Expression Of AQP1 Research Articles

3D printing of multifunctional hydrogel scaffolds based on recombinant collagen for bile duct repair

Bile duct injuries remain a significant clinical challenge following hepatobiliary surgeries. Recently, 3D-printed tubular scaffolds have shown promise as effective solutions for bile duct tissue repair. This study presents a novel bi-layered bile duct scaffold, fabricated using advanced three-dimensional printing technology. The inner layer of this scaffold is constructed from poly(ε-caprolactone) methacrylate (PCLMA), which imparts high mechanical strength. The outer layer is composed of biocompatible methacrylated recombinant type I collagen (rColMA) and ε-poly(L-lysine)-methacrylamide (EPLMA), providing excellent antibacterial properties. In addition, encapsulated interleukin-6-loaded liposomes (IL-6@Lip) are incorporated into the outer layer to further promote tissue regeneration. This innovative design creates an optimal microenvironment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into bile duct-like cells. These differentiated cells contribute to bile duct tissue regeneration, as evidenced by the expression of key differentiation markers, including CK7, CK19, AQP1, AE2, and CX43. The rColMA/EPLMA/IL-6@Lip hydrogel in the outer layer of the scaffold significantly enhances BMSC proliferation and their differentiation into bile duct epithelial cells. Furthermore, in vivo experiments show that the PCLMA//rColMA/EPLMA/IL-6@Lip bi-layered scaffold does not induce bile stasis. This novel, pre-differentiated 3D-printed active scaffold offers valuable insights into bile duct tissue regeneration and replacement research.

Non-dioxin-like polychlorinated biphenyls (PCB 101, 153, and 180) and adipocyte lipid dysfunctions: Involvement of glycerol and role of aquaglyceroporins in mature 3T3-L1 cells.

Non-dioxin-like polychlorinated biphenyls (NDL-PCBs), as well as dioxin-like PCBs, are endocrine disruptors that persist in human and animal tissues worldwide. Due to their lipophilicity and resistance to enzymatic degradation, PCBs accumulate in fat deposits contributing to the onset of endocrine and metabolic diseases. Aquaporins (AQPs) are transmembrane channel proteins that allow the transport of water and small solutes. In particular, the aquaglyceroporins AQP3, AQP7, and AQP9 mediate the release and the uptake of glycerol in adipose tissue. Here, we investigate the modulation of these AQPs by NDL-PCBs and the following effects on lipid metabolism in mature 3T3-L1 adipocytes exposed for 48 h to PCB 101, 153, or 180 (1 μM). NDL-PCBs modulated protein expression of AQP3 and AQP7, involved in glycerol release, and AQP9, implicated in glycerol uptake. This modulation induced a greater accumulation of glycerol in treated adipocytes indirectly evaluated by its reduction in the culture media. Interestingly, only PCB 153 altered the expression of enzymes involved in glycerol metabolism and lipid accumulation (i.e. Pparg, Fabp4, Gyk, Dgat1, and Agpat9). These modifications indicated an increase of adipocyte lipid accumulation confirmed by Oil Red O staining. The role of AQPs in the increased cellular accumulation of glycerol was confirmed using phloretin, an AQP9 inhibitor, that reverted the PCB 153 effect. Our results show the involvement of AQPs in PCB 153-induced dysfunction of glycerol metabolism and lipid storage in adipocytes, contributing to better defining the mechanisms underlying its known obesogenic effect.

Sodium tanshinone IIA sulfonate alleviates fetal growth restriction by mediating aquaporin-3 expression in placental trophoblast cells.

