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Computational and Mathematical Methods... 2022Functional dyspepsia (FD) is a common digestive system disease, and probiotics in the treatment of FD have a good curative effect. Patients with gastrointestinal...
Functional dyspepsia (FD) is a common digestive system disease, and probiotics in the treatment of FD have a good curative effect. Patients with gastrointestinal diseases often show a poor response to traditional drug treatments and suffer from adverse reactions. Kvass can be used as a functional drink without side effects to improve the symptoms of FD patients. The results showed that compared with those of the model group, the body weight and food intake of the treatment group were significantly increased ( < 0.05), and the gastric residual rate of the treatment group was significantly decreased ( < 0.05); the amount of pepsin in the treatment group was significantly higher than that in the model group ( < 0.05); a high dose of Kvass could increase the contents of ghrelin, motilin (MTL), and gastrin (GAS) in the plasma and decrease the contents of vasoactive intestinal peptide (VIP) in the plasma; the contents of ghrelin, MTL, and GAS in the gastric antrum were also increased in the high-dose group. Kvass beverage can significantly improve the gastrointestinal function of rats, which may be because it can improve the contents of ghrelin, MTL, GAS, and VIP in both the serum and gastric antrum by regulating the expression of short-chain fatty acids in the colon.
Topics: Animals; Dyspepsia; Gastrointestinal Motility; Ghrelin; Motilin; Rats; Stomach; Vasoactive Intestinal Peptide
PubMed: 35799630
DOI: 10.1155/2022/5169892 -
BMC Ophthalmology Aug 2019Exploring the role of vasoactive intestinal peptide (VIP) in the lateral geniculate body (LGBd) in visual development and studying the therapeutic effect of VIP on...
BACKGROUND
Exploring the role of vasoactive intestinal peptide (VIP) in the lateral geniculate body (LGBd) in visual development and studying the therapeutic effect of VIP on amblyopic kittens.
METHODS
Three-week-old domestic cats were divided into a control group (n = 10) and a monocular deprivation group (n = 20), with an eye mask covering the right eye of those in the deprived group. After pattern visual evoked potential (PVEP) recording confirmed the formation of monocular amblyopia, the left LGBd was isolated from 5 kittens in each group. The remaining control kittens continued to be raised, and the remaining deprivation group was divided into a VIP intervention group (n = 5), Sefsol (caprylic acid monoglyceride, VIP solution) intervention group (n = 5) and amblyopia non-intervention group (n = 5) after removal of the eye mask. Three weeks later, PVEPs, VIP immunohistochemistry and VIP mRNA expression in the left LGBd were compared across groups.
RESULTS
At 6 weeks of age, there were significant differences in P100 wave latency and amplitude and VIP immunohistochemistry and in situ hybridization between the control group and the deprivation group (P < 0.05). After 3 weeks of the corresponding interventions, the latency and amplitude in the VIP intervention group were better than that in the Sefsol intervention group and amblyopia non-intervention group (P < 0.05). Furthermore, VIP treatment increased the number of immunohistochemical VIP-positive cells (P < 0.05) and the average optical density of positive cells (P > 0.05), as well as the number (P < 0.05) and average optical density of VIP mRNA-positive cells (P < 0.05).
CONCLUSIONS
VIP plays an important role in visual development. Nasal administration of VIP can improve the function of neurons in the LGBd of kittens and has a certain therapeutic effect on amblyopia.
