Search

Alterations in genes specifically expressed in the pancreas have been associated with chronic pancreatitis (CP). A significant percentage of patients with non-alcoholic CP, however, do not have mutations in known risk genes, suggesting the existence of further susceptibility genes. Four aquaporins are expressed in the exocrine pancreas: AQP1, AQP5, AQP8 and AQP12, the latter being found exclusively in this organ. Therefore, we investigated the two AQP12 genes, AQP12A and AQP12B, in CP patients.We analyzed all exons and adjacent intronic regions of AQP12A and AQP12B in 292 German patients with non-alcoholic CP and 143 control subjects by direct DNA sequencing.In total, we discovered 41 non-synonymous changes, three of which were nonsense variants. Genotype and allele frequencies of these variants did not differ significantly between patients and controls (all p-values0.05). Remarkably, we found a common nonsense variant in AQP12B, p.S152Tfs∗24, with an allele frequency of 15.7% in controls, including 2.8% homozygous subjects. This finding suggests that AQP12B is physiologically dispensable for normal pancreatic function.Our results suggest that genetic alterations in AQP12A and AQP12B do not predispose to the development of non-alcoholic CP.

Cadmium (Cd) is a toxicant metal that risks human and animal health. Nowadays, the vital role of Aquaporin-4 (AQP-4) in brain and gut cell permeability has gathered too much attention to protecting against heavy metals. Studies have shown that heavy metals can harm the body due to oxidative stress. Probiotics are known for their health-beneficial effects and establish as dietary adjuncts mainly for their antioxidant properties. This study investigated the impact of a novel probiotic combination including Lactobacillus casei IBRC-M10783, Lactobacillus rhamnosus IBRC-M10782, and Lactobacillus helveticus TG-34 on the AQP-4 gene expression in CdCl2-induced Wistar rats. Rats were divided into three groups and received a specific dose of CdCl2 or probiotics. The AQP-4 expression level had estimated by Real-Time PCR in both the intestine and brain. These results showed a significant reduction in AQP-4 gene expression in the probiotic treatment group compared to the CdCl2 control group in the intestine and brain for the first time. Our research showed that consuming a probiotic mixture of L. casei, L. rhamnosus, and L. helveticus can reduce the expression of the aquaporin-4 gene in the brain and intestine of rats exposed to Cadmium, which can be promising in the field of aquaporin-4 regulation.

To evaluate serum anti-aquaporin antibodies profile, to measure serum levels of cell-cell adhesion molecules as potential markers of blood-brain barrier (BBB) permeability, and to assess their relationship in neuromyelitis optica spectrum disorders (NMOsd) and multiple sclerosis (MS).Serum levels of cell-cell adhesion molecules could provide information about BBB disruption in demyelinating diseases of the central nervous system. Improved knowledge about differences in their profile in NMOsd and MS patients, as well as about their relationship with antibody serostatus, would facilitate early and accurate diagnosis.Sera from 20 NMOsd and 59 MS patients were collected and assessed for anti-aquaporin 4 antibodies (AQP4-IgG) and antibodies against myelin oligodendrocyte glycoprotein (MOG-Ab) using an indirect immunofluorescence test (IIFT). Anti-aquaporin 1 antibodies (AQP1-Ab), vascular endothelial growth factor (VEGF), and vascular endothelial cadherin (VE-Cadherin) levels were assessed using commercial enzyme-linked immunosorbent assay (ELISA) kits. For occludin (OCLN) and claudin-5 (CLDN5) serum levels, we employed home-made ELISAs elaborated in the Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Poland.AQP4-IgG appeared only in 6/20 NMOsd patients who were all originally AQP4-IgG seropositive. All MS and NMOsd patients were seronegative for MOG-Ab. Patients with MS had higher AQP1-Ab levels than those with NMOsd (median 782.32 vs. 203.16 pg/mL; p0.001). CLND5 levels were significantly higher in MS than in NMOsd patients (median 1.65 vs. 1.00 ng/mL; p = 0.004). No statistically significant differences between MS and NMOsd were found for OCLN, VEGF and VE-Cadherin serum levels. In MS, AQ1-Ab levels were significantly lower in MS patients treated with immunomodulatory drugs vs. the treatment-naive (median 712.46 pg/mL vs. 942.73 pg/mL, respectively). There was a positive correlation between CLDN5 and OCLN in both the MS and the NMOsd groups.There is a different BBB disruption profile in MS and NMOsd, reflected by significantly higher CLDN5 and AQP1-Ab levels in MS samples. AQP1-Ab can be considered as a promising indicator of BBB disruption possibly associated with astrocytopathy.

The expression of various isoforms of aquaporins (AQPs) in different tissues and organs of the body makes it a viable candidate for being responsible for maintaining cell stability and integrity as their involvement has been well documented in a number of pathophysiological conditions of the human body. Any alteration in the cellular environment brought about by these AQPs creates severe downstream effects like changes in cellular osmolality, volume, ionic composition, signaling pathways and even in the levels of intracellular second messengers and, as such, facilitates the occurrence of diseases like cancer. The altered equilibrium of water, extracellular ions and amino acid neurotransmitters caused by neuronal destruction and oxidative stress in neurodegenerative diseases proposed the role of these AQPs in these diseased conditions as well. The association of AQPs in a variety of inflammatory processes like lung injury, brain edema, neuromyelitis optica, and colitis as manifested through their dysregulation both in animal and human diseases is truly an eye opener for their role in protection and reaction to various noxious stimuli including bacterial infection. Renal diseases like nephrogenic diabetes inspidus, autosomal dominant polycystic kidney disease and acute kidney injury are some of the pathophysiological conditions related to malfunctioning of aquaporins. Besides, the malfunctioning of aquaglyceroporins like AQP7 and AQP9 makes them responsible for disorders like obesity, nonalcoholic fatty liver disease and non-alcoholic steatohepatitis. In this review article, we present our current understanding of the role of AQPs in the causation of these metabolic disorders and how targeting them holds promising therapeutic potential for most of these diseases like cancer, renal diseases and even cardiovascular disorders.