Fetal growth restriction (FGR) is characterized by the inability of the fetus to achieve its growth potential due to pathological factors, most commonly impaired placental trophoblast cell function. Currently, effective prevention and treatment methods of FGR are limited. We aimed to explore the pathogenesis of FGR and provide potential strategies for mitigating its occurrence. The case-control study compared AQP3 expression in placental trophoblast cells of pregnant women with FGR and those with normal pregnancies. Then mouse FGR models were induced via cadmium exposure, and placental trophoblast cells (JEG-3) were similarly treated. The study assessed the effects of Sodium tanshinone IIA sulfonate (STS) and the role of the PI3K/Akt pathway in improving AQP3 expression and trophoblast cell function. Placental trophoblast cells in FGR cases exhibited significantly reduced AQP3 expression. AQP3-knockdown cells displayed dysfunction. Cadmium exposure in mice and JEG-3 cells led to decreased AQP3 expression and trophoblast cell dysfunction, both of which were ameliorated by STS. Fetal mouse weight increased with STS treatment. STS upregulated AQP3 expression and improved trophoblast cell function in AQP3-knockdown cells. Inhibiting the PI3K/Akt pathway diminished STS's beneficial effects. ThereforeSTS may enhance AQP3 expression in placental trophoblast cells affected by FGR through the activation of the PI3K/Akt pathway, ultimately bolstering placental trophoblast cell function and alleviating FGR. As above, STS appears to be a potential therapeutic agent for alleviating FGR.

Stem Cell Therapy Modulates Molecular Cues of Vasogenic Edema Following Ischemic Stroke: Role of Sirtuin-1 in Regulating Aquaporin-4 Expression.

Conventional post-stroke edema management strategies are limitedly successful as in multiple cases of hemorrhagic transformation is being reported. Clinically, acute-ischemic-stroke (AIS) intervention by endovascular mesenchymal stem cells (MSCs) have shown benefits by altering various signaling pathways. Our previous studies have reported that intra-arterial administration of 1*105 MSCs (IA-MSCs) were beneficial in alleviating post-stroke edema by modulating PKCδ/MMP9/AQP4 axis and helpful in preserving the integrity of blood-brain-barrier (BBB). However, the role of mitochondrial dysfunction and ROS generation post-AIS cannot be overlooked in context to the alteration of the BBB integrity and edema formation through the activation of inflammatory pathways. The anti-inflammatory activity of IA-MSCs in stroke has been reported to be regulated by sirtuin-1 (SIRT-1). Hence, the relationship between SIRT-1 and AQP4 towards regulation of post-stroke edema needs to be further explored. Therefore, the present study deciphers the molecular events towards AQP4 upregulation, mitochondrial dysfunction and BBB disruption in context to the modulation of SIRT-1/PKCδ/NFκB loop by IA-MSCs administration. Ovariectomized SD rats were subjected to focal ischemia. SIRT-1 activator, SIRT-1 inhibitor, NFkB inhibitor and IA-MSCs were administered at optimized dose. At 24h of reperfusion, behavioral tests were performed, and brains were harvested following euthanasia for molecular studies. IA-MSCs downregulated AQP4, PKCδ and NFkB expression, and upregulated SIRT-1 expression. SIRT-1 upregulation renders mitochondrial protection via reduction of oxidative stress resulting in BBB protection. IA-MSCs can modulate SIRT-1 mediated AQP4 expression via mitochondrial ROS reduction and modification of NFkB transcriptional regulation.

Curcumin administration alleviates seminal vesicle damage in type 1 diabetic rats by promoting AQP8 expression through AR activation