Topics: Amblyopia; Animals; Cats; Disease Models, Animal; Evoked Potentials, Visual; Female; Immunohistochemistry; Sensory Deprivation; Vasoactive Intestinal Peptide; Visual Cortex
PubMed: 31429729
DOI: 10.1186/s12886-019-1203-1 -
Inflammatory Bowel Diseases Feb 2019The appendix contains copious lymphoid tissue and is constantly exposed to gut flora. Appendicitis followed by appendectomy (AA), when done at a young age, prevents or... (Review)
Review
The appendix contains copious lymphoid tissue and is constantly exposed to gut flora. Appendicitis followed by appendectomy (AA), when done at a young age, prevents or significantly ameliorates inflammatory bowel diseases (IBDs) in later life. Inflammatory bowel disease comprises Crohn's disease and ulcerative colitis. Our unique murine AA model is the only existing experimental model of AA. Herein, the appendiceal pathology closely resembles the pathological features of human appendicitis. Our AA model protects against experimental colitis in an age-, bacteria- and antigen-dependent manner. Appendicitis-appendectomy performed in the most proximal colon curbs T helper 17 (Th17) cell activity, diminishes autophagy, modulates interferon activity-associated molecules, and suppresses endothelin vasoactivity-mediated immunopathology in the most distal colon. These changes induced by AA contribute to limiting colitis pathology. Manipulating and modulating various aspects of these pathways, pathophysiology, and molecular interactions will assist the development of novel therapeutic options to manage IBD. Competitive inhibition of the Th17 cell recruitment factor CCL20 or the chemokine CCL17 with antibodies, combinatorial peptides, or small molecules may limit colitic pathology. The chemokines CCL5 and CXCL11 could be investigated as potential therapies. Inhibition of the autophagy-associated molecules VPS15, LAMP2, LC3A, XBP1, or ULK1 may decrease colitic pathology. Curtailing endothelin-activity may decrease colitic impact. The antiproliferative, immunomodulatory molecules IFIT1, IFIT2, IFIT3, and IFI44 may have direct therapeutic value in ameliorating colitis. The molecules IRF4, IRF8, IRF2BP1, IFRD1, and IFRD2 are potentially good target molecules to competitively inhibit towards curbing colitis.
Topics: Animals; Appendectomy; Appendicitis; Chemokines; Colitis; Disease Models, Animal; Humans; Mice
PubMed: 30329049
DOI: 10.1093/ibd/izy332 -
Current Pharmaceutical Design 2018Parkinson's disease is the second most common neurodegenerative disorder in adults over the age of 65. The characteristic symptoms of Parkinson's disease, such as... (Review)
Review
Parkinson's disease is the second most common neurodegenerative disorder in adults over the age of 65. The characteristic symptoms of Parkinson's disease, such as resting tremor, muscular rigidity, bradykinesia, postural instability and gait imbalance, are thought to be a result of the progressive degeneration of the dopaminergic neurons of the substantia nigra compacta, resulting in insufficient dopamine integrated signalling on GABAergic medium spiny neurons in the striatum. Despite tremendous research, the molecular mechanisms underlying the pathogenesis of neurodegeneration in Parkinson's disease have remained largely unknown. Although a variety of possible pathogenic mechanisms have been proposed over the years, including excessive release of oxygen free radicals, impairment of mitochondrial function, loss of trophic support, abnormal kinase activity, disruption of calcium homeostasis, dysfunction of protein degradation and neuroinflammation, the pathogenesis is still largely uncertain, and there is currently no effective cure for Parkinson's disease. To develop potential therapies for Parkinson's disease, inflammatory processes, mitochondrial dynamics, oxidative stress, production of reactive aldehydes, excitotoxicity and synucleinopathies are to be targeted. In this respect, vasoactive intestinal peptide has beneficial effects that provide an advantage for the treatment of Parkinson's disease. Vasoactive intestinal peptide is a major neuropeptide-neurotransmitter having antioxidant, anti-inflammatory, neurotropic, neuromodulator, and anti-apoptotic properties. In addition to its direct neuroprotective actions regulating the activity of astrocytes, microglia and brain mast cells, it also plays important roles for neuronal adaptation, maintenance and survival.
Topics: Animals; Humans; Neuroprotective Agents; Parkinson Disease; Vasoactive Intestinal Peptide
PubMed: 30636594
DOI: 10.2174/1381612825666190111150953 -
Current Treatment Options in... Dec 2015Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency. Bleeding peptic ulcers account for the majority of causes in patients presenting with AUGIB,...
Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency. Bleeding peptic ulcers account for the majority of causes in patients presenting with AUGIB, whereas variceal bleeding in cirrhotic patients represents a more severe form of bleeding. Endoscopic therapy is the mainstay of treatment in patients with active bleeding, as it achieves hemostasis and improves patient outcomes. Pharmacotherapy is an important adjunct to endoscopic hemostasis. In the management of patients with bleeding peptic ulcers, acid suppression after endoscopic hemostasis reduces rates of further bleeding and interventions. In patients with stable hemodynamics awaiting endoscopy, acid suppression starts ulcer healing and downstages stigmata of bleeding, thereby reducing the need for endoscopic therapy. In managing patients with variceal bleeding, early administration of vasoactive drugs lowers splanchnic blood flow, promotes hemostasis, and makes subsequent endoscopic treatment easier. The use of vasoactive agents and antibiotics have both been shown to reduce mortality. In this review article, strategies of acid suppression therapy for peptic ulcer bleeds, vasoactive agents, and antibiotics for variceal bleeding, together with recent evidence on the use of tranexamic acid in gastrointestinal bleeding, are discussed.
PubMed: 26310578
DOI: 10.1007/s11938-015-0063-x -
Journal of Smooth Muscle Research =... 2021Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are major cell types that control vascular function, and hence dysfunction of these cells plays a key...
Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are major cell types that control vascular function, and hence dysfunction of these cells plays a key role in the development and progression of vasculopathies. Abnormal vascular responsiveness to vasoactive substances including vasoconstrictors and vasodilators has been observed in various arteries in diseases including diabetes, hypertension, chronic kidney diseases, and atherosclerosis. Several substances derived from ECs tightly control vascular function, such as endothelium-derived relaxing and contracting factors, and it is known that abnormal vascular signaling of these endothelium-derived substances is often observed in various diseases. Derangement of signaling in VSMCs and altered function influence vascular reactivity to vasoactive substances and tone, which are important determinants of vascular resistance and blood pressure. However, understanding the molecular mechanisms underlying abnormalities of vascular functions in pathological states is difficult because multiple substances interact in the development of these processes. Advanced glycation end products (AGEs), a heterogeneous group of bioactive compounds, are thought to contribute to vascular dysfunction, which in turn cause the development of several diseases including diabetes, hypertension, stroke, and atherosclerosis. A growing body of evidence suggests that AGEs could affect these cells and modulate vascular function. This study is focused on the link between AGEs and functions of ECs and VSMCs, particularly the modulative effects of AGEs on vascular reactivities to vasoactive substances.
Topics: Atherosclerosis; Endothelial Cells; Endothelium, Vascular; Glycation End Products, Advanced; Humans; Hypertension
PubMed: 35095032
DOI: 10.1540/jsmr.57.94 -
Pharmacological Research Jan 2017We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only...
We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system. The protein levels were measured by using western blot techniques. Niclosamide ethanolamine (NEN) treatment relaxed phenylephrine (PE)- and high K (KPSS)-induced constriction, and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE- and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMP-activated protein kinase (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was attenuated in AMPKα1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid and thapsigargin, but not K channel blockers glibenclamide and 5-hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric arteries. NEN treatment increased cytosolic [Ca] and depolarized mitochondrial membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt form showed the similar vasoactivity as NEN in rat mesenteric arteries. Niclosamide ethanolamine inhibits artery constriction, indicating that it would be promising to be developed as an anti-hypertensive drug or it would induce vasodilation-related side effects when absorbed in vivo.
Topics: AMP-Activated Protein Kinases; Animals; Antihypertensive Agents; Aorta; Aorta, Thoracic; Ethanolamine; KATP Channels; Male; Mesenteric Arteries; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Niclosamide; Phenylephrine; Rats; Rats, Sprague-Dawley; Vascular Diseases; Vasoconstriction; Vasodilation; Vasodilator Agents
PubMed: 27872020
DOI: 10.1016/j.phrs.2016.11.008 -
Current Neuropharmacology 2022The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in... (Review)
Review
BACKGROUND
The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in treating neurologic disease. Vasoactive peptides have been shown in animal studies to transiently disrupt the blood-brain barrier and regadenoson is currently being studied in humans to determine if it can improve drug delivery to the brain. However, many other vasoactive peptides could potentially be used for this purpose.
METHODS
We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the blood-brain barrier, we devised a four-tier classification system to organize the available evidence.
RESULTS
We identified 32 vasoactive peptides with potential blood-brain barrier permeabilityaltering properties. To date, none of these are shown to open the blood-brain barrier in humans. Twelve vasoactive peptides increased blood-brain barrier permeability in rodents. The remaining 20 had favorable physiologic effects on blood vessels but lacked specific information on permeability changes to the blood-brain barrier.