The mechanism of idiopathic oligohydramnios is still uncertain, and there is no effective and targeted treatment for it. Placental aquaporins (AQPs) were associated with idiopathic oligohydramnios. This study aimed to investigate the effect of tanshinone IIA on amniotic fluid volume (AFV) and its underlying molecular mechanisms related to placental AQPs (AQP1, AQP3, AQP8, AQP9). Results showed that compared with the women with normal AFV, placental AQP1, AQP3, AQP8, and AQP9 protein expressions were decreased in women with idiopathic oligohydramnios. Immunohistochemistry revealed localization of AQP1, AQP3, AQP8, and AQP9 mainly in trophoblast cells within labyrinth zone of mouse placenta. Also, AQP1 was located in fetal vascular endothelial cells. Pregnant mice were administered with tanshinone IIA (10 mg/kg or 50 mg/kg, n = 8, respectively) or vehicle (n = 8) from 9.5 to 18.5 gestational day (GD). Tanshinone IIA markedly increased the AFV in pregnant mice, without the effects on embryo numbers per litter, atrophic embryo rate, fetal weight, and placental weight, as well as increased the expressions of AQPs and inhibited the activity of GSK-3β in mice placenta. In JEG-3 cells, tanshinone IIA downregulated AQP1, AQP3, AQP8, AQP9 expressions and inhibited the activity of GSK-3β. Activating GSK-3β with MK-2206 eliminated these alterations. Thus, tanshinone IIA could increase AFV in pregnant mice, possibly through downregulating placental AQP1, AQP3, AQP8, and AQP9 expression via inhibiting the activity of GSK-3β. Tanshinone IIA may be optional for the treatment of idiopathic oligohydramnios.

Objective This study aimed to detect aquaporin-9 (AQP9) concentrations in the serum of patients with preterm premature rupture of membranes (PPROM) and compare them with the healthy control group with intact membranes.Material and methods We conducted this prospective case-control study from March 2021 to August 2021. Of the 80 pregnant patients included in the study, we enrolled 42 singleton pregnant patients with PPROM as the study group and 43 healthy gestational age-, and body mass index (BMI)-matched healthy pregnant women with intact fetal membranes as the control group. We compared demographic and clinical characteristics, complete blood count and biochemical parameters, and serum AQP9 concentrations of the participants. We constructed an ROC curve to illustrate the sensitivity and specificity performance characteristics of AQP9 and calculated a cutoff value by using the Youden index.Results Maternal serum AQP-9 concentrations were significantly higher in patients with PPROM (804.46±195.63 pg/mL) compared to the healthy pregnant women in the control group (505.97±68.89 pg/mL, pConclusion Maternal serum AQP9 concentrations were significantly higher in PPROM patients than healthy pregnant women with an intact membrane. We suggest that AQP9 might be an essential biomarker of the inflammatory process and energy homeostasis in PPROM.

Purpose. Diabetic macular edema (DME) is a major cause of vision loss in patients with diabetic retinopathy; this study is aimed at comparing the expression of aquaporins (AQPs) on the inner limiting membranes (ILMs) of various vitreoretinal diseases and investigating the role of aquaporins expressed on the ILMs in mediating the occurrence of DME. Methods. The whole-mounted ILM specimens surgically excised from patients with various vitreoretinal diseases (idiopathic macular hole, myopic traction maculopathy, and diabetic retinopathy) were analyzed by immunohistochemistry (IHC). The distribution and morphology of AQP4, AQP7, and AQP11 on the ILMs were correlated with immunohistochemical staining characteristics. Moreover, immunofluorescence of AQP4 was performed on the ILM specimens of the patient in four groups: the control group, negative control group, no DME group, and DME group. The immunofluorescence intensity value of AQP4 was measured using ImageJ. The difference between the four groups and the correction between the immunofluorescence value and central foveal thickness (CFT) were analyzed. Results. In IHC sections, the expression of AQP4, AQP7, and AQP11 on ILMs of diabetic retinopathy (DR) with macular edema, respectively, seemed to be more abundant than in the idiopathic macular hole (iMH) and myopic traction maculopathy (MTM). Moreover, markedly higher fluorescence intensity of AQP4 of ILMs was determined in the DME group ( 51.05 ± 5.67 ) versus the other three groups ( P < 0.001 ). A marked positive association was identified between the fluorescence intensity of AQP4 and CFT ( r = 0.758 ; P = 0.011 ). Conclusions. AQP4, AQP7, and AQP11 can be expressed on human ILM in vivo. The increased expression of AQPs on the ILMs of DR may be associated with the occurrence of DME. Moreover, the degree of DME may be positively correlated with the expression of AQP4 on the ILMs.

Background Cerebral malaria (CM) is associated with sequestration of parasitized red blood cells (PRBCs) in the capillaries. Often, the association of CM with cerebral oedema is related with high mortality rate. Morphological changes of the choroid plexus (CP) and caspase-3 expression in CM have not been reported. In addition, limited knowledge is known regarding the role of aquaporin (AQP)-1 in CM. The present study evaluated changes in the CP, explored apoptotic changes and AQP-1 expression in CP epithelial cells (CPECs) in fatal CM patients. Methods CP from fatal Plasmodium falciparum malaria patients (5 non-CM [NCM], 16 CM) were retrieved and prepared for histopathological evaluation. Caspase-3 and AQP-1 expressions in CPECs were investigated by immunohistochemistry. Results Histologically, apoptotic changes in CPECs were significantly observed in the CM group compared with the NCM and normal control (NC) groups (p p rs = − 0.450, p = 0.024) was documented between caspase-3 expression in the nuclei of CPECs and AQP-1. Conclusions Apoptotic changes and altered AQP-1 expression may contribute to CPEC dysfunction and subsequently reduce cerebrospinal fluid production, affecting the water homeostasis in the brains of patients with CM.

We explored the contribution of each aquaporin (AQP) expressed in human amnion in the transcellular water flux across the human amnion. Human amnion was placed between two lucite chambers and net water transport (Jw) was recorded by applying a hydrostatic (7 cm H

