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Eye (London, England) Apr 2024Amacrine cells (ACs) are the most structurally and functionally diverse neuron type in the retina. Different ACs have distinct functions, such as neuropeptide secretion... (Review)
Review
Amacrine cells (ACs) are the most structurally and functionally diverse neuron type in the retina. Different ACs have distinct functions, such as neuropeptide secretion and inhibitory connection. Vasoactive intestinal peptide (VIP) -ergic -ACs are retina gamma-aminobutyric acid (GABA) -ergic -ACs that were discovered long ago. They secrete VIP and form connections with bipolar cells (BCs), other ACs, and retinal ganglion cells (RGCs). They have a specific structure, density, distribution, and function. They play an important role in myopia, light stimulated responses, retinal vascular disease and other ocular diseases. Their significance in the study of refractive development and disease is increasing daily. However, a systematic review of the structure and function of retinal VIP-ACs is lacking. We discussed the detailed characteristics of VIP-ACs from every aspect across species and providing systematic knowledge base for future studies. Our review led to the main conclusion that retinal VIP-ACs develop early, and although their morphology and distribution across species are not the same, they have similar functions in a wide range of ocular diseases based on their function of secreting neuropeptides and forming inhibitory connections with other cells.
Topics: Humans; Amacrine Cells; Vasoactive Intestinal Peptide; Retina; Retinal Ganglion Cells; gamma-Aminobutyric Acid
PubMed: 38066110
DOI: 10.1038/s41433-023-02844-x -
Frontiers in Cardiovascular Medicine 2023Pharmacological support has become the mainstay therapy in patients with cardiogenic shock (CS). Unfortunately, the clinical benefits of such potent drugs remain...
INTRODUCTION
Pharmacological support has become the mainstay therapy in patients with cardiogenic shock (CS). Unfortunately, the clinical benefits of such potent drugs remain unclear, therefore, the present study aims to elucidate the safety and efficacy of vasoactive agents in CS patients.
METHODS
Medical Information Mart for Intensive Care (MIMIC) IV databases were used for this retrospective study. The primary outcome of this study was 30-day all-cause mortality. The subgroup analysis of was the relationship between the combined use of vasopressors and inotropes and 30-day all-cause mortality.
RESULTS
A total of 2,216 patients diagnosed with CS were enrolled in this study. The non-survivors group was more likely to be older, presented with chronic kidney disease, have a lower systolic blood pressure, lower heart rate, and higher respiratory rate (all < 0.05). In the multivariate Cox regression analysis, only dopamine [HR (95%CI): 1.219 (1.003-1.482)], norepinephrine [HR (95%CI): 2.528 (1.829-3.493)], and milrinone [HR (95%CI): 0.664 (0.512-0.861)] remained an independent predictor for 30-day all-cause mortality. Furthermore, a subgroup analysis was performed and found that no statistically significant difference between no vasopressor/inotrope use and 1 vasopressor/inotrope use ( = 0.107). Meanwhile, a substantial deterioration of cumulative survival was observed when a combination of 2 or more vasopressors/inotropes was used in CS patients in comparison with no vasopressor/inotrope or only 1 vasopressor/inotrope use (all < 0.05).
CONCLUSIONS
Using vasopressors/inotropes agents was associated with a higher risk of 30-day all-cause mortality in CS patients. In addition, only milrinone was associated with a better prognosis among the available vasoactive agents.
PubMed: 38094120
DOI: 10.3389/fcvm.2023.1300839 -
Frontiers in Neuroscience 2023Alzheimer's disease (AD) is the leading cause of dementia, with over 45 million patients worldwide, and poses significant economic and emotional burdens to both patients... (Review)
Review
Alzheimer's disease (AD) is the leading cause of dementia, with over 45 million patients worldwide, and poses significant economic and emotional burdens to both patients and caregivers, significantly raising the number of those affected. Unfortunately, much of the existing research on the disease only addresses a small subset of associated symptomologies and pathologies. In this review, we propose to target the earliest stages of the disease, when symptomology first arises. In these stages, before the onset of hallmark symptoms of AD such as cognitive impairments and memory loss, circadian and olfactory disruptions arise and are detectable. Functional similarities between circadian and olfactory systems provide a basis upon which to seek out common mechanisms in AD which may target them early on in the disease. Existing studies of interactions between these systems, while intriguing, leave open the question of the neural substrates underlying them. Potential substrates for such interactions are proposed in this review, such as indirect projections that may functionally connect the two systems and dopaminergic signaling. These substrates may have significant implications for mechanisms underlying disruptions to circadian and olfactory function in early stages of AD. In this review, we propose early detection of AD using a combination of circadian and olfactory deficits and subsequent early treatment of these deficits may provide profound benefits to both patients and caregivers. Additionally, we suggest that targeting research toward the intersection of these two systems in AD could uncover mechanisms underlying the broader set of symptoms and pathologies that currently elude researchers.