Diabetes is a detriment to male reproductive health, notably through its capacity to diminish secretion from accessory glands such as the seminal vesicles and prostate, which are crucial for reproductive function. Curcumin, a naturally derived polyphenol renowned for its anti-inflammatory and antioxidative attributes, has demonstrated potential in mitigating tissue damage across various organs in diabetic patients. Despite its established benefits, the specific impact of curcumin on seminal vesicle damage in the context of diabetes remains underexplored. This investigation delves into the therapeutic potential of curcumin in ameliorating seminal vesicle damage in diabetic rats, thereby elucidating its underlying mechanisms. This study focused on twenty male SD rats divided into two distinct groups, a control cohort and a diabetic contingent, and employed a streptozocin (STZ)-induced type 1 diabetic rat model to ascertain seminal vesicle alterations secondary to diabetes. Ultrasonography was used to measure rat seminal vesicle sizes for comparison with postdissection measurements. This study revealed that (1) seminal vesicle volume and seminal fluid secretion were reduced in diabetic rats and (2) ultrasonography can predict seminal vesicle secretory dysfunction in diabetic rats, providing a theoretical basis for selecting animal models of diabetic seminal vesicle dysfunction for subsequent studies. Thirty male SD rats were subsequently divided into three groups: control, diabetic, and curcumin-treated. The curcumin group, which was subjected to a one-month-long intervention after STZ-induced diabetes onset, exhibited significant histological and functional recovery. Haematoxylin‒eosin (HE) staining revealed disordered seminal vesicle tissue structures and decreased epithelial cell height in diabetic rats, which was partially restored after curcumin treatment. Western blot and PCR results demonstrated that the expression levels of androgen receptor (AR) and aquaporin (AQP)8 in the seminal vesicle tissues of diabetic rats were decreased, whereas curcumin treatment led to increases in the expression levels of AR and AQP8. Seminal vesicle cells were cultured in vitro and divided into six groups: control, HG, HG-CUR-5 µM, HG-CUR-10 µM, HG-CUR-20 µM, and HG-CUR-50 µM. After 48 h of intervention, the fructose concentration in the culture medium was measured, and the expression of AR and AQP8 in the control, HG, and HG-CUR-20 µM groups was determined via Western blotting and PCR. The results revealed that the expression of AR and APQ8 in high glucose-treated seminal vesicle cells was decreased and that curcumin treatment upregulated the expression of AR and AQP8. After the addition of bicalutamide (an AR inhibitor), the expression of AQP8 was reduced. These findings suggest that curcumin may alleviate seminal vesicle damage in type 1 diabetic rats by activating the AR-AQP8 pathway.

Ligustrazine hydrochloride Prevents Ferroptosis by Activating the NRF2 Signaling Pathway in a High-Altitude Cerebral Edema Rat Model

High-altitude cerebral edema (HACE) is a disorder caused by low pressure and hypoxia at high altitudes. Nevertheless, as of now, there is still a scarcity of safe and effective prevention and treatment methods. The active component of Ligusticum Chuanxiong, namely Ligustrazine hydrochloride (LH), has shown potential in the prevention and treatment of HACE due to its anti-inflammatory, antioxidant, and neuroprotective effects in nervous system disorders. Consequently, the potential protective effect of LH on HACE and its mechanism still need to be further explored. Prior to modeling, 90 male Sprague-Dawley rats were pretreated with different doses of drugs, including LH (100 mg/kg and 50 mg/kg), dexamethasone (4 mg/kg), and ML385 (30 mg/kg). Subsequently, the pretreated rats were placed in a low-pressure anoxic chamber simulating a plateau environment to establish the rat HACE model. The effects and mechanisms of LH on HACE rats were further elucidated through determination of brain water content, HE staining, ELISA, immunofluorescence, molecular docking, molecular dynamics simulation, western blot, and other techniques. The results showed, first of all, that LH pretreatment can effectively reduce brain water content; down-regulate the expression of AQP4, HIF-1α, and VEGF proteins; and alleviate damage to brain tissue and nerve cells. Secondly, compared with the HACE group, LH pretreatment can significantly reduce MDA levels and increase GSH and SOD levels. Additionally, LH decreased the levels of inflammatory factors IL-1β, IL-6, and TNF-α; reduced total iron content in brain tissue; increased the expression of ferroptosis-related proteins such as SLC7A11, GPX4, and FTH1; and alleviated ferroptosis occurrence. Molecular docking and molecular dynamics simulations show that LH has a strong binding affinity for NRF2 signaling. Western blot analysis further confirmed that LH promotes the translocation of NRF2 from the cytoplasm to the nucleus and activates the NRF2 signaling pathway to exert an antioxidant effect. The NRF2 inhibitor ML385 can reverse the anti-oxidative stress effect of LH and its protective effect on HACE rat brain tissue. In summary, LH may have a protective effect on HACE rats by activating the NRF2 signaling pathway, inhibiting ferroptosis, and resisting oxidative stress.

Multicilia dynamically transduce Shh signaling to regulate choroid plexus functions.