Aquaporin (AQP) water channels facilitate water transport across cellular membranes and are essential in regulation of body water balance. Moreover, several AQPs are overexpressed or ectopically expressed in breast cancer. Interestingly, several in vitro studies have suggested that AQPs can affect the response to conventional anticancer chemotherapies. Therefore, we took a systematic approach to test how AQP1, AQP3 and AQP5, which are often over-/ectopically expressed in breast cancer, affect total viability of 3-dimensional (3D) breast cancer cell spheroids when treated with the conventional anticancer chemotherapies Cisplatin, 5-Fluorouracil (5-FU) and Doxorubicin, a Combination of the three drugs as well as the Combination plus the Ras inhibitor Salirasib. Total viability of spheroids overexpressing AQP1 were decreased by all treatments except for 5-FU, which increased total viability by 20% compared to DMSO treated controls. All treatments reduced viability of spheroids overexpressing AQP3. In contrast, only Doxorubicin, Combination and Combination + Salirasib reduced total viability of spheroids overexpressing AQP5. Thus, this study supports a significant role of AQPs in the response to conventional chemotherapies. Evaluating the role of individual proteins that contribute to resistance to chemotherapies is essential in advancing personalized medicine in breast carcinomas. Aquaporin (AQP) water channels facilitate water transport across cellular membranes and are essential in regulation of body water balance. Moreover, several AQPs are overexpressed or ectopically expressed in breast cancer. Interestingly, several in vitro studies have suggested that AQPs can affect the response to conventional anticancer chemotherapies. Therefore, we took a systematic approach to test how AQP1, AQP3 and AQP5, which are often over-/ectopically expressed in breast cancer, affect total viability of 3-dimensional (3D) breast cancer cell spheroids when treated with the conventional anticancer chemotherapies Cisplatin, 5-Fluorouracil (5-FU) and Doxorubicin, a Combination of the three drugs as well as the Combination plus the Ras inhibitor Salirasib. Total viability of spheroids overexpressing AQP1 were decreased by all treatments except for 5-FU, which increased total viability by 20% compared to DMSO treated controls. All treatments reduced viability of spheroids overexpressing AQP3. In contrast, only Doxorubicin, Combination and Combination + Salirasib reduced total viability of spheroids overexpressing AQP5. Thus, this study supports a significant role of AQPs in the response to conventional chemotherapies. Evaluating the role of individual proteins that contribute to resistance to chemotherapies is essential in advancing personalized medicine in breast carcinomas.

BACKGROUND: Role of aquaporin-8 (AQP8) in cervical cancer has not been fully elucidated. OBJECTIVE: We aim to explore the impacts of AQP8 on viability, apoptosis and metastasis in cervical cancer cells. METHODS: AQP8 protein expression in cervical carcinoma specimens and cell lines was detected by IHC and western blot analysis. Lentivirus-mediated transfection was used to upregulate and knockdown AQP8 in cells. Cell viability and apoptosis were assessed by CCK-8 and flow cytometry assays, respectively. Transwell experiments were conducted to investigate cell invasive and migratory capabilities. EMT-related markers were detected by western blot analysis. RESULTS: A strong positive of AQP8 protein expression was observed in cervical cancer tissues. Western blot analysis confirmed overexpression and knockdown of AQP8 in SiHa cells. AQP8-overexpressed SiHa cells displayed an enhanced viability, reduced apoptotic rate, increased invasive and migratory abilities. Knockdown of AQP8 inhibited the viability, promoted the apoptosis, and suppressed invasion and migration. Furthermore, AQP8 overexpression significantly upregulated vimentin and N-cadherin, and downregulated E-cadherin, which were reversed by AQP8 knockdown. CONCLUSIONS: AQP8 increases viability, inhibits apoptosis, and facilitates metastasis in SiHa cells. This may be associated with EMT-related markers regulated by AQP8. AQP8 could serve as a potential marker for cervical cancer progression.

Despite aquaporin water channels (AQPs) play a critical role in maintaining water homeostasis in female reproductive tract and prompt a gradual increase in water content in cervical edema as pregnancy progressed, their relationship with macrophage infiltration and collagen content in human cervical remodeling need to be further investigated. This is the first study to examine the expression and localization of AQP3, AQP4, AQP5, AQP8, and macrophages simultaneously in human cervical ripening. The immunoreactivity of these AQPs was 2.6 to 6-fold higher on gestational weeks 26 (GD26W) than that on GD6W and GD15W, but AQP4 expression on GD39W dropped a similar extent on GD15W, other AQPs continued to rise on GD39W. The AQP3, AQP4, and AQP5 intensity seemed more abundant in cervical stroma than in the perivascular area on GD26W; the distribution of AQP3, AQP5, and AQP8 in cervical stroma was equivalent to that in the perivascular area on GD39W. Macrophage numbers were 1.7-fold higher in subepithelium region and 3.0-fold higher in center area on GD26W than that on GD15W; such numbers remained elevated on GD39W. The electron micrographs showed that cervical extensibility increased significantly on GD26W and GD39W accompanied with increased macrophage infiltration, cervical water content, and much more space among collagen fibers. These findings suggest that the upregulation of AQPs expression in human cervix is closely related to enhanced macrophage infiltration during pregnancy; there may be a positive feedback mechanism between them to lead the increase of water content and the degradation of collagen.

Aquaporins are water channel proteins facilitating passive transport of water across cellular membranes. Aquaporins are over- or ectopically expressed in a multitude of cancers, including pancreatic ductal adenocarcinoma, which is a highly aggressive cancer with low survival rate. Evidence suggests that aquaporins can affect multiple cellular processes involved in cancer development and progression including epithelial-mesenchymal transition, cellular migration, cell proliferation, invasion, and cellular adhesions. In pancreatic ductal adenocarcinoma, aquaporin-1, aquaporin-3, and aquaporin-5 are overexpressed and have been associated with metastatic processes and poor survival. Thus, aquaporin expression has been suggested as diagnostic markers and therapeutic targets in pancreatic ductal adenocarcinoma.

This study aimed to examine maternal serum aquaporin 9 levels in pregnant women with gestational diabetes mellitus and to compare them with non-diabetic pregnant women.Forty-one pregnant women between 37 and 39 weeks of gestation complicated with gestational diabetes mellitus and 39 non-diabetic pregnant women at similar gestational weeks without additional obstetric complications were included in this cross-sectional study. Maternal serum aquaporin 9 levels and leptin levels of the cases were measured.Maternal serum leptin and aquaporin 9 levels in pregnant women with GDM were found to be significantly higher than in the control group (The increased aquaporin 9 levels detected in cases with gestational diabetes mellitus might be a marker of the poor maternal metabolic environment specific to diabetes and might contribute to the pathophysiology of gestational diabetes.

Bile secretion by hepatocytes is an osmotic process. The output of bile salts and other organic anions (e.g. glutathione), through the bile salt transporter BSEP/ABCB11 and the organic anion transporter MRP2/ABCC2, respectively, are considered to be the major osmotic driving forces for water secretion into bile canaliculi mainly via aquaporin-8 (AQP8) channels. The down-regulated canalicular expression of these key solute transporters and AQP8 would be a primary event in the establishment of hepatocellular cholestasis. Recent studies in animal models of hepatocellular cholestasis show that the hepatic delivery of AdhAQP1, an adenovector encoding for the archetypical water channel human aquaporin-1 (hAQP1), improves bile secretion and restores to normal the elevated serum bile salt levels. AdhAQP1-transduced hepatocytes show that the canalicularly-expressed hAQP1 not only enhances osmotic membrane water permeability but also induces the transport activities of BSEP/ABCB11 and MRP2/ABCC2 by redistribution in canalicular cholesterol-rich microdomains likely through interactions with the cholesterol-binding protein caveolin-1. Thus, the hepatic gene transfer of hAQP1 improves the bile secretory failure in hepatocellular cholestasis by increasing both biliary output and choleretic efficiency of key osmotic solutes, such as, bile salts and glutathione. The study of hepatocyte aquaporins has provided new insights into the mechanisms of bile formation and cholestasis, and may lead to innovative treatments for cholestatic liver diseases.

