The Experts below are selected from a list of 92397 Experts worldwide ranked by ideXlab platform
Nicholas G Verne - One of the best experts on this subject based on the ideXlab platform.
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intestinal Membrane Permeability and hypersensitivity in the irritable bowel syndrome
Pain, 2009Co-Authors: Qiqi Zhou, Buyi Zhang, Nicholas G VerneAbstract:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal Permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate that diarrhea-predominant IBS (D-IBS) patients display increased intestinal Permeability. We have also found that increased intestinal Membrane Permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal Membrane Permeability using the lactulose/mannitol method. All subjects ingested 5g of lactulose and 2g of mannitol in 100ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue scale (M-VAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients had increased intestinal Membrane Permeability as measured by the lactulose/mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal Permeability had a higher FBDSI score (100.8 + or - 5.4) than IBS patients with normal Membrane Permeability and sensitivity (51.6 + or - 12.7) and controls (6.1 + or - 5.6) (p<0.001). A subset of D-IBS patients had increased intestinal Membrane Permeability that was associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal Membrane Permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.
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microrna 29a regulates intestinal Membrane Permeability in patients with irritable bowel syndrome
Gut, 2009Co-Authors: Qiqi Zhou, Wiley W Souba, Carlo M Croce, Nicholas G VerneAbstract:Background The molecular mechanisms underlying the pathophysiology of irritable bowel syndrome (IBS) are poorly understood. One mechanism may involve increased intestinal Permeability that is reversed with glutamine supplementation. Our goal was to evaluate the expression of glutamine synthetase and its complementary miRNA in blood microvesicles and gut tissues of IBS patients with increased intestinal Membrane Permeability. Methods We evaluated 19 diarrhoea-predominant IBS patients and 10 controls for intestinal Membrane Permeability using the lactulose/mannitol method. miRNA expression was evaluated in blood microvesicles and gut tissue. To further confirm the relationship between miRNA and glutamine synthetase expression, cell culture experiments were conducted. Glutamine synthetase was also evaluated in the gut tissues of patients. Results A subset of patients with IBS (8/19, 42%) had increased intestinal Membrane Permeability and decreased glutamine synthetase expression compared to patients with IBS normal Membrane Permeability, and to controls. Expression of miR-29a was increased in blood microvesicles, small bowel and colon tissues of IBS patients with increased intestinal Membrane Permeability. Increased intestinal Permeability was modulated by miR-29a which has a complementary site in the 3′-UTR of the GLUL gene. Conclusions The results support the conclusion that GLUL regulates intestinal Membrane Permeability and miR-29a regulates both GLUL and intestinal Membrane Permeability. The data suggests that miR-29a effects on intestinal Membrane Permeability may be due to its regulation of GLUL. Targeting this signalling pathway could lead to a new therapeutic approach to the treatment of patients with IBS, especially because small molecules that mimic or inhibit miRNA-based mechanisms are readily available.
Tristan Bereau - One of the best experts on this subject based on the ideXlab platform.
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data driven equation for drug Membrane Permeability across drugs and Membranes
Journal of Chemical Physics, 2021Co-Authors: Arghya Dutta, Jilles Vreeken, Luca M Ghiringhelli, Tristan BereauAbstract:Drug efficacy depends on its capacity to permeate across the cell Membrane. We consider the prediction of passive drug–Membrane Permeability coefficients. Beyond the widely recognized correlation with hydrophobicity, we additionally consider the functional relationship between passive permeation and acidity. To discover easily interpretable equations that explain the data well, we use the recently proposed sure-independence screening and sparsifying operator (SISSO), an artificial-intelligence technique that combines symbolic regression with compressed sensing. Our study is based on a large in silico dataset of 0.4 × 106 small molecules extracted from coarse-grained simulations. We rationalize the equation suggested by SISSO via an analysis of the inhomogeneous solubility–diffusion model in several asymptotic acidity regimes. We further extend our analysis to the dependence on lipid-Membrane composition. Lipid-tail unsaturation plays a key role but surprisingly contributes stepwise rather than proportionally. Our results are in line with previously observed changes in Permeability, suggesting the distinction between liquid-disordered and liquid-ordered permeation. Together, compressed sensing with analytically derived asymptotes establish and validate an accurate, broadly applicable, and interpretable equation for passive Permeability across both drug and lipid-tail chemistry.