Choroid plexus is a major site for cerebrospinal fluid (CSF) production, characterized by a multiciliated epithelial monolayer that regulates CSF production. We demonstrate that defective choroid plexus ciliogenesis or Intraflagellar transport yields neonatal hydrocephalus, at least in part, due to increased water channel Aqp1 and ion transporter Atp1a2 expression. We demonstrate choroid plexus multicilia as sensory cilia, transducing both canonical and non-canonical Shh signaling. Interestingly, it is the non-canonical Shh signaling that represses Aqp1 and Atp1a2 expression by Smo/Gαi/cAMP pathway. Choroid plexus multicilia exhibit unique ciliary ultrastructure, carrying features of both primary and motile cilia. Unlike most cilia that elongate during maturation, choroid plexus ciliary length decreases during development, causing a decline of Shh signaling intensity in developing choroid plexus, a derepression of Aqp1 and Atp1a2, and ultimately, an increased CSF production. Hence, developmental dynamics of choroid plexus multicilia dampens the Shh signaling intensity to promote CSF production.

Effect of selenium on the dysfunction of rat salivary glands induced by 131I and expression of insulin-like growth factors and aquaporins.

To investigate the effects of selenium on functional and histopathological changes and mRNA expression levels of insulin-like growth factors 1 and 2 (IGF-1 and -2) and aquaporins 4 and 5 (AQP-4 and -5) in 131I-induced damaged rat parotid glands. Rats were divided into three groups: iodotherapy-with-selenium, iodotherapy-only, and control. Rats in the iodotherapy-with-selenium group were intragastrically administered 131I on the first day and selenomethionine through drinking water. Rats in the iodotherapy-only group were only administered 131I. Changes in parotid gland function were evaluated using the functional parameters of salivary gland dynamics imaging pre-experiment and on days 7, 30, and 90 post-treatment. Immunofluorescence and quantitative real-time PCR analyses detected IGF-1, IGF-2, AQP-4, and AQP-5 expression levels in tissues. The gland-to background ratio at a maximum count (G/BGmax), Tmax/Tmin, and Smax values were significantly impacted over time in the iodotherapy-with-selenium group; on day 30, the G/BGmax value was significantly higher than that in the iodotherapy-only group. Histopathological analysis revealed that on days 30 and 90, the iodotherapy-with-selenium group displayed greater parotid gland repair than the iodotherapy-only group. In the iodotherapy-with-selenium group, fluorescence intensity and mRNA levels of AQP-5 increased with the selenium supplementation period, reaching significantly higher levels on days 30 and 90 than in the iodotherapy-only group. Whereas the fluorescence intensity and mRNA levels of IGF-1 in the iodotherapy-with-selenium group were significantly higher on day 7 than on day 30 in the iodotherapy-only group. Selenium may repair 131I-induced tissue and functional damage in rat salivary glands by upregulating AQP-5 and IGF-1 expression.

Zengye decoction regulated the expression of aquaporin in colon tissue of rats with constipation through miR-10a-5p targeting Drd2/AC/cAMP axis.

Slow transit constipation (STC) is a colonic motor disorder characterized by a marked delay in the movement of substances through the colon. Traditional Chinese medicine (TCM) is a treasure trove of natural compounds, which is effective in treating constipation with relatively minor side effects. Zengye decoction (ZYD), a classic herbal formula in TCM, is used for moistening the intestines and relieving constipation. However, the molecular mechanism of ZYD in the treatment of constipation remains unclear. The present study aimed to investigate the effect and molecular mechanism of ZYD on STC. A loperamide-induced rat model and IEC-18 cells were used in vitro and in vivo. We found that ZYD increased the intestinal transit rate and fecal water content of STC rats in a dose-dependent manner. Furthermore, ZYD dose-dependently decreased the expression of Aquaporin (AQP)3 and increased AQP9 expression in the colon tissue of STC rats. Mechanistically, ZYD reduced the level of miR-10a-5p, increased the expression of dopamine receptor D2 (Drd2), and inhibited the activity of adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP) signaling in the colon tissue of STC rats. However, miR-10a-5p overexpression reversed the improvement effect of ZYD on constipation. Moreover, miR-10a-5p targeted Drd2 and enhanced AC/cAMP signaling activation in IEC-18 cells. Also, miR-10a-5p regulated AQP3 and AQP9 expression in IEC-18 cells. Thus, ZYD alleviated constipation and aquaporin expression in STC rats, and its mechanism may be mediated by downregulating miR-10a-5p levels and inhibiting the Drd2/AC/cAMP axis. ZYD may be an efficient therapeutic strategy for constipation.