Aquaporins (AQPs) are transmembrane water channels and some of them are permeable in addition to water to other small solutes including hydrogen peroxide. The sperm cells of mammals and fishes express different AQPs, although there is no agreement in the literature on their localization. In humans, AQP3 and AQP11 are expressed mainly in the tail, AQP7 in the head and AQP8 in the midpiece. Thanks to the results of experiments with KO mice and to data obtained by comparing sub-fertile patients with normospermic subjects, the importance of AQPs for the normal functioning of sperms to ensure normal fertility emerged. AQP3, AQP7 and AQP11 appeared involved in the sperm volume regulation, a key role for fertility because osmoadaptation protect the sperm against a swelling and tail bending that could affect sperm motility. AQP8 seems to have a fundamental role in regulating the elimination of hydrogen peroxide, the most abundant reactive oxygen species (ROS), and therefore in the response to oxidative stress. In this review, the human AQPs expression, their localization and functions, as well as their relevance in normal fertility are discussed. To understand better the AQPs role in human sperm functionality, the results of studies obtained in other animal species were also considered.

The purpose of this study was to determine whether rodent lacrimal glands (LGs) represent a suitable surrogate for human tissue in bio-engineering research, we undertook a meticulous histological and histochemical comparison of these two tissues.Histological techniques and immunohistochemistry were used to compare the structure of adult human and rat LG tissues and the expression of key functional tissue elements.Compared with humans, the rat LG is comprised of much more densely packed acini which are devoid of an obvious central lumen. Myoepithelial, fibroblasts, dendritic cells, T cells, and putative progenitor cells are present in both tissues. However, human LG is replete with epithelium expressing cytokeratins 8 and 18, whereas rat LG epithelium does not express cytokeratin 8. Furthermore, human LG expresses aquaporins (AQPs) 1, 3, and 5, whereas rat LG expresses AQPs 1, 4, and 5. Additionally, mast cells were identified in the rat but not the human LGs and large numbers of plasma cells were detected in the human LGs but only limited numbers were present in the rat LGs.The cellular composition of the human and rat LGs is similar, although there is a marked difference in the actual histo-architectural arrangement of the tissue. Further variances in the epithelial cytokeratin profile, in tissue expression of AQPs and in mast cell and plasma cell infiltration, may prove significant.The rat LG can serve as a useful surrogate for the human equivalent, but there exist specific tissue differences meaning that caution must be observed when translating results to patients.

Congenital cataracts (CCs) have significant genotypic and phenotypic heterogeneity. The major intrinsic protein (MIP) gene, one of the causative genes of CCs, plays a vital role in maintaining the homeostasis and transparency of the lens. In this study, we identified a unique phenotype of anterior umbilication of the lens in a four-generation pedigree with CCs. All patients in the observed family had nystagmus, nuclear cataracts, and elongated axial lengths compared with their healthy counterparts except for patient I:2, whose axial length was unavailable, and patientII:4, who had total cataracts. We confirmed, using Sanger sequencing based on whole-exon sequencing (WES) data, that all patients carried a heterozygous variant NM_012064.4:c.97C > T (NP_036196.1:p.R33C) in their MIP gene. To our knowledge, 29 variants of the human MIP gene and the relative phenotypes associated with CCs have been identified. Nevertheless, this is the first report on the anterior umbilication of the lens with nuclear or total opacity caused by the c.97C > T (p.R33C) variant in the MIP gene. These results also provide evidence that the elongated axial length might be associated with this variant. This study further confirms the phenotypic heterogeneity of CCs.

Aquaporins (AQPs) are a family of membrane water channels that facilitate the passive transport of water across the plasma membrane of cells in response to osmotic gradients created by the active transport of solutes. Water-selective AQPs are involved in tumor angiogenesis, invasion, metastasis and growth. However, the polytype expression patterns and prognostic values of eleven AQPs in clear cell Renal Cell Cancer (ccRCC) have yet to be filled. We preliminarily investigated the transcriptional expression, survival data and immune infiltration of AQPs in patients with renal cell cancer via the Oncomine database, Kaplan-Meier Plotter, UALCAN cancer database, and cBioPortal databases. The ethical approval was waived by the local ethics committee of Peking University People's Hospital for the natural feature of mine into databases. The mRNA expression of AQP1/2/3/4/5/6/7/11 was significantly decreased in ccRCC patients. Meanwhile, MIP and AQP1/2/4/6/7/8/9/11 are notably related to the clinical stage or pathological grade of ccRCC. Lower levels of AQP1/3/4/5/7/10 expression were related to worse overall survival (OS) in patients diagnosed with ccRCC. The AQP mutation rate was 25% in ccRCC patients, but genetic alterations in AQPs were unlikely to be associated with OS and disease free survival in ccRCC patients. In addition, the expression of AQP1, AQP3, AQP4 and AQP10 was positively correlated with immune cells, and the expression of AQP6, AQP7 and AQP11 was negatively correlated with immune cells. AQP9 had a strong and significantly positive correlation with multiple immune cells. Abnormal expression of AQPs in ccRCC indicated the prognosis and immunomodulatory state of ccRCC. Further study needs to be performed to explore AQPs as new biomarkers for ccRCC.

Glycerol is seen in biological systems as an intermediate in lipid metabolism. In recent years, glycerol has been reported to act as a chemical chaperone to correct the conformation of proteins. Here, we investigate the role of glycerol in galectin-7 (Gal-7). The thermal shift and CD assays showed that the thermal stability of Gal-7 increased with glycerol concentration but with little secondary structure changes induced by glycerol. In addition, glycerol can inhibit Gal-7-mediated erythrocyte agglutination. We also solved the crystal structures of human Gal-7 in complex with glycerol in two different conditions. Glycerol binds at the carbohydrate-recognition binding sites of Gal-7, which indicates glycerol as a small ligand for Gal-7. Surprisingly, glycerol can bind a new pocket near the N-terminus of Gal-7, which can greatly reduce the flexibility and improve the stability of this region. Moreover, overexpression of Gal-7 decreased the intracellular triglyceride levels and increased mRNA expression of aquaporin-3 (AQP-3) when HeLa cells were incubated with glycerol. These findings indicate that Gal-7 might regulate glycerol metabolism. Overall, our results on human Gal-7 raise the perspective to systematically explore this so far unrecognized phenomenon for Gal-7 in glycerol metabolism.

