Search Results (540)

Stroke is a leading global cause of mortality and long-term disability, with cerebral edema constituting a major contributor to early neurological deterioration and poor outcomes. Aquaporin-4 (AQP4), the predominant water channel in the central nervous system, plays a paradoxical role in stroke-related brain edema, facilitating both the formation and clearance of excess fluid depending on the pathological context. This review explores the biphasic function of AQP4 across cytotoxic and vasogenic edema, emphasizing its dynamic regulation, subcellular localization, and implications for therapeutic intervention. Evidence from rodent models shows that AQP4 exacerbates cytotoxic edema in acute ischemia by promoting intracellular water influx into astrocytes, whereas in vasogenic edema, it supports fluid reabsorption and glymphatic clearance, thereby alleviating brain swelling. Human studies corroborate AQP4 upregulation in infarcted regions and suggest a potential role for AQP4 polymorphisms and circulating levels as biomarkers of stroke severity and outcome, although larger cohorts and more robust methodological designs are needed. This review also discusses emerging pharmacological strategies to modulate AQP4 activity, including inhibitors, trafficking modulators, and gene-targeted delivery systems, while highlighting challenges in achieving phase-specific modulation. Given its central role in both injury and recovery, AQP4 emerges as a promising yet complex therapeutic target for personalized management of stroke-induced brain edema. Future directions include real-time imaging of AQP4 function, genotype-stratified clinical trials, and integration of AQP4 modulation with current stroke treatment protocols. Full article

Aquaporins (AQPs) are membrane proteins that facilitate the transport of water and solutes. Among AQPs, plasma membrane intrinsic proteins (PIPs) play a critical role in maintaining water balance between the internal and external cell environments. This study focuses on the tomato due to its economic importance and cultivation under moderate salinity conditions in Japan. A swelling assay using X. laevis oocyte confirmed that all five examined tomato SlPIP2 isoforms showed water transport activity. Among them, two-electrode voltage clamp (TEVC) experiments showed that only SlPIP2;1, SlPIP2;4, and SlPIP2;8 transport Na⁺ and K⁺, with no transport activity for Cs⁺, Rb⁺, Li⁺, or Cl⁻. CaCl₂ (1.8 mM) reduced ionic currents by approximately 45% compared to 30 µM free-Ca²⁺. These isoforms function as very low-affinity Na⁺ and K⁺ transporters. Expression analysis showed that SlPIP2;4 and SlPIP2;8 had low, stable expression, while SlPIP2;1 was strongly upregulated in roots NaCl treatment (200 mM, 17days), suggesting distinct physiological roles for these ion-conducting AQPs (icAQPs). These data hypothesized that tomato icAQPs play a critical role in ion homeostasis, particularly under salinity stress. In conclusion, the first icAQPs have been identified in the dicotyledonous crop. These icAQPs are essential for plant resilience under salt stress. Full article

Background and Objectives: Acute normovolemic hemodilution (ANH) is commonly used to minimize perioperative blood loss and transfusion requirements. While it is considered safe, the molecular effects of ANH on vital organs remain unclear. Aquaporins (AQPs), the principal cellular water transporters, may play a role in tissue adaptation or injury under hemodilution stress. This study aimed to evaluate the impact of ANH on AQP1, AQP3, and AQP4 expression profiles and their association with apoptotic and inflammatory markers in the aorta, heart, kidney, and liver. Materials and Methods: Male Hannover–Sprague Dawley rats (6 months old) were assigned to control (no procedure), sham (anesthesia only), and hemodilution (anesthesia and ANH) groups. ANH was induced using balanced crystalloid infusion. Physiological parameters, blood gases, electrolytes, and metabolic profiles were monitored. At 24 h post-ANH, tissues were harvested for immunoblot analysis of AQPs, as well as apoptotic and inflammatory markers. Results: At 24 h post-ANH, changes in potassium, calcium, and glucose levels, decreased hematocrit, increased lactate, decreased pH, base excess, and PaCO₂ were detected, indicating mild metabolic acidosis due to tissue hypoxia and impaired oxygen delivery. Apoptotic and inflammatory responses were observed across all tissues, but AQP alterations were organ-specific. In the heart, AQP1 downregulation correlated inversely with NF-κB and TNF-α levels, while AQP3 upregulation positively correlated with apoptosis. The aorta showed the opposite pattern. In the kidney, AQP4 downregulation was strongly associated with apoptosis and inflammation. Furthermore, ANH selectively increased the AQP3 expression without affecting AQP1 or AQP4 in the liver. Conclusion: ANH induces differential aquaporin expression patterns in major organs, with tissue-specific associations with apoptosis and inflammation. These findings highlight a potential mechanistic role for AQPs, particularly AQP1 and AQP3, in modulating tissue response to hemodilution. These molecular adaptations may serve as early indicators of tissue stress, suggesting clinical relevance for perioperative fluid strategies. Full article