Tiaogeng decoction improves mild cognitive impairment in menopausal APP/PS1 mice through the ERs/NF-κ b/AQP1 signaling pathway.

People with mild cognitive impairment (MCI) carry a considerable risk of developing dementia. Studies have shown that female sex hormones have long-lasting neuroprotective and anti-aging properties, and the increased risk of MCI and AD is associated with the lack of estrogen during menopause. Previous studies have shown that Tiao Geng Decoction (TGD) may have antioxidant and anti apoptotic properties, which may prevent neurodegenerative diseases. However, whether TGD is effective in improving mild cognitive impairment due to postmenopausal estrogen deficiency and its potential pharmacological mechanisms remain unclear. The aim of this study was to investigate the possible pharmacological mechanisms of TGD in preventing postmenopausal MCI. We utilized RNA-seq technology to screen for differentially expressed genes (DEGs) and enrichment pathways in the hippocampal tissue of different groups of mice. Additionally, we adopted single-cell sequencing technology to study the cell types of Alzheimer's disease (AD) group and Normal Control (NC) group, the differential marker genes of each cell subgroup, and the GO enrichment analysis of each cell type. Both RNA sequencing and single-cell sequencing results showed a significant correlation between TGD and NF-κb pathway in improving mild cognitive impairment in postmenopausal women. The experimental verification results showed that the spatial learning and memory abilities of APP/PS1 model mice were weakened after ovariectomy, and the reproductive cycle on vaginal smears was in the interphase of diestrus. The levels of serum E2, and P-tau181 in mice were significantly down regulated, while the levels of brain tissue homogenate A β 42, IL-1 β, and IL-18 were significantly up-regulated, indicating successful modeling. Combining Western blotting, RT-qPCR, and transmission electron microscopy analyses, it was found that the low estrogen environment induced by oophorectomy can activate the NF-κb signaling pathway, activate the expression of NLRP3 inflammasome and A β secretase BACE1, and induce neuroinflammatory damage in hippocampal astrocytes. These results conform to the modeling characteristics of MCI. After TGD intervention, the spatial learning and memory abilities of MCI mice were significantly improved. The pharmacological validation results indicated that high concentration doses of TGD had a more significant effect on MCI. Subsequently, we used high concentration TGD (0.32 g/ml) as the traditional Chinese medicine group for further validation, protein blotting and RT-qPCR results indicated that TGD can effectively stimulate the secretion of ER α and ER β, inhibit the NF-κb pathway, downregulate BACE1, and inhibit the expression of NLRP3 inflammasome related proteins. In addition, the immunofluorescence results of hippocampal astrocytes showed that TGD can effectively facilitate the expression of AQP1 and significantly lower the sedimentation of A β compared with the model group. Our research suggests that there is a high correlation between a low estrogen environment and the occurrence and development of MCI. TGD may regulate the ERs/NF - κ b/AQP1 signaling pathway, promote estrogen secretion, activate AQP1, reduce A β deposition, reverse MCI neuroinflammatory injury, improve mild cognitive impairment, and prevent the occurrence of AD. This study revealed for the first time that TGD may be a potential new alternative drug for preventing and improving menopausal MCI.

Circadian rhythm disruptions exacerbate inner ear damage in a murine endolymphatic hydrops model.

Meniere's disease (MD) is an inner ear disease characterized by endolymphatic hydrops (EH). Maintaining a regular daily routine is crucial for MD patients. However, the relationship between circadian rhythms and MD remains unclear. Therefore, we investigated the effect of circadian rhythm on endolymphatic hydrops and its underlying mechanisms. Mice with endolymphatic hydrops were subjected to chronic jet lag (CJL) conditions to simulate the MD patients under circadian rhythm disruptions. We assessed whether this disruption would exacerbate inner ear damage with endolymphatic hydrops. RNA-seq of the inner ear and bioinformatic analysis were performed. Then, the expression of PER2, AQP2, AQP4, AQP5, and BDNF were assessed, and the morphological changes were evaluated in the inner ear. Our findings showed circadian rhythm disruption affected the cochlear internal clock genes in the inner ear, particularly in mice with EH. EH mice under CJL conditions exhibited exacerbated hearing impairment and an increased severity of EH. GO enrichment analysis revealed that the regulation of fluid homeostasis and neurotransmitter release at synapses were significantly enriched. Disruption of circadian rhythms disturbed the expression pattern of PER2, reduced BDNF levels, and affected the expression of aquaporins in the cochlea. Moreover, the disruption of circadian rhythm compromised inner hair cell synapses and auditory nerve fibers. This study indicated that disruption of circadian rhythms may exacerbate inner ear damage in endolymphatic hydrops mice by affecting the aquaporins and compromising synapses and auditory nerves in the inner ear. BDNF and PER2 may play a central role in these pathophysiological processes.