The paper aimed at exploring the correlation between CT findings of diffuse axonal injury and the expression of neuronal aquaporin in patients with craniocerebral injury.150 patients with diffuse axonal injury diagnosed by CT and 50 healthy physical examinators were selected as the study objects. According to the craniocerebral CT and GCS scale scores, the patients were divided into DAI light group, medium group, and heavy group. The general conditions of patients were observed and recorded, and the brain pathological morphology, craniocerebral edema and CT imaging results of the patients in each group were compared. Changes in serum and brain AQP-4 levels were detected by RT-PCR and Western blot, and the correlation between CT manifestations of DAI and the expression of neuronal aquaporin was investigated.The results of DAI's pathological morphology, cerebral edema and CT imaging showed that the brain tissue of each group of DAI had a certain degree of injury. With the increase of the injury degree, the degree of edema and the number of axonal injuries sharply increased, and the difference was significant (p-value0.05). Therefore, CT could be used as an effective basis for the rapid and efficient diagnosis of DAI. RT-PCR, Western blot and Spearman correlation analysis showed that the levels of AQP-4 in the serum and brain tissue of DAI patients were significantly increased. With the increase of the degree of diffuse axonal injury, the expression level of AQP-4 was further increased, and the difference was significant (p-value0. 05). The CT manifestations of patients in each group were positively correlated with the expression level of AQP-4 protein.AQP-4 can be used as an important molecular index to judge the condition and prognosis of DAI, providing a new non-invasive detection method for the clinical diagnosis and treatment of DAI, which has high clinical application value.

Aquaporin-9 (AQP9) is a facilitator of glycerol and other small neutral solute transmembrane diffusion. Identification of specific inhibitors for aquaporin family proteins has been difficult, due to high sequence similarity between the 13 human isoforms, and due to the limited channel surface areas that permit inhibitor binding. The few AQP9 inhibitor molecules described to date were not suitable for in vivo experiments. We now describe the characterization of a new small molecule AQP9 inhibitor, RG100204 in cell-based calcein-quenching assays, and by stopped-flow light-scattering recordings of AQP9 permeability in proteoliposomes. Moreover, we investigated the effects of RG100204 on glycerol metabolism in mice. In cell-based assays, RG100204 blocked AQP9 water permeability and glycerol permeability with similar, high potency (~5 × 10

BACKGROUND & AIMS Patient-derived human induced pluripotent stem cells (hiPSCs) differentiated into hepatocytes (hiPSC-Heps) have facilitated the study of rare genetic liver diseases. Here, we aimed to establish an in vitro liver disease model of the urea cycle disorder ornithine transcarbamylase deficiency (OTCD) using patient-derived hiPSC-Heps. APPROACH & RESULTS Before modeling OTCD, we addressed the question of why hiPSC-Heps generally secrete less urea than adult primary human hepatocytes (PHHs). Since hiPSC-Heps are not completely differentiated and maintain some characteristics of fetal PHHs, we compared gene expression levels in human fetal and adult liver tissue to identify genes responsible for reduced urea secretion in hiPSC-Heps. We found lack of aquaporin 9 (AQP9) expression in fetal liver tissue as well as in hiPSC-Heps, and showed that forced expression of AQP9 in hiPSC-Heps restores urea secretion and normalizes the response to ammonia challenge by increasing ureagenesis. Furthermore, we proved functional ureagenesis by challenging AQP9-expressing hiPSC-Heps with ammonium chloride labeled with the stable isotope [15 N] (15 NH4 Cl) and by assessing enrichment of [15 N]-labeled urea. Finally, using hiPSC-Heps derived from patients with OTCD, we generated a liver disease model that recapitulates the hepatic manifestation of the human disease. Restoring OTC expression-together with AQP9-was effective in fully correcting OTC activity and normalizing ureagenesis as assessed by 15 NH4 Cl stable-isotope challenge. CONCLUSION Our results identify a critical role for AQP9 in functional urea metabolism and establish the feasibility of in vitro modeling of OTCD with hiPSC-Heps. By facilitating studies of OTCD genotype/phenotype correlation and drug screens, our model has potential for improving the therapy of OTCD.

Hepatic ammonia detoxification to urea is critical for the prevention of hyperammonemia and neurological damage. Hepatocyte mitochondrial aquaporin-8 (AQP8) channels have been involved in ammonia-derived ureagenesis. Herein, we studied whether the adenoviral gene transfer of human AQP8 (hAQP8) to hepatocyte mitochondria enhances ammonia conversion to urea. Using primary cultured rat hepatocytes, we first confirmed the mitochondrial expression of hAQP8 and then, using unlabeled or 15 N-labeled ammonia, we demonstrated that the urea synthesis was significantly enhanced in hAQP8-transduced hepatocytes. Studies using isolated hAQP8-expressing mitochondria also showed an increased ammonia metabolism. hAQP8 transduction was able to recover the impaired ammonia-derived ureagenesis in hepatotoxin-treated hepatocytes. Our data suggest that mitochondrially-expressed hAQP8 enhances and improves hepatocyte ammonia conversion to urea, a finding with potential therapeutic implications for liver disease with impaired ammonia detoxification.

Polyhydramnios is a common feature diagnosed by ultrasound in the second half of pregnancy. Biochemical analysis of amniotic fluid can be useful when suspecting Bartter syndrome or digestive atresia but in most of cases, no etiology of polyhydramnios is found because of the complex regulation of amniotic fluid. Aquaporins (AQP) are transmembrane channel proteins contributing to water transfers. Some of them are expressed in fetal membranes and placenta. Their expression has been shown to be disrupted in some pathological conditions such as maternal diabetes, often associated with polyhydramnios. AQP-1, 3 and 8 levels in amniotic fluid were retrospectively measured in patients suffering from polyhydramnios (n=21) from 23 weeks of gestation (WG). They were compared to the levels observed in control subjects (n=96) and their relationship with maternal factors and neonatal issues was analyzed. AQP-1, 3, 8 levels were physiologically fluctuating, AQP-1 levels always being the lowest and AQP-3 the highest, with a significant decrease at the end of pregnancy. AQPs/AFP ratios increased about 8 folds during pregnancy, their kinetic profiles reflecting physiological dynamic evolution of amniotic fluid volume. In polyhydramnios, AQP-3 level tended to be decreased whereas AQP-8 level was decreased from mid-gestation whatever the etiology of polyhydramnios. No significant relationship was found between AQPs levels and either the fetal prematurity degree or macrosomia. No specific pattern was observed in idiopathic polyhydramnios, limiting the interest of AQPs dosage in amniotic fluid in the management of those complicated pregnancies.

