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Frontiers in Molecular Neuroscience 2024Dm9 neurons in have been proposed as functional homologs of horizontal cells in the outer retina of vertebrates. Here we combine genetic dissection of neuronal circuit...
Dm9 neurons in have been proposed as functional homologs of horizontal cells in the outer retina of vertebrates. Here we combine genetic dissection of neuronal circuit function, two-photon calcium imaging in Dm9 and inner photoreceptors, and immunohistochemical analysis to reveal novel insights into the functional role of Dm9 in early visual processing. Our experiments show that Dm9 receive input from all four types of inner photoreceptor R7p, R7y, R8p, and R8y. Histamine released from all types R7/R8 directly inhibits Dm9 via the histamine receptor Ort, and outweighs simultaneous histamine-independent excitation of Dm9 by UV-sensitive R7. Dm9 in turn provides inhibitory feedback to all R7/R8, which is sufficient for color-opponent processing in R7 but not R8. Color opponent processing in R8 requires additional synaptic inhibition by R7 of the same ommatidium via axo-axonal synapses and the second histamine receptor HisCl1. Notably, optogenetic inhibition of Dm9 prohibits color opponent processing in all types of R7/R8 and decreases intracellular calcium in photoreceptor terminals. The latter likely results from reduced release of excitatory glutamate from Dm9 and shifts overall photoreceptor sensitivity toward higher light intensities. In summary, our results underscore a key role of Dm9 in color opponent processing in and suggest a second role of Dm9 in