The thin descending limb of the loop of Henle originates from proximal tubule cells during mouse kidney development.

The thin descending limb (DTL) of the loop of Henle is crucial for urine concentration, as it facilitates passive water reabsorption. Despite its importance, little is known about how DTL cells form during kidney development. Single-cell RNA sequencing (scRNA-seq) studies have not definitively identified DTL cells in the developing mouse kidney. We assembled a large scRNA-seq dataset by integrating multiple datasets of non-mutant developing mouse kidneys to identify developing DTL cells. To test whether DTL cells originate from proximal tubule (PT) cells, we generated a PT-specific Cre line, Slc34a1eGFPCre , and conducted lineage tracing of PT cells. Additionally, given that the transcription factor Hnf4a directly binds to the Aqp1 gene, we examined whether the loss of Hnf4a affects Aqp1 expression in DTL cells. From our scRNA-seq dataset, we identified a small cluster of cells distinct from both the proximal tubule and the thick ascending limb of the loop of Henle. Those cells exhibited high expression of DTL marker genes, including Aqp1 and Bst1 . Notably, a subset of PT cells also expressed DTL marker genes, suggesting that PT cells may give rise to DTL cells. Using lineage tracing with the Slc34a1eGFPCre line, we found that DTL cells were positive for the Rosa26 reporter, confirming that DTL cells are descendants of PT cells. Furthermore, the loss of Hnf4a, a transcription factor essential for mature PT cell formation, disrupted proper Aqp1 expression in DTL cells, providing additional evidence of a developmental link between PT cells and DTL cells. Our findings shed new light on the developmental origin of DTL cells and highlight the importance of Hnf4a in regulating their formation. Reference single cell RNA-seq dataset of the developing mouse kidney was assembled and used to identify the thin descending limb of the loop of Henle.Lineage analysis of proximal tubules in the mouse kidney shows that proximal tubule cells give rise to the thin descending limb of the loop of Henle. Deletion of Hnf4a disrupts the expression of Aqp1 in the thin descending limb of the loop of Henle, highlighting a developmental link between proximal tubules and the loop of Henle.

The Expression of Thymic AQP7 and Perilipin 1 (PLIN1) in Rats Fed a High-Fructose Diet is Modified by Voluntary Physical Activity

The Expression of Thymic AQP7 and Perilipin 1 (PLIN1) in Rats Fed a High-Fructose Diet is Modified by Voluntary Physical Activity

Genetic and molecular mechanisms of hydrocephalus.

Hydrocephalus is a neurological condition caused by aberrant circulation and/or obstructed cerebrospinal fluid (CSF) flow after cerebral ventricle abnormal dilatation. In the past 50 years, the diagnosis and treatment of hydrocephalus have remained understudied and underreported, and little progress has been made with respect to prevention or treatment. Further research on the pathogenesis of hydrocephalus is essential for developing new diagnostic, preventive, and therapeutic strategies. Various genetic and molecular abnormalities contribute to the mechanisms of hydrocephalus, including gene deletions or mutations, the activation of cellular inflammatory signaling pathways, alterations in water channel proteins, and disruptions in iron metabolism. Several studies have demonstrated that modulating the expression of key proteins, including TGF-β, VEGF, Wnt, AQP, NF-κB, and NKCC, can significantly influence the onset and progression of hydrocephalus. This review summarizes and discusses key mechanisms that may be involved in the pathogenesis of hydrocephalus at both the genetic and molecular levels. While obstructive hydrocephalus can often be addressed by removing the obstruction, most cases require treatment strategies that involve merely slowing disease progression by correcting CSF circulation patterns. There have been few new research breakthroughs in the prevention and treatment of hydrocephalus.