PubMed: 38094003
DOI: 10.3389/fnins.2023.1295998 -
Brain Sciences Nov 2023Aneurysmal subarachnoid hemorrhage (aSAH) provokes a cascade reaction that is responsible for early and delayed brain injuries mediated by intracranial hypertension,... (Review)
Review
Aneurysmal subarachnoid hemorrhage (aSAH) provokes a cascade reaction that is responsible for early and delayed brain injuries mediated by intracranial hypertension, hydrocephalus, cerebral vasospasm (CV), and delayed cerebral ischemia (DCI), which result in increased morbidity and mortality. During open microsurgical repair, cisternal access is achieved essentially to gain proximal vascular control and aneurysm exposition. Cisternostomy also allows brain relaxation, removal of cisternal clots, and restoration of the CSF dynamics through the communication between the anterior and posterior circulation cisterns and the ventricular system, with the opening of the Membrane of Liliequist and lamina terminalis, respectively. Continuous postoperative CSF drainage through a cisternal drain (CD) is a valuable option for treating acute hydrocephalus and intracranial hypertension. Moreover, it efficiently removes the blood and toxic degradation products, with a potential benefit on CV, DCI, and shunt-dependent hydrocephalus. Finally, the CD is an effective pathway to administer vasoactive, fibrinolytic, and anti-oxidant agents and shows promising results in decreasing CV and DCI rates while minimizing systemic effects. We performed a comprehensive review to establish the adjuvant role of cisternostomy and CD performed in cases of direct surgical repair for ruptured intracranial aneurysms and their role in the prevention and treatment of aSAH complications.
PubMed: 38002540
DOI: 10.3390/brainsci13111580 -
Journal of Clinical GastroenterologyProkinetics and proton pump inhibitors are first-line drugs for functional dyspepsia (FD) patients. However, no available treatment is effective for most FD patients,...
BACKGROUND AND AIMS
Prokinetics and proton pump inhibitors are first-line drugs for functional dyspepsia (FD) patients. However, no available treatment is effective for most FD patients, and the pathogenesis is still unclear. The purpose of this study was to investigate the therapeutic effect of transcutaneous neuromodulation (TN) on FD and its potential mechanisms.
MATERIALS AND METHODS
Fifty-seven FD patients were enrolled in the study and randomly divided into 3 groups (TN Neiguan (PC6) group, TN Zusanli (ST36) group, and sham TN group) that received corresponding treatment respectively for 4 weeks. Then, all the patients enrolled received TN PC6 combined with ST36 treatment for another 4 weeks. Dyspepsia symptom questionnaire, Medical outcomes study item short form health survey (SF-36), Hospital Anxiety and Depression Scale were used to assess the severity of symptoms. Gastric accommodation, gastric emptying rate, and related parameters of electrogastrogram were used to assess the pathophysiological mechanism of FD. The possible gastrointestinal hormonal mechanism involved was assessed by detecting serum ghrelin, neuropeptide Y, and vasoactive intestinal peptide. The possible duodenal inflammation mechanism involved was assessed by detecting duodenal mucosa.
RESULTS
TN treatment reduced the dyspepsia symptom score ( P <0.05) and improved the quality of life. After TN treatment, the gastric accommodation ( P <0.01), the gastric emptying rate ( P <0.01), and the percentages of preprandial ( P <0.05) and postprandial ( P <0.05) gastric slow waves (GSW) were increased. The proportions of preprandial ( P <0.05) and postprandial ( P <0.05) gastric electrical rhythm disorder were reduced. The double acupoint combination therapy further enhanced the therapeutic effect of single acupoint. In addition, the levels of ghrelin ( P <0.001) and neuropeptide Y ( P <0.001) were significantly increased, the level of vasoactive intestinal peptide ( P <0.001) was significantly decreased, and the total number of mast cells ( P <0.001) in the duodenal bulb was significantly decreased after double acupoints combination therapy.
CONCLUSIONS
TN treatment significantly improves the dyspepsia symptoms of FD patients and their quality of life. TN treatment increases the percentage of normal GSW, reduces the proportion of gastric electrical rhythm disorder, and improves the gastric accommodation and gastric emptying rate. The therapeutic effect of TN may be caused by regulating gastrointestinal hormone secretion and alleviating local inflammatory responses in duodenum. In addition, the improvement of TN on GSW was closely related to the decrease of bradygastria.
PubMed: 36226998
DOI: 10.1097/MCG.0000000000001775 -
Systematic Reviews Jan 2024The objective of this study is to conduct a systematic review and meta-analysis examining the relationship between the vasoactive-inotropic score (VIS) and patient... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The objective of this study is to conduct a systematic review and meta-analysis examining the relationship between the vasoactive-inotropic score (VIS) and patient outcomes in surgical settings.