CONCLUSION
Vasoactive peptides remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other neurologic diseases. Dozens of vasoactive peptides have yet to be formally evaluated for this important clinical effect. This narrative review summarizes the available data on vasoactive peptides, highlighting agents that deserve further in vitro and in vivo investigations.
Topics: Animals; Blood-Brain Barrier; Central Nervous System; Central Nervous System Agents; Drug Delivery Systems; Humans; Peptides; Proteins
PubMed: 35100958
DOI: 10.2174/1570159X20999220131163504 -
International Journal of Molecular... Aug 2022Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide...
Vasoactive Effects of Chronic Treatment with Fructose and Slow-Releasing HS Donor GYY-4137 in Spontaneously Hypertensive Rats: The Role of Nitroso and Sulfide Signalization.
Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide (HS). We investigated whether a slow-releasing HS donor, GYY-4137, could exert beneficial activity in these conditions. We examined the effect of eight weeks of fructose intake on the blood pressure, biometric parameters, vasoactive responses, and NO and HS pathways in fructose-fed spontaneously hypertensive rats with or without three weeks of GYY-4137 i.p. application. GYY-4137 reduced triacylglycerol levels and blood pressure, but not adiposity, and all were increased by fructose intake. Fructose intake generally enhanced endothelium-dependent vasorelaxation, decreased adrenergic contraction, and increased protein expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and concentration of conjugated dienes in the left ventricle (LV). Although GYY-4137 administration did not affect vasorelaxant responses, it restored disturbed contractility, LV oxidative damage and decreased protein expression of TNFα in fructose-fed rats. While the participation of endogenous HS in vasoactive responses was not affected by fructose treatment, the expression of HS-producing enzyme cystathionine β-synthase in the LV was increased, and the stimulation of the NO signaling pathway improved endothelial function in the mesenteric artery. On the other hand, chronic treatment with GYY-4137 increased the expression of HS-producing enzyme cystathionine γ-lyase in the LV and stimulated the beneficial pro-relaxant and anti-contractile activity of endogenous HS in thoracic aorta. Our results suggest that sulfide and nitroso signaling pathways could trigger compensatory vasoactive responses in hypertensive rats with metabolic disorder. A slow HS-releasing donor could partially amend metabolic-related changes and trigger beneficial activity of endogenous HS.
Topics: Animals; Cystathionine gamma-Lyase; Fructose; Hydrogen Sulfide; Morpholines; Nitric Oxide; Organothiophosphorus Compounds; Rats; Rats, Inbred SHR; Sulfides; Tumor Necrosis Factor-alpha
PubMed: 36012477
DOI: 10.3390/ijms23169215 -
Journal of Biomechanical Engineering Apr 2022Albeit seldom considered explicitly, the vasoactive state of a central artery can contribute to luminal control and thereby affect the in vivo values of flow-induced...
Albeit seldom considered explicitly, the vasoactive state of a central artery can contribute to luminal control and thereby affect the in vivo values of flow-induced wall shear stress and pressure-induced intramural stress, which in turn are strong determinants of wall growth and remodeling. Here, we test the hypothesis that diminished vasoactive capacity compromises effective mechano-adaptations of central arteries. Toward this end, we use consistent methods to re-interpret published data on common carotid artery remodeling in a nonpharmacologic mouse model of induced hypertension and a model of connective tissue disorder that results in Marfan syndrome. The mice have identical genetic backgrounds and, in both cases, the data are consistent with the hypothesis considered. In particular, carotid arteries with strong (normal) vasoactive capacity tend to maintain wall thickness and in vivo axial stretch closer to homeostatic, thus resulting in passive circumferential wall stress and energy storage close to normal. We conclude that effective vasoactivity helps to control the biomechanical state in which the cells and matrix turnover, thus helping to delineate mechano-adaptive from maladaptive remodeling. Future analyses of experimental data and computational models of growth and remodeling should account for this strong coupling between smooth muscle contractile capacity and central arterial remodeling.
Topics: Animals; Carotid Artery, Common; Hypertension; Mice; Muscle Contraction; Muscle, Smooth, Vascular; Stress, Mechanical
PubMed: 34729580
DOI: 10.1115/1.4052888