NOTCH3 Mutation Causes Glymphatic Impairment and Promotes Brain Senescence in CADASIL.

The aim of this study is to investigate the role of glymphatic function of cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL), the most common monogenic small vessel disease caused by NOTCH3 mutation, and to explore potential therapeutic strategies to improve glymphatic function. We assessed glymphatic influx and efflux function in CADASIL mouse models (Notch3R170C) and correlated these findings with brain atrophy in CADASIL patients. We also investigated the underlying mechanisms of glymphatic impairment, focusing the expression of AQP4 in astrocytic endfeet. CADASIL mouse exhibited both impaired glymphatic influx and efflux, which impedes waste clearance and promotes brain senescence. In accordance, brain atrophy in CADASIL patients is associated with perivascular space enlargement, indicating that glymphatic impairment contributes to advanced brain senescence in CADASIL. The glymphatic malfunction in CADASIL is attributed to diminished AQP4 expression in astrocytic endfeet, which is the core mediator of glymphatic activity. Mechanistically, AQP4 expression is regulated by NOTCH3-RUNX1-CMYB signaling. Reinforcing AQP4 expression in astrocytes by AAV-based therapy resumes the glymphatic functions in CADASIL mice, which further prevents brain senescence. We propose that to improve glymphatic function by reinforcing AQP4 expression is a promising therapeutic strategy in CADASIL.

Aquaporin-2 in the early stages of the adenine-induced chronic kidney disease model.

Chronic kidney disease (CKD) is one of the leading health problems in the world. It is silent in the early stages and gradually progresses, inducing renal physiological and structural alterations. Moreover, CKD is associated with impaired life quality, increased risk for cardiovascular diseases, and reduced life expectancy. Different CKD animal models differ in underlying etiology, time of onset, and associated diseases. The 0.25% adenine diet induces progressive kidney damage, constituting an adequate model mimicking human CKD. Vasopressin (VP) was postulated as a mediator of CKD, mainly acting through its V2 receptors. However, the molecular mechanisms involved in the pathogenesis of this condition and its progression still are not entirely understood. This study aimed to evaluate if AQP2 expression is altered in an adenine-induced model of CKD in rats at early stages of development (two weeks) and to assess a potential beneficial effect of Tolvaptan (a V2 receptor antagonist) treatment. We showed an increased renal medullary AQP2 expression at two weeks of adenine administration. This increase was mainly cytoplasmic, explaining the increased urinary volume of CKD rats and suggesting a possible non-canonical role for AQP2. In addition, Tolvaptan effectively inhibited the V2 receptor in both control and CKD rats, decreasing AQP2 expression and increasing diuresis. Moreover, Tolvaptan slightly reduced BUN and plasma creatinine. On the other hand, the renal alterations induced by adenine in CKD rats were not prevented by Tolvaptan.

Relationship between water loss and water status, osmotic substances, and AQP expression in Ponkan (Citrus reticulata Blanco) fruit during storage

Relationship between water loss and water status, osmotic substances, and AQP expression in Ponkan (Citrus reticulata Blanco) fruit during storage

Huashi baidu granule alleviates inflammation and lung edema by suppressing the NLRP3/caspase-1/GSDMD-N pathway and promoting fluid clearance in a porcine reproductive and respiratory syndrome (PRRS) model.

