis-related diabetes. These clinical manifestations are captured by pharmacodynamic anchors such as faecal elastase-1, steatorrhoea, pancreatitis burden and glycaemic control, providing clinically meaningful benchmarks for CFTR-targeted therapies. In this review, we summarise the principal mechanisms underlying pancreatic pathophysiology and the current approaches to clinical management. We then examine in vitro pancreatic duct models that are used to evaluate small molecules and emerging therapeutics targeting CFTR. These experimental systems include native tissue, primary cultures, organoids, co-cultures and microfluidic devices, each of which has its own advantages and limitations. Intact micro-perfused ducts provide the physiological benchmark for studying luminal pH control and bicarbonate (HCO₃⁻) secretion. Primary pancreatic duct epithelial cells (PDECs) and pancreatic ductal organoids (PDO) preserve ductal identity, patient-specific genotype and key regulatory networks. Immortalised ductal cell lines grown on permeable supports enable scalable screening and structure activity analyses. Co-culture models and organ-on-chip devices incorporate inflammatory, stromal and endocrine components together with flow and shear and provide system-level readouts, including duct-islet communication. Across this complementary toolkit, we prioritise bicarbonate-relevant endpoints, including luminal and intracellular pH and direct measures of HCO₃⁻ flux, to improve alignment between in vitro pharmacology and clinical pancreatic outcomes. The systematic use of complementary models should facilitate the discovery of next-generation CFTR modulators and adjunctive strategies with the greatest potential to protect both exocrine and endocrine pancreatic function in people with CF. Full article

The brain’s extracellular matrix (ECM) serves as a dynamic and instructive regulator of glioma progression. The ECM provides structural support while integrating pharmacological and mechanical signals that influence glioma initiation, progression, and treatment resistance. Deviant ECM remodeling fosters tumor heterogeneity, invasion, and immune evasion by altering stiffness, composition, and cellular matrix signaling. We proposed that ECM remodeling in gliomas not only facilitates tumor growth and heterogeneity but also establishes advantageous biophysical and metabolic conditions that foster treatment resistance and recurrence. Our objective is to analyze current findings regarding the structural, biochemical, and mechanical roles of the brain ECM in glioma growth, emphasizing its contribution to tumor heterogeneity, mechanotransduction, immunological modulation, and its potential as a therapeutic target. Method: A comprehensive literature review was conducted using scientific databases including PubMed, Web of Science, and Scopus. Peer-reviewed literature published between 2000 and 2025 was selected for its relevance to ECM composition, stiffness, remodeling enzymes, extracellular vesicles, and mechanobiological processes in gliomas. Results: Recent investigations demonstrate that glioma cells actively alter the ECM by secreting collagens, laminins, and metalloproteinases, establishing a feedback loop that facilitates invasion and resistance. Discussion: Mechanical variables, such as ECM stiffness and solid stress, influence glioma growth, metabolism, and immune exclusion. Moreover, extracellular vesicles facilitate significant extracellular matrix remodeling and improve communication between tumors and stromal cells. The disruption of ependymal and subventricular extracellular matrix niches enhances invasion and cerebrospinal fluid-mediated signaling. The remodeling of the ECM influences glioma growth through interconnected biochemical, mechanical, and immunological mechanisms. Examining ECM stiffness, crosslinking enzymes, and vesicle-mediated signaling represents a potential therapeutic approach. Integrative methodologies that combine mechanobiology, imaging, and multiomics analysis could uncover ECM-related vulnerabilities to improve glioma treatment. Full article

Most insects secrete special fluids from their tarsal pads which are essential for the function of their attachment systems. Previous studies investigated several physical and chemical characteristics of this pad fluid in different insect species. However, there is not much known about the mechanical properties of fluid from smooth adhesive pads. In this study, we used the stress–relaxation nanoindentation method to examine the viscoelastic properties of pad fluid from Sungaya aeta. Force–displacement and stress–relaxation curves on single fluid droplets were recorded with an atomic force microscope (AFM) and analyzed using Johnson–Kendall–Roberts (JKR) and generalized Maxwell models for determination of effective elastic modulus (E), work of adhesion (Δγ) and dynamic viscosity (η). In addition, we used white light interferometry (WLI) to measure the maximal height of freshly acquired droplets. Our results revealed three different categories of droplets, which we named “almost inviscid”, “viscous” and “rigid”. They are presumably determined at the moment of secretion and retain their characteristics even for several days. The observed mechanical properties suggest a non-uniform composition of different droplets. These findings provide a basis for advancing our understanding about the requirements for adaptive adhesion-mediating fluids and, hence, aid in advancing technical solutions for soft or liquid temporal adhesives and gripping devices. Full article