METHODS
Two independent reviewers searched PubMed, Web of Science, EMBASE, Scopus, Cochrane Library, Google Scholar, and CNKI databases from November 2010, when the VIS was first published, to December 2022. Additional studies were identified through hand-searching the reference lists of included studies. Eligible studies were those published in English that evaluated the association between the VIS and short- or long-term patient outcomes in both pediatric and adult surgical patients. Meta-analysis was performed using RevMan Manager version 5.3, and quality assessment followed the Joanna Briggs Institute (JBI) Critical Appraisal Checklists.
RESULTS
A total of 58 studies comprising 29,920 patients were included in the systematic review, 34 of which were eligible for meta-analysis. Early postoperative VIS was found to be associated with prolonged mechanical ventilation (OR 5.20, 95% CI 3.78-7.16), mortality (OR 1.08, 95% CI 1.05-1.12), acute kidney injury (AKI) (OR 1.26, 95% CI 1.13-1.41), poor outcomes (OR 1.02, 95% CI 1.01-1.04), and length of stay (LOS) in the ICU (OR 3.50, 95% CI 2.25-5.44). The optimal cutoff value for the VIS as an outcome predictor varied between studies, ranging from 10 to 30.
CONCLUSION
Elevated early postoperative VIS is associated with various adverse outcomes, including acute kidney injury (AKI), mechanical ventilation duration, mortality, poor outcomes, and length of stay (LOS) in the ICU. Monitoring the VIS upon return to the Intensive Care Unit (ICU) could assist medical teams in risk stratification, targeted interventions, and parent counseling.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022359100.
Topics: Adult; Child; Humans; Acute Kidney Injury; Checklist; Databases, Factual; Intensive Care Units; Length of Stay; General Surgery; Patient Outcome Assessment
PubMed: 38184601
DOI: 10.1186/s13643-023-02403-1 -
The Journal of Neuroscience : the... Nov 2023Attention deficit is one of the most prominent and disabling symptoms in Fragile X syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention...
Attention deficit is one of the most prominent and disabling symptoms in Fragile X syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in humans and mice with FXS but not in typically developing controls. In both species, males and females were examined. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the poststimulus period during early distractor trials in WT mice, consistent with their known role as error signals. Strikingly, however, VIP cells from mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells could be a potential therapeutic target for attentional difficulties in FXS. Sensory hypersensitivity, impulsivity, and persistent inattention are among the most consistent clinical features of FXS, all of which impede daily functioning and create barriers to learning. However, the neural mechanisms underlying sensory over-reactivity remain elusive. To overcome a significant challenge in translational FXS research we demonstrate a compelling alignment of sensory over-reactivity in both humans with FXS and mice (the principal animal model of FXS) using a novel analogous distractor task. Two-photon microscopy in mice revealed that lack of modulation by VIP cells contributes to susceptibility to distractors. Implementing research efforts we describe here can help identify dysfunctional neural mechanisms associated not only with sensory issues but broader impairments, including those in learning and cognition.
Topics: Humans; Male; Female; Animals; Mice; Vasoactive Intestinal Peptide; Fragile X Syndrome; Fragile X Mental Retardation Protein; Activities of Daily Living; Interneurons; Mice, Knockout; Disease Models, Animal
PubMed: 37816596
DOI: 10.1523/JNEUROSCI.0571-23.2023 -
Circulation Research Sep 2023The phrase complete vagal withdrawal is often used when discussing autonomic control of the heart during exercise. However, more recent studies have challenged this...
BACKGROUND
The phrase complete vagal withdrawal is often used when discussing autonomic control of the heart during exercise. However, more recent studies have challenged this assumption. We hypothesized that cardiac vagal activity increases during exercise and maintains cardiac function via transmitters other than acetylcholine.
METHODS
Chronic direct recordings of cardiac vagal nerve activity, cardiac output, coronary artery blood flow, and heart rate were recorded in conscious adult sheep during whole-body treadmill exercise. Cardiac innervation of the left cardiac vagal branch was confirmed with lipophilic tracer dyes (DiO). Sheep were exercised with pharmacological blockers of acetylcholine (atropine, 250 mg), VIP (vasoactive intestinal peptide; [4Cl-D-Phe6,Leu17]VIP 25 µg), or saline control, randomized on different days. In a subset of sheep, the left cardiac vagal branch was denervated.
RESULTS
Neural innervation from the cardiac vagal branch is seen at major cardiac ganglionic plexi, and within the fat pads associated with the coronary arteries. Directly recorded cardiac vagal nerve activity increased during exercise. Left cardiac vagal branch denervation attenuated the maximum changes in coronary artery blood flow (maximum exercise, control: 63.5±5.9 mL/min, n=8; cardiac vagal denervated: 32.7±5.6 mL/min, n=6, 2.5×10), cardiac output, and heart rate during exercise. Atropine did not affect any cardiac parameters during exercise, but VIP antagonism significantly reduced coronary artery blood flow during exercise to a similar level to vagal denervation.