Research into the glymphatic system reached an inflection point with steep trajectory in 2012 when it was formally recognized and named, but the historical roots for it are solid and deep, dating back to pioneers such as Cushing, Weed, and Dandy. We provide an overview of key discoveries of the glymphatic system, which promotes bulk flow of fluid and solutes throughout the brain parenchyma. We also discuss the lymphatic drainage of the central nervous system. Evidence is building that failure of the glymphatic system causes glymphedema in patients commonly managed by neurocritical care and neurosurgery specialists. We review research supporting this for decompressive craniectomy, subarachnoid hemorrhage, and normal-pressure hydrocephalus. We argue that it is time for a paradigm shift from the traditional model of cerebrospinal fluid circulation to a revised model that incorporates the glymphatic pathway and lymphatic clearance. These recent breakthroughs will inspire new therapeutic approaches to recognize, reverse, and restore glymphatic dysfunction and to leverage this pathway to deliver brain-wide therapeutics.

© 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved., Preeclampsia (PE), a pregnancy disorder influenced by oxidative stress and hypoxia, affects the health of the mother and baby and is associated with an increased risk of future hypertension (HT). Aquaporins are a family of water channels, comprising members that also transport glycerol (aquaglyceroporins) and hydrogen peroxide (peroxiporins), key molecules for metabolic homeostasis and redox signaling. Here, we investigated the association of Aquaporin-3 (AQP3; rs2231231), Aquaporin-7 (AQP7; rs2989924), NOS3 (4B/A intron) and CYBA (rs4673) genetic polymorphisms with the development of hypertensive disorders by qPCR/PCR in a cohort of 150 normotensive (NT) women (N = 90) or with previous PE (N = 60) during pregnancy. Prospectively, women were reclassified 2-16 years after pregnancy as NT (N = 98) or hypertensive (N = 48) and the genetic associations were reevaluated. In addition, genetic associations were reevaluated and compared between normotensive and hypertensive (HT) subjects. We found that AQP3 rs2231231, an aquaglyceroporin/peroxiporin, is associated with the development of HT, whereas AQP7, NOS3 and CYBA polymorphism did not correlate with PE or future HT. Because AQP3 was associated with hypertension only after pregnancy, its role might be related to later risk factors of hypertension such as metabolic syndrome or oxidative stress., This research was funded by Fundação para a Ciência e Tecnologia (FCT), Portugal, through individual fellowship to IV da Silva (PD/BD/113634/2015), grant PTDC/BTM-SAL/28977/2017 and strategic projects UIDB/04138/2020 and UIDP/04138/2020 (iMed.ULisboa) and UIDB/04378/2020.

Intestinal epithelial cells (IECs) are an important point of contact between dietary food components consumed and subsequent whole-body utilization for body maintenance and growth. Selective bioactive phenolic acids, widely present in fruits, vegetables and beverages can generate hydrogen peroxide (H

Schizophrenia (SCZ) is a debilitating mental disorder with various causes involving complex interactions between genetic factors and environmental agents. The immune system plays a vital role in the pathology and function of the nervous system. Interleukin 35 (IL-35) is a regulatory and anti-inflammatory cytokine that can prevent autoimmune and inflammatory diseases. This study aimed to investigate the role of autoantibodies against some central nervous system (CNS) antigens and IL-35 serum levels in patients with Schizophrenia. This case-control study involved 80 participants. The serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the autoantibodies in the CNS by indirect immunofluorescence assay (IFA). The serum levels of IL-35 were decreased in patient groups compared to healthy subjects. Autoantibodies against N-methyl-D-aspartate receptor (NMDAR) and myelin-associated glycoprotein (MAG) were positive in 15% (6/40) and 7.5% (3/40), respectively; however, no antibodies against myelin, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), voltage-gated potassium channel (VGKC), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), γ-butyric acid receptor type B1 γ-butyric acid receptor type B1 (GABABR), antidipeptidyl peptidase-like protein-6 (DPPX), immunoglobulin-like cell adhesion molecule 5 (IgLON5), Glycine receptor (R) and acetylcholine receptor (Ach R) were detected (No statistics were computed). We found that decreased serum IL-35 levels and the existence autoantibodies against NMDAR antigen may contribute to the pathogenesis of SCZ.

Some aquaporins (AQPs) allow the diffusion of hydrogen peroxide (H2O2), the most abundant ROS, through the cell membranes. Therefore, the possibility of regulating the AQP-mediated permeability to H2O2, and thus ROS scavenging, appears particularly important for controlling the redox state of cells in physiological and pathophysiological conditions. Several compounds have been screened and characterized for this purpose. This study aimed to analyze the effect of cerium oxide nanoparticles (CNPs) presenting antioxidant activity on AQP functioning. HeLa cells express AQP3, 6, 8, and 11, able to facilitate H2O2. AQP3, 6, and 8 are expressed in the plasma membrane and intracellularly, while AQP11 resides only in intracellular structures. CNPs but not cerium ions treatment significantly increased the water and H2O2 permeability by interacting with AQP3, 6, and especially with AQP8. CNPs increased considerably the AQP-mediated water diffusion in cells with oxidative stress. Functional experiments with silenced HeLa cells revealed that CNPs increased the H2O2 diffusion mainly by modulating the AQP8 permeability but also the AQP3 and AQP6, even if to a lesser extent. Current findings suggest that CNPs represent a promising pharmaceutical agent that might potentially be used in numerous pathologies involving oxidative stress as tumors and neurodegenerative diseases.

Dental handpieces (DHPs) are reusable invasive medical devices that must be cleaned, decontaminated, lubricated and steam sterilized after use. DHPs have a complex internal design including narrow channels, contamination of which can compromise sterilization. DHPs are not designed for routine disassembly, making cleaning/decontamination efficacy difficult to monitor. Washer-disinfection is the preferred method of decontaminating DHPs, but few studies have investigated its direct effectiveness at reducing microbial contamination internally.To use contra-angle DHPs as a model system to investigate the effectiveness of washer-disinfection at reducing microbial contamination of internal components of multiple DHPs.The air and water channels and heads of 10 disassembled contra-angle DHPs (BienAir, Biel/Bienne, Switzerland) were inoculated separately with 10On average, an approximate 5 log or greater reduction in microbial cfu and a93% reduction in protein from DHP heads and channels was consistently recorded following washer-disinfection for all DHPs under all conditions tested.The internal components of multiple DHPs can be effectively cleaned and decontaminated by washer-disinfection.