Litopenaeus vannamei, commonly known as the Pacific white shrimp, is one of the most economically significant species in global aquaculture, valued for its rapid growth and adaptability. However, the mechanisms regulating its growth, especially under high-density farming and environmental stress, remain poorly understood. Previous study predicted that LvSlc12A2 was involved in growth regulation. To further reveal the function of this gene in the growth regulation of the whiteleg shrimp, in this study, we explore its function using RT-qPCR, RNA interference, overexpression, and tissue in situ hybridization. RT-qPCR results showed that LvSlc12A2 was highly expressed in gills (about 62%), followed by the hepatopancreas, with the lowest expression in muscle (0.08%, compared to the gills). Myostatin (LvMstn) was mainly expressed in the heart, and molt-inhibiting hormone (LvMIH) in the ventral nerve. In situ hybridization of gill tissues using the mRNA of the gene as a probe revealed strong LvSlc12A2 signals in the gill stratum and epithelial cells. Overexpression of LvSlc12A2, significantly decreased the osmotic gene aquaporin (LvAqp), while knockdown increased its expression. Additionally, levels of growth-related inhibitory genes LvMstn and LvMIH increased significantly after LvSlc12A2 overexpression and were downregulated after its knockdown, suggesting LvSlc12A2 negatively regulates growth, possibly in synergy with LvMstn and LvMIH. These findings indicate LvSlc12A2 influences growth both by negative regulation and by modulating osmotic balance in gill tissues. Full article

Dura mater plays a critical role in neurofluid homeostasis, yet comparative data on capillary network density and organization between cranial and spinal regions remain limited. This study addresses this gap by systematically analyzing capillary architecture and aquaporin (AQP) expression in porcine cranial (parietal, falx) and spinal dura mater. Immunofluorescence labeling and confocal microscopy were used to assess capillary density, spatial distribution, and AQP1/AQP4 expression patterns across over 1000 capillaries in these regions. Cranial dura exhibited a 3–4 times higher capillary density compared to spinal dura, with capillaries predominantly localized to meningeal–dural border cell interfaces in cranial regions and a more dispersed distribution in spinal dura. Both AQP1 and AQP4 were detected as discrete clusters within capillary walls, with higher expression in cranial compared to spinal dura. Lymphatic vessels (PDPN-positive) were also observed adjacent to capillaries, supporting a dual-system model for fluid and waste exchange. These findings highlight the dura’s region-specific vascular specialization, with cranial regions favoring dense, structured capillary networks suited for active fluid exchange. This work establishes a foundation for investigating capillary-driven fluid dynamics in pathological states like subdural hematomas or hydrocephalus. Full article

Bassia scoparia (Syn. Kochia scoparia (L.) Schrad.) is a medicinal plant whose fruit, Kochiae Fructus, has been extensively studied for its dermatological applications. This study focused on extracts from the whole plant B. scoparia (WPBS), excluding fruits, to address the research gap regarding the medicinal properties of non-fruit parts. The diverse skin benefits of WPBS, including its anti-photoaging, moisturizing, wound healing, anti-inflammatory, and anti-angiogenic effects, were investigated. The WPBS extract enhanced the viability of keratinocytes (HaCaT) without inducing cytotoxic effects. WPBS significantly reduced matrix metalloproteinase-1 (MMP-1) levels and increased collagen type I alpha 1 (COL1A1) levels (p < 0.01) in fibroblasts exposed to ultraviolet B (UVB) radiation, indicating strong anti-photoaging effects. WPBS upregulated skin hydration markers such as aquaporin-3 (AQP3) and hyaluronan synthase-3 (HAS3) and effectively accelerated fibroblast wound closure compared to the positive control. Furthermore, WPBS substantially downregulated the expression of inflammatory (COX-2 and IL-1β) and angiogenic markers (VEGF). Transcriptome analysis (RNA-seq) confirmed that WPBS suppressed inflammation-related and UV-induced gene expression pathways. Overall, these findings expand the therapeutic scope of B. scoparia beyond its traditional fruit use and suggest that WPBS is a promising botanical ingredient for various skin applications. Full article