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data driven equation for drug Membrane Permeability across drugs and Membranes
arXiv: Chemical Physics, 2020Co-Authors: Arghya Dutta, Jilles Vreeken, Luca M Ghiringhelli, Tristan BereauAbstract:Drug efficacy depends on its capacity to permeate across the cell Membrane. We consider the prediction of passive drug-Membrane Permeability coefficients. Beyond the widely recognized correlation with hydrophobicity, we apply sure-independence screening and sparsifying operator (SISSO), a data-driven compressed-sensing technique, to a large (0.4 million compounds) database of coarse-grained computer simulations as a way to also incorporate the role of acidity. We rationalize our derived equation by means of an analysis of the inhomogeneous solubility-diffusion model in several asymptotic acidity regimes. We further extend our analysis to the dependence on lipid-Membrane composition. Lipid-tail unsaturation plays a key role: we report a Permeability ratio between liquid-disordered (Ld) and liquid-ordered (Lo) domains of roughly 25, largely independent of the chemistry of the drug. They confirm the role of Membrane surface-density fluctuations in passive permeation. Together, compressed sensing with analytically derived asymptotes establish and validate an accurate, broadly applicable, and interpretable equation for passive Permeability across both drug and lipid-tail chemistry.
Shigeomi Shimizu - One of the best experts on this subject based on the ideXlab platform.
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role of the mitochondrial Membrane Permeability transition in cell death
Apoptosis, 2007Co-Authors: Yoshihide Tsujimoto, Shigeomi ShimizuAbstract:In recent years, the role of the mitochondria in both apoptotic and necrotic cell death has received considerable attention. An increase of mitochondrial Membrane Permeability is one of the key events in apoptotic or necrotic death, although the details of the mechanism involved remain to be elucidated. The mitochondrial Membrane Permeability transition (MPT) is a Ca2+-dependent increase of mitochondrial Membrane Permeability that leads to loss of Δψ, mitochondrial swelling, and rupture of the outer mitochondrial Membrane. The MPT is thought to occur after the opening of a channel that is known as the Permeability transition pore (PTP), which putatively consists of the voltage-dependent anion channel (VDAC), the adenine nucleotide translocator (ANT), cyclophilin D (Cyp D: a mitochondrial peptidyl prolyl-cis, trans-isomerase), and other molecule(s). Recently, significant progress has been made by studies performed with mice lacking Cyp D at several laboratories, which have convincingly demonstrated that Cyp D is essential for the MPT to occur and that the Cyp D-dependent MPT regulates some forms of necrotic, but not apoptotic, cell death. Cyp D-deficient mice have also been used to show that the Cyp D-dependent MPT plays a crucial role in ischemia/reperfusion injury. The anti-apoptotic proteins Bcl-2 and Bcl-xL have the ability to block the MPT, and can therefore block MPT-dependent necrosis in addition to their well-established ability to inhibit apoptosis.
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role of the mitochondrial Membrane Permeability transition in cell death
Apoptosis, 2007Co-Authors: Yoshihide Tsujimoto, Shigeomi ShimizuAbstract:In recent years, the role of the mitochondria in both apoptotic and necrotic cell death has received considerable attention. An increase of mitochondrial Membrane Permeability is one of the key events in apoptotic or necrotic death, although the details of the mechanism involved remain to be elucidated. The mitochondrial Membrane Permeability transition (MPT) is a Ca(2+)-dependent increase of mitochondrial Membrane Permeability that leads to loss of Deltapsi, mitochondrial swelling, and rupture of the outer mitochondrial Membrane. The MPT is thought to occur after the opening of a channel that is known as the Permeability transition pore (PTP), which putatively consists of the voltage-dependent anion channel (VDAC), the adenine nucleotide translocator (ANT), cyclophilin D (Cyp D: a mitochondrial peptidyl prolyl-cis, trans-isomerase), and other molecule(s). Recently, significant progress has been made by studies performed with mice lacking Cyp D at several laboratories, which have convincingly demonstrated that Cyp D is essential for the MPT to occur and that the Cyp D-dependent MPT regulates some forms of necrotic, but not apoptotic, cell death. Cyp D-deficient mice have also been used to show that the Cyp D-dependent MPT plays a crucial role in ischemia/reperfusion injury. The anti-apoptotic proteins Bcl-2 and Bcl-x(L) have the ability to block the MPT, and can therefore block MPT-dependent necrosis in addition to their well-established ability to inhibit apoptosis.