Aquaporin water channels (AQPs) are membrane proteins that maintain cellular water homeostasis. The interactions between human AQPs and other proteins play crucial roles in AQP regulation by both gating and trafficking. Here, we describe a protocol for characterizing the interaction between a human AQP and a soluble interaction partner using microscale thermophoresis (MST). MST has the advantage of low sample consumption and high detergent compatibility enabling AQP protein-protein interaction investigation with a high level of control of components and environment. For complete details on the use and execution of this protocol, please refer to Kitchen et al. (2020) and Roche et al. (2017).

Aquaporins (AQPs) are transmembrane channels essential for water, energy, and redox homeostasis, with proven involvement in a variety of pathophysiological conditions such as edema, glaucoma, nephrogenic diabetes insipidus, oxidative stress, sepsis, cancer, and metabolic dysfunctions. The 13 AQPs present in humans are widely distributed in all body districts, drawing cell lineage-specific expression patterns closely related to cell native functions. Compelling evidence indicates that AQPs are proteins with great potential as biomarkers and targets for therapeutic intervention. Aquaporin-9 (AQP9) is the most expressed in the liver, with implications in general metabolic and redox balance due to its aquaglyceroporin and peroxiporin activities, facilitating glycerol and hydrogen peroxide (H2O2) diffusion across membranes. AQP9 is also expressed in other tissues, and their altered expression is described in several human diseases, such as liver injury, inflammation, cancer, infertility, and immune disorders. The present review compiles the current knowledge of AQP9 implication in diseases and highlights its potential as a new biomarker for diagnosis and prognosis in clinical medicine.

The glycerol channel AQP7 facilitates glycerol efflux from adipose tissue (AT), and AQP7 deficiency has been suggested to promote obesity. However, the release of glycerol from AT is not fully blocked in AQP7-deficient mice, which suggests that either alternative glycerol channels are present in AT or significant simple diffusion of glycerol occurs. Previous investigations of the expression of other aquaglyceroporins (AQP3, AQP9, AQP10) than AQP7 in AT are contradictory. Therefore, we here aim at determining the cellular localization of AQP3 and AQP9 in addition to AQP7 in human and mouse AT using well-characterized antibodies for immunohistochemistry (IHC) and immunoblotting as well as available single-cell transcriptomic data from human and mouse AT. We confirm that AQP7 is expressed in endothelial cells and adipocytes in human AT and find ex vivo evidence for interaction between AQP7 and perilipin-1 in adipocytes. In addition, labeling for AQP7 in human AT also includes CD68-positive cells. No labeling for AQP3 or AQP9 was identified in endothelial cells or adipocytes in human or mouse AT using IHC. Instead, in human AT, AQP3 was predominantly found in erythrocytes, whereas AQP9 expression was observed in a small number of CD15-positive cells. The transcriptomic data revealed that AQP3 mRNA was found in a low number of cells in most of the identified cell clusters, whereas AQP9 mRNA was found in myeloid cell clusters as well as in clusters likely representing mesothelial progenitor cells. No AQP10 mRNA was identified in human AT. In conclusion, the presented results do not suggest a functional overlap between AQP3/AQP9/AQP10 and AQP7 in human or mouse white AT.

BACKGROUND Colon cancer survival is dependent on metastatic potential and treatment. Large RNA-sequencing data sets may assist in identifying colon cancer-specific biomarkers to improve patient outcomes. OBJECTIVE This study aimed to identify a highly specific biomarker for overall survival in colon adenocarcinoma by using an RNA-sequencing data set. DESIGN Raw RNA-sequencing and clinical data for patients with colon adenocarcinoma (n = 271) were downloaded from The Cancer Genome Atlas. A binomial regression model was used to calculate differential RNA expression between paired colon cancer and normal epithelium samples (n = 40). Highly differentially expressed RNAs were examined. SETTINGS This study was conducted at the University of Louisville using data acquired by The Cancer Genome Atlas. PATIENTS Patients from US accredited cancer centers between 1998 and 2013 were analyzed. MAIN OUTCOME MEASURES The primary outcome measures were recurrence-free and overall survival. RESULTS The median age was 66 years (147/271 men, 180/271 White patients). Thirty RNAs were differentially expressed in colon adenocarcinoma compared with paired normal epithelium, using a log-fold change cutoff of ±6. Using median expression as a cutoff, 4 RNAs were associated with worse overall survival: decreased ZG16 (log-rank = 0.023), aquaporin 8 (log-rank = 0.023), and SLC26A3 (log-rank = 0.098), and increased COL1A1 (log-rank = 0.105). On multivariable analysis, low aquaporin 8 expression (HR, 1.748; 95% CI, 1.016-3.008; p = 0.044) was a risk factor for worse overall survival. Our final aquaporin 8 model had an area under the curve of 0.85 for overall survival. On subgroup analysis, low aquaporin 8 was associated with worse overall survival in patients with high microsatellite instability and in patients with stage II disease. Low aquaporin 8 expression was associated with KRAS and BRAF mutations. Aquaporin 8 immunohistochemistry was optimized for clinical application. LIMITATIONS This was a retrospective study. CONCLUSION Aquaporin 8 is a water channel selectively expressed in normal colon tissue. Low aquaporin 8 expression is a risk factor for worse overall survival in patients who have colon cancer. Aquaporin 8 measurement may have a role as a colon-specific prognostic biomarker and help in patient risk stratification for increased surveillance. See Video Abstract at http://links.lww.com/DCR/B603. LA DISMINUCIN DE LA EXPRESIN TUMORAL DE LA ACUAPORINA DEL CANAL DE AGUA ESPECFICO DEL COLON SE ASOCIA CON UNA REDUCCIN DE LA SUPERVIVENCIA GENERAL EN EL ADENOCARCINOMA DE COLON ANTECEDENTES:La supervivencia del cancer de colon depende del potencial metastasico y del tratamiento. Grandes conjuntos de datos de secuenciacion de ARN pueden ayudar a identificar biomarcadores especificos del cancer de colon para mejorar los resultados de los pacientes.OBJETIVO:Identificar un biomarcador altamente especifico para la supervivencia general en el adenocarcinoma de colon utilizando un conjunto de datos de secuenciacion de ARN.DISENO:La secuenciacion de ARN sin procesar y los datos clinicos para pacientes con adenocarcinoma de colon (n = 271) se descargaron de The Cancer Genome Atlas. Se utilizo un modelo de regresion binomial para calcular la expresion diferencial de ARN entre muestras de cancer de colon emparejadas y muestras de epitelio normal (n = 40). Se examinaron los ARN expresados de forma altamente diferencial.ENTORNO CLINICO:Este estudio se realizo en la Universidad de Louisville utilizando datos adquiridos por The Cancer Genome Atlas.PACIENTES:Se analizaron pacientes de centros oncologicos acreditados en Estados Unidos entre 1998-2013.PRINCIPALES MEDIDAS DE VALORACION:Las principales medidas de valoracion fueron la supervivencia general y libre de recurrencia.RESULTADOS:La mediana de edad fue de 66 anos (147/271 hombres, 180/271 caucasicos). Treinta ARN se expresaron diferencialmente en el adenocarcinoma de colon en comparacion con el epitelio normal emparejado, utilizando un limite de cambio logaritmico de ± 6. Utilizando la expresion mediana como punto de corte, cuatro ARN se asociaron con una peor supervivencia general: disminucion de ZG16 (rango logaritmico = 0,023), acuaporina8 (rango logaritmico = 0,023) y SLC26A3 (rango logaritmico = 0,098) y aumento de COL1A1 (log -rango = 0,105). En el analisis multivariable, la baja expresion de acuaporina8 (HR = 1,748, IC del 95%: 1,016-3,008, p = 0,044) fue un factor de riesgo para una peor supervivencia global. Nuestro modelo de aquaporin8 final tuvo un AUC de 0,85 para la supervivencia global. En el analisis de subgrupos, la acuaporina8 baja se asocio con una peor supervivencia general en pacientes con MSI-H y en pacientes en estadio II. La baja expresion de acuaporina8 se asocio con mutaciones de KRAS y BRAF. La inmunohistoquimica de aquaporina8 se optimizo para su aplicacion clinica.LIMITACIONES:Este fue un estudio retrospectivo.CONCLUSION:La acuaporina8 es un canal de agua expresado selectivamente en el tejido normal del colon. La baja expresion de AQP8 es un factor de riesgo de peor supervivencia global en pacientes con cancer de colon. La medicion de aquaporina8 puede tener un papel como un biomarcador de pronostico especifico del colon y ayudar en la estratificacion del riesgo del paciente para una mayor vigilancia. Consulte Video Resumen en http://links.lww.com/DCR/B603.