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article

Objective: To investigate the effects of oat fiber on animal constipation and elucidate its underlying mechanisms. Methods: Male BALB/c mice were randomly allocated into five groups: control group (CON), model control group (MODEL), low dose group (LOW), middle dose group (MIDDLE), high dose group (HIGH). Constipation was induced in the mice by intragastric administration of loperamide. Subsequently, the mice (except those in the CON and MODEL groups) were administered oat fiber intragastrically for 21 consecutive days. Results: Compared with the MODEL group, oat fiber significantly increased the number of fecal pellets, fecal wet weight, and fecal water content (p < 0.05), shortened the time to first black stool excretion (p < 0.05), and enhanced the small intestinal propulsion rate in constipated mice. Additionally, oat fiber significantly upregulated motilin (MTL) and gastrin (GAS) levels (p < 0.05), while downregulating vasoactive intestinal peptide (VIP) and somatostatin (SS) levels (p < 0.05). It also significantly reduced the transcription level of Aquaporin 8 (AQP8) (p < 0.05), effectively alleviating intestinal mucosal injury and immune inflammation. The relative expression levels of TNF-α and IL-1β were significantly decreased in the oat fiber group (p < 0.05). Gut microbiota analysis revealed that oat fiber increased both the abundance and diversity of gut microbiota in constipated mice. Specifically, oat fiber was found to enhance the relative abundance of Firmicutes while reducing that of Bacteroidetes. At the genus level, it promoted the proliferation of Lachnospiraceae_NK4A136_group and Roseburia. Conclusions: Oat fiber alleviates constipation in mice by modulating gastrointestinal regulatory peptides, gut microbiota, aquaporin and mitigating intestinal barrier damage and immune-inflammatory responses. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

Oxidative stress is a key mediator of physiological dysfunction in aquatic organisms under environmental challenges, yet its comprehensive impacts on gill physiology require further clarification. This study investigated the molecular and cellular responses of Eriocheir sinensis gills to hydrogen peroxide (H₂O₂)-induced oxidative stress, integrating antioxidant defense, ion transport regulation, and stress-induced cell apoptosis and autophagy. Morphological alterations in the gill filaments were observed, characterized by septum degeneration, accumulation of haemolymph cells, and pronounced swelling. For antioxidant enzymes like catalase (CAT) and glutathione peroxidase (GPx), activities were enhanced, while superoxide dismutase (SOD) activity was reduced following 48 h of exposure. Overall, the total antioxidant capacity (T-AOC) showed a significant increase. The elevated concentrations of malondialdehyde (MDA) and H₂O₂ indicated oxidative stress. Ion transport genes displayed distinct transcription patterns: Na⁺-K⁺-2Cl⁻ co-transporter-1 (NKCC1), Na⁺/H⁺ exchanger 3 (NHE3), aquaporin 7 (AQP7), and chloride channel protein 2 (CLC2) were significantly upregulated; the α-subunit of Na⁺/K⁺-ATPase (NKAα) and carbonic anhydrase (CA) displayed an initial increase followed by decline; whereas vacuolar-type ATPase (VATP) consistently decreased, suggesting compensatory mechanisms to maintain osmotic balance. Concurrently, H₂O₂ triggered apoptosis (Bcl2, Caspase-3/8) and autophagy (beclin-1, ATG7), likely mediated by MAPK and AMPK signaling pathways. These findings reveal a coordinated yet adaptive response of crab gills to oxidative stress, providing new insights into the mechanistic basis of environmental stress tolerance in crustaceans. Full article

The fungal kingdom, with an estimated five million species, has undergone extensive diversification over the past billion years and now occupies a wide array of ecological niches from terrestrial to aquatic ecosystems. To thrive in such diverse environments, fungi must exhibit finely tuned physiological and morphological responses orchestrated by conserved molecular pathways. Increasing evidence suggests that aquaporins (AQPs) play a key role in mediating these adaptive responses, particularly under varying abiotic and biotic stress conditions. However, despite notable advances in recent decades, the precise functional roles of AQPs within the fungal kingdom remains largely unresolved in the field of cell biology. AQPs are transmembrane proteins belonging to the major intrinsic proteins (MIPs) superfamily, which is characterized by remarkable sequence and structural diversity. Beyond their established function in facilitating water transport, MIPs mediated the bidirectional diffusion of a range of small inorganic and organic solutes, ions, and gases across cellular membranes. In fungi, MIPs are classified into three main subfamilies: orthodox (i.e., classical) AQPs, aquaglyceroporins (AQGP), and X-intrinsic proteins (XIPs). This review provides a concise summary of the fundamental structural and functional characteristics of fungal aquaporins, including their structure, classification, and known physiological roles. While the majority of the current literature has focused on the aquaporin and aquaglyceroporin subfamilies, this review also aims to offer a comprehensive and original overview of the relatively understudied X-intrinsic protein subfamily, highlighting its potential implication in fungal biology. Full article