Huashi Baidu Granule (HSBDG), a traditional Chinese medicine (TCM), is used for treating coronavirus disease 2019 (COVID-19). Porcine reproductive and respiratory syndrome (PRRS) is considered the "COVID-19" for swine. According to the TCM theory, "dampness" is the main pathogenic factor in COVID-19 and PRRS, and "Huashi" means that this formula is good at removing "dampness". Studies have demonstrated that HSBDG's effect in COVID-19; but the mechanism of removing "dampness" remains elusive. We aimed to assess the effect of HSBDG on PRRS, and elucidate its potential mechanism in removing "dampness". We established a PRRS-virus (PRRSV)-infected Marc-145cells model, and performed qRT-PCR, Western blot analysis, and indirect immunofluorescence assay to examine the anti-PRRSV effects of HSBDG in vitro. PRRSV-infected pig model was established and used to investigate HSBDG's effect in PRRS and explore underlying mechanisms in removing "dampness" using ELISA and immunohistochemistry assay methods. HSBDG exhibited anti-PRRSV activity and suppressed the viral replication and release phases. HSBDG treatment alleviated PRRS, lowered rectal temperature, reduced histopathological changes and viral load in lung tissues, and ameliorated organ lesions. Moreover, IL-1β, IL-6, IL-8, and TNF-α expressions were decreased in lung tissues. Mechanistically, HSBDG inhibited the NLRP3/Caspase-1/GSDMD-N pathway to reduce the inflammatory response and upregulated AQP1, AQP5, α-ENaC, and Na-K-ATPase expressions to promote lung fluid clearance. HSBDG exerted anti-PRRSV effects and could attenuate PRRS. HSBDG potentially removes "dampness" by attenuating inflammation by suppressing the NLRP3/Caspase-1/GSDMD-N pathway and inhibiting pulmonary edema by upregulating the expression of AQP1, AQP5, α-ENaC, and Na-K-ATPase.

Carvacrol attenuates varicocele-induced infertility in rats.

Carvacrol is a common ingredient in the pharmaceutical, cosmetic, and perfume industries. It possesses various pharmaceutical properties including pain relief, anti-cell death, antioxidant, anti-cancer, and anti-inflammatory effects. We investigated the protective impact of carvacrol on infertility caused by varicocele in rats. The animals were assigned to nine groups randomly: control, sham-operated, carvacrol alone at 10, 20, and 40 mg/kg b.w./day, varicocele-induced control, and varicocele-induced rats treated with carvacrol. After thirty days of treatment, the serum was collected to evaluate testosterone levels, and left epididymal sperm samples were obtained to assess sperm quality. Additionally, the left testis was removed for biochemical and histopathological evaluation. The findings demonstrated that carvacrol administration (20 and 40 mg/kg) notably improved sperm quality in rats with varicocele. Furthermore, carvacrol treatment (20 and 40 mg/kg) increased antioxidant levels, reduced MDA levels, decreased AQP9 expression in testicular tissue, and improved testicular tissue structure. Hence, carvacrol (20 and 40 mg/kg) may serve as a therapeutic agent for male reproductive system disorders, particularly varicocele-related infertility, due to its antioxidant properties and protective effects on testicular function.

Investigating “Xinshuixiao” Serum's Impact on dDAVP-Induced AQP2 Expression and Mechanisms in IMCD3 Cells

Objective To investigate the impact of “Xinshuixiao” drug-containing serum on dDAVP-induced AQP2 expression in IMCD3 cells and to preliminarily explore its underlying mechanisms. Methods Rats were orally administered with “Xinshuixiao granules” containing medicinal compounds. The CCK-8 assay was employed to determine the appropriate drug serum concentration and its effect on IMCD3 cell viability. Additionally, we assessed the influence of “Xinshuixiao” drug-containing serum on IMCD3 cell activity following dDAVP intervention. Cells were divided into blank, model, low, medium, and high-dose “Xinshuixiao” drug serum groups, as well as a Tolvaptan group. After 24 h of drug treatment, ELISA was used to measure the levels of arginine vasopressin (AVP), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in the cell supernatant. Western blotting was employed to evaluate AQP2 protein expression, and real-time polymerase chain reaction (Real-time PCR) was used to assess AQP2 mRNA expression levels. Results In comparison to the blank group, the model group exhibited elevated expression of AVP, cAMP, PKA ( P<0.05), as well as increased AQP2 mRNA and protein expression ( P<0.05). When compared to the model group, all treatment groups displayed varying degrees of reductions in AVP, cAMP, and PKA expression ( P<0.05), along with decreased AQP2 mRNA and protein expression, with statistically significant differences ( P<0.05). Conclusion “Xinshuixiao” drug-containing serum exerts an inhibitory effect on the overexpression of AQP2 induced by dDAVP in IMCD3 cells, which may be associated with its suppression of the cAMP/PKA signaling pathway.