Structurally, aquaporins (AQPs) are small channel proteins with monomers of ~ 30 kDa that are assembled as tetramers to form pores on cell membranes. Aquaporins mediate the conduction of water but at times also small solutes including glycerol across cell membranes and along osmotic gradients. Thirteen isoforms of AQPs have been reported in mammalian cells, and several of these are likely expressed in platelets. Osmotic swelling mediated by AQP1 sustains the calcium entry required for platelet phosphatidylserine exposure and microvesiculation, through calcium permeable stretch-activated or mechanosensitive cation channels. Notably, deletion of AQP1 diminishes platelet procoagulant membrane dynamics in vitro and arterial thrombosis in vivo, independent of platelet granule secretion and without affecting hemostasis. Water entry into platelets promotes procoagulant activity, and AQPs may also be critical for the initiation and progression of venous thrombosis. Platelet AQPs may therefore represent valuable targets for future development of a new class of antithrombotics, namely, anti-procoagulant antithrombotics, that are mechanistically distinct from current antithrombotics. However, the structure of AQPs does not make for easy targeting of these channels, hence they remain elusive drug targets. Nevertheless, thrombosis data in animal models provide compelling reasons to continue the pursuit of AQP-targeted antithrombotics. In this review, we discuss the role of aquaporins in platelet secretion, aggregation and procoagulation, the challenge of drugging AQPs, and the prospects of targeting AQPs for arterial and venous antithrombosis.

Background: The aquaporins (AQPs) are transcellular proteins that majorly consist of a tetrametric hour-glass like structure. AQPs have a definitive function in transpositioning of water and solutes across cell membrane. This review provides information regarding structure, expression and functions of AQPs in the human body. The purpose of this review is to provide a comprehensive summary of physiological and pathophysiological correlations related to AQPs and their therapeutic implications. Absence or mutations of different aquaporins are believed to be linked to clinical diseases including Sjogren’s Syndrome, nephrogenic diabetes insipidus, liver dysfunction and obesity. Modern therapeutic techniques are utilizing aquaporins in gene therapy for Sjogren’s Syndrome and cholestasis. In conclusion, this study provides a comprehensive description of localization, function, abnormal clinical conditions and therapeutic implications of aquaporin proteins. Keywords: Classification, Clinical, Human Aquaporins, Localization, Continuous....

A massive localized trauma to the spinal cord results in complex pathologic events driven by necrosis and vascular damage which in turn leads to hemorrhage and edema. Severe, destructive and very protracted inflammatory response is characterized by infiltration by phagocytic macrophages of a site of injury which is converted into a cavity of injury (COI) surrounded by astroglial reaction mounted by the spinal cord. The tissue response to the spinal cord injury (SCI) has been poorly understood but the final outcome appears to be a mature syrinx filled with the cerebrospinal fluid with related neural tissue loss and permanent neurologic deficits. This paper reviews known pathologic mechanisms involved in the formation of the COI after SCI and discusses the integrative role of reactive astrogliosis in mechanisms involved in the removal of edema after the injury. A large proportion of edema fluid originating from the trauma and then from vasogenic edema related to persistent severe inflammation, may be moved into the COI in an active process involving astrogliosis and specifically over-expressed aquaporins.

Background: Schistosomiasis (snail fever/bilharzia), a disease caused by parasitic flatworms (schistosomes), infects millions of people worldwide. Aquaporins from these organisms were found to be a potent drug target. Introduction: We investigate the possible mechanism of inhibition of Aquaporin (AQP) from S.mansoni by 5 drug molecules (Praziquantel, Metrifonate, Artimisinin, Albendazole, and Amoscanate). Methods: 3D molecular structure of Aquaporin was obtained through homology modeling and further protein-ligand docking and MD simulation were performed. Results: VAL-75, ASN-91, ALA-220, ASN-222, ARG-225 amino acids were found to play crucial role in ligand binding. TRP-71 and other important residues play major role in hydrophobic interactions stabilizing protein-ligand complexes. Conclusion: We hope that this study (with the newly identified aquaporin target) will support the development of structure and pharmacophore-based novel S. mansoni drugs to control and curb Schistosomiasis.