CONCLUSIONS
Our study demonstrates that cardiac vagal nerve activity actually increases and is crucial for maintaining cardiac function during exercise. Furthermore, our findings show the dynamic modulation of coronary artery blood flow during exercise is mediated by VIP.
Topics: Animals; Sheep; Acetylcholine; Heart; Coronary Vessels; Cardiac Output; Atropine
PubMed: 37641938
DOI: 10.1161/CIRCRESAHA.123.323017 -
International Immunopharmacology Sep 2023Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA)....
Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA). Targeting inflammatory pathways is an important therapeutic strategy for OA. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide with potent anti-inflammatory effects; however, its role and mechanism in OA remain unclear. In this study, microarray expression profiling from the Gene Expression Omnibus database and integrative bioinformatics analyses were performed to identify differentially expressed lncRNAs in OA samples. qRT-PCR validation of the top ten different expressed lncRNAs indicated that the expression level of intergenic non-protein coding RNA 2203 (LINC02203, also named LOC727924) was the highest in OA cartilage compared to normal cartilage. Hence, the LOC727924 function was further investigated. LOC727924 was upregulated in OA chondrocytes, with a dominant sub-localization in the cytoplasm. In OA chondrocytes, LOC727924 knockdown boosted cell viability, suppressed cell apoptosis, reactive oxygen species (ROS) accumulation, increased aggrecan and collagen II, decreased matrix metallopeptidase (MMP)-3/13 and ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4/5 levels, and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). LOC727924 could interact with the microRNA 26a (miR-26a)/ karyopherin subunit alpha 3 (KPNA3) axis by competitively targeting miR-26a for KPNA3 binding, therefore down-regulating miR-26a and upregulating KPNA3; in OA chondrocytes, miR-26a inhibition partially abolished LOC727924 knockdown effects on chondrocytes. miR-26a inhibited the nuclear translocation of p65 through targeting KPNA3 and p65 transcriptionally activated LOC727924, forming a p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop to modulate OA chondrocyte phenotypes. In vitro, VIP improved OA chondrocyte proliferation and functions, down-regulated LOC727924, KPNA3, and p65 expression, and upregulated miR-26a expression; in vivo, VIP ameliorated destabilization of the medial meniscus (DMM)-induced damages on the mouse knee joint, down-regulated KPNA3, inhibited the nuclear translocation of p65. In conclusion, the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates OA chondrocyte apoptosis, ROS accumulation, extracellular matrix (ECM) deposition, and inflammatory response in vitro and OA development in vivo, being one of the mechanisms mediating VIP ameliorating OA.
Topics: Mice; Animals; MicroRNAs; Chondrocytes; Vasoactive Intestinal Peptide; RNA, Long Noncoding; Reactive Oxygen Species; Cartilage, Articular; Osteoarthritis; Interleukin-1beta; Apoptosis
PubMed: 37392568
DOI: 10.1016/j.intimp.2023.110518 -
Current Opinion in Nephrology and... Mar 2024The transmembrane protein 16A (TMEM16A) Ca 2+ -activated Cl - channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while... (Review)
Review
PURPOSE OF REVIEW
The transmembrane protein 16A (TMEM16A) Ca 2+ -activated Cl - channel constitutes a key depolarising mechanism in vascular smooth muscle and contractile pericytes, while in endothelial cells the channel is implicated in angiogenesis and in the response to vasoactive stimuli. Here, we offer a critical analysis of recent physiological investigations and consider the potential for targeting TMEM16A channels in vascular disease.
RECENT FINDINGS
Genetic deletion or pharmacological inhibition of TMEM16A channels in vascular smooth muscle decreases artery tone and lowers systemic blood pressure in rodent models. Inhibition of TMEM16A channels in cerebral cortical pericytes protects against ischemia-induced tissue damage and improves microvascular blood flow in rodent stroke models. In endothelial cells, the TMEM16A channel plays varied roles including modulation of cell division and control of vessel tone through spread of hyperpolarisation to the smooth muscle cells. Genetic studies implicate TMEM16A channels in human disease including systemic and pulmonary hypertension, stroke and Moyamoya disease.
SUMMARY
The TMEM16A channel regulates vascular function by controlling artery tone and capillary diameter as well as vessel formation and histology. Preclinical and clinical investigations are highlighting the potential for therapeutic exploitation of the channel in a range of maladaptive states of the (micro)circulation.
Topics: Humans; Chloride Channels; Endothelial Cells; Hypertension, Pulmonary; Myocytes, Smooth Muscle; Stroke
PubMed: 38193301
DOI: 10.1097/MNH.0000000000000967