Epidemiological studies identified insufficient and poor-quality sleep as independent risk factors for multiple sclerosis (MS). The glymphatic system, active during slow-wave sleep, clears brain waste through perivascular astrocytic aquaporin-4 (AQP4) channels. The presence of antigens induces a transient, physiological lowering of glymphatic flux as a first step of an inflammatory response. A possible hypothesis linking infection with the Epstein–Barr virus, a well identified causal step in MS, and the development of the disease is that mechanisms such as poor sleep or less functional AQP4 polymorphisms may sustain glymphatic flow reduction. Such chronic glymphatic reduction would trigger a vicious circle in which the persistence of antigens and an inflammatory response maintains glymphatic dysfunction. In addition, viral proteins that persist in demyelinated plaques can depolarize AQP4, further restricting waste elimination and sustaining local inflammation. This review examines the epidemiological evidence connecting sleep and MS risk, and the mechanistic findings showing how poor sleep and other glymphatic modulators heighten inflammatory signaling implicated in MS pathogenesis. Deepening knowledge of glymphatic functioning in MS could open new avenues for personalized prevention and therapy. Full article

Sigma1 receptor (S1R) and some aquaporins (AQPs) are involved in controlling oxidative stress, but only recently has their possible interaction emerged. S1R acts by interacting with proteins in the plasma membrane and organelles and AQPs by favoring the hydrogen peroxide (H₂O₂) cell removal. To date, the possible regulation of peroxiporins by S1R has not been explored. Using H₂O₂ HyPer7 biosensors and knockdown techniques, we investigated (1) the AQPs and S1R functional involvement in H₂O₂ diffusion through the plasma membrane and in the outer and inner mitochondrial membranes, and (2) the possible interaction between S1R and AQPs. Our data showed the functional involvement of different AQPs in the diffusion of H₂O₂: AQP3, AQP6, and AQP8 in the plasma membrane; AQP6 in the outer mitochondrial membrane; and AQP6 and AQP8 in the inner mitochondrial membrane. The knockdown of S1R demonstrated its involvement in the overall diffusion of H₂O₂ across the three compartments. The double knockdown of S1R and a single AQP indicated that AQP8 and AQP6 could be regulated by S1R. These findings demonstrate the coordinated role of AQPs in the mitochondria and the plasma membranes and that S1R modulates the AQP-facilitated H₂O₂ cell removal, thus controlling the oxidative status and, most likely, the oxidative stress. Full article

Background: Aquaporins (AQPs) are integral membrane proteins that facilitate water transport across biological membranes. While their role is well-characterized in various tissues, their function in the oral cavity remains poorly understood. Saliva is an easily accessible, non-invasive biofluid that contains stable extracellular RNA and can reflect both systemic and local physiological or pathological processes, making it a promising source for RNA analyses. This study investigates AQP mRNA levels in human saliva. Methods: Saliva samples were collected from patients of a dental practice and analyzed using quantitative PCR to detect AQP levels. An in silico analysis of AQPs in cells of the oral cavity were performed. Baseline data of the patients were recorded. Results: Our findings demonstrate the presence of multiple AQP subtypes in human saliva. AQP5 was the most abundant, followed by AQP9 and AQP1. The levels of several AQPs showed intercorrelation, whereas AQP3 appeared to be independently regulated and did not correlate with the other AQPs. Conclusions: This study demonstrates that differential AQP mRNA levels can be detected in human saliva. These findings suggest that salivary AQP mRNA may serve as surrogate markers for altered AQP levels in cells of the oral cavity. In the future, such patterns of AQP levels could potentially be used to identify or monitor pathological conditions affecting the oral mucosa or salivary glands. Further studies are required to validate this approach and to understand its diagnostic relevance. Full article

Dendrobium, a prominent genus in the Orchidaceae family, has generated significant research attention due to its demonstrated biological potential, particularly its notable anti-inflammatory and antioxidant activities. In this study, two fractions of fermented Dendrobium officinale polysaccharides (FDOPs) were successfully isolated through a multi-stage purification strategy including gradient ethanol precipitation, gel column chromatography, and ion exchange chromatography with Lactobacillus reuteri CCFM863. Structural characterization revealed that both Dendrobium officinale polysaccharide fractions consisted of (1→4)-β-D-Manp, (1→4)-β-D-Glcp, and (1→4)-α-D-Glcp residues. The anti-inflammatory efficacy and keratinocyte-protective potential of FDOPs (FDOP-1A and FDOP-2A) were investigated by using lipopolysaccharide (LPS)-induced RAW264.7 and HaCaT cells models, which showed significant inhibitions on the inflammatory factors of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and interleukin-1 beta (IL-1β); recovered levels of filaggrin (FLG), aquaporin 3 (AQP3), transient receptor potential vanilloid 4 (TRPV4), cathelicidin antimicrobial peptide (CAMP)/LL-37, and adiponectin (ADIPOQ); and the reduced protein expression of the TLR4/IκB-α/NF-κB/NLRP3 pathway. Notably, the FDOPs exhibited a remarkable reactive oxygen species (ROS) scavenging capacity, demonstrating superior antioxidant activity. Therefore, FDOPs show dual anti-inflammatory and antioxidant properties, making them suitable as active ingredients for modulating epidermal inflammation and promoting skin barrier repair. Full article