Qiqi Zhou - One of the best experts on this subject based on the ideXlab platform.
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intestinal Membrane Permeability and hypersensitivity in the irritable bowel syndrome
Pain, 2009Co-Authors: Qiqi Zhou, Buyi Zhang, Nicholas G VerneAbstract:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal Permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate that diarrhea-predominant IBS (D-IBS) patients display increased intestinal Permeability. We have also found that increased intestinal Membrane Permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal Membrane Permeability using the lactulose/mannitol method. All subjects ingested 5g of lactulose and 2g of mannitol in 100ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue scale (M-VAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients had increased intestinal Membrane Permeability as measured by the lactulose/mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal Permeability had a higher FBDSI score (100.8 + or - 5.4) than IBS patients with normal Membrane Permeability and sensitivity (51.6 + or - 12.7) and controls (6.1 + or - 5.6) (p<0.001). A subset of D-IBS patients had increased intestinal Membrane Permeability that was associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal Membrane Permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.
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microrna 29a regulates intestinal Membrane Permeability in patients with irritable bowel syndrome
Gut, 2009Co-Authors: Qiqi Zhou, Wiley W Souba, Carlo M Croce, Nicholas G VerneAbstract:Background The molecular mechanisms underlying the pathophysiology of irritable bowel syndrome (IBS) are poorly understood. One mechanism may involve increased intestinal Permeability that is reversed with glutamine supplementation. Our goal was to evaluate the expression of glutamine synthetase and its complementary miRNA in blood microvesicles and gut tissues of IBS patients with increased intestinal Membrane Permeability. Methods We evaluated 19 diarrhoea-predominant IBS patients and 10 controls for intestinal Membrane Permeability using the lactulose/mannitol method. miRNA expression was evaluated in blood microvesicles and gut tissue. To further confirm the relationship between miRNA and glutamine synthetase expression, cell culture experiments were conducted. Glutamine synthetase was also evaluated in the gut tissues of patients. Results A subset of patients with IBS (8/19, 42%) had increased intestinal Membrane Permeability and decreased glutamine synthetase expression compared to patients with IBS normal Membrane Permeability, and to controls. Expression of miR-29a was increased in blood microvesicles, small bowel and colon tissues of IBS patients with increased intestinal Membrane Permeability. Increased intestinal Permeability was modulated by miR-29a which has a complementary site in the 3′-UTR of the GLUL gene. Conclusions The results support the conclusion that GLUL regulates intestinal Membrane Permeability and miR-29a regulates both GLUL and intestinal Membrane Permeability. The data suggests that miR-29a effects on intestinal Membrane Permeability may be due to its regulation of GLUL. Targeting this signalling pathway could lead to a new therapeutic approach to the treatment of patients with IBS, especially because small molecules that mimic or inhibit miRNA-based mechanisms are readily available.
Guillermo Reglero - One of the best experts on this subject based on the ideXlab platform.
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in vitro Permeability of saponins and sapogenins from seed extracts by the parallel artificial Membrane Permeability assay effect of in vitro gastrointestinal digestion
Journal of Agricultural and Food Chemistry, 2020Co-Authors: Joaquin Navarro Del Hierro, Vieri Piazzini, Guillermo Reglero, Diana Martin, Maria Camilla BergonziAbstract:The Permeability of saponins and sapogenins from fenugreek and quinoa extracts, as well as dioscin and diosgenin, was evaluated by the parallel artificial Membrane Permeability assay (PAMPA). The e...