Traumatic brain injury (TBI) is a common and important cause of morbidity and mortality among pediatric patients, affecting 47–280 per 100,000 children every year. Head trauma can affect the brain not only by the injury itself but also via a neuroinflammatory process, which leads to blood–brain barrier (BBB) disruption, leukocyte infiltration, and edema formation. This process is regulated by several immune mediators, including interleukins (ILs), which are molecules that are currently investigated in both adult and pediatric TBI. In pediatric patients, IL-1β, IL-6, and IL-8 have mainly been investigated, while IL-10 and IL-17 also play a role in the neuroinflammatory cascade. Therefore, the purpose of this review was to examine the role of the aforementioned cytokines in the pathophysiology of pediatric TBI, as well as their role in determining clinical outcome and prognosis. IL-1β is a key pro-inflammatory cytokine in glutamate excitotoxicity post-TBI and in upregulating the expression of additional pro-inflammatory cytokines. Its high levels in cerebrospinal fluid (CSF) are correlated with injury severity and poor outcomes. IL-6 is an anti-inflammatory cytokine, and its concentration rises rapidly after the injury. Current data show that it can be useful in predicting severe TBI (sTBI) in addition to clinical parameters. IL-8 is a cytokine with several pro- and anti-inflammatory properties. On the one hand, it is a potent chemotactic agent, attracting inflammatory cells to the injured area, and it plays a role in BBB disruption. On the other hand, it promotes the survival of cholinergic and hippocampal neurons via the secretion of nerve growth factor (NGF). These cytokines are important in predicting the outcome of pediatric patients with TBI, as well as in predicting several post-TBI conditions such as fatigue and epilepsy, thus improving diagnostic ability and timely treatment. Further research, unraveling the complex mechanisms via which post-TBI neuroinflammation occurs, will lead to targeted therapies and better outcomes overall. Full article

Late-night feeding, defined in the present review as feeding after 8:00 pm when evening insulin secretion and sensitivity are low, is increasingly prevalent in Western society and is recognized as a disruptor of metabolic homeostasis. Yet health problems related to late-night feeding are largely ignored in time-restricted feeding studies that generally do not extend past an 8:00 pm feeding window. This paper proposes a novel cascade linking late-night hyperglycemia with sleep disturbances and nasal congestion mediated by renal sodium retention, increased plasma osmolarity, and stress hormone release by hypothalamic–pituitary–adrenal axis activation. The narrative describes the circadian decline in insulin sensitivity, which amplifies postprandial glucose surges following late-night feeding. Elevated glucose levels drive renal glucose reabsorption via sodium–glucose cotransporters, promoting sodium retention independent of insulin. Increased sodium retention raises extracellular osmolarity, activating hypothalamic osmoreceptors and stimulating the hypothalamic–pituitary–adrenal axis. Cortisol release promotes alertness, while fluid retention and mucosal edema contribute to nasal congestion and early waking. Supine fluid redistribution during sleep further exacerbates airway narrowing, increasing the risk of sleep fragmentation and obstructive sleep apnea. The present paper fills a gap in current time-restricted feeding literature by integrating renal, osmotic, and neuroendocrine pathways that may be overlooked as underlying mechanisms of dysregulated glucose control and hormone dysfunction. Reviewed evidence suggests that symptoms such as nocturnal congestion and sleep disruption are not merely incidental to late-night feeding but frame late night feeding as a risk factor with underlying physiological stressors that could contribute to cardiometabolic risk. Full article

Alzheimer’s disease (AD) has long been viewed primarily as a disorder of abnormal protein accumulation, yet mounting evidence suggests that impaired clearance mechanisms may be critical in driving disease progression. In this review, we propose the concept of the “cerebral clearance cascade” as an integrative framework, describing a dynamic and interconnected system comprising the choroid plexus (CP), cerebrospinal fluid (CSF), interstitial fluid (ISF) dynamics, the glymphatic network, and the blood–brain barrier (BBB). These elements maintain brain proteostasis by regulating the removal of metabolites, neurotoxic proteins, and inflammatory signals and secreting neuroprotective factors. We describe how dysfunction at each node of the cascade contributes to amyloid and tau accumulation, neuroinflammation, vascular pathology, and cognitive decline. While clearance failure has been implicated across several neurodegenerative disorders, here we specifically synthesize evidence in the context of AD and emphasize how disruption of interlinked clearance systems may underlie both the anatomical spread of pathology and clinical heterogeneity. Finally, we outline emerging therapeutic strategies aimed at restoring or enhancing clearance pathways, including plasma and CSF-based interventions, CP-targeted approaches, glymphatic modulation, and BBB-protective strategies. Positioning AD within this broader yet specific “cerebral clearance cascade” perspective deepens our mechanistic understanding and highlights new translational opportunities for disease-modifying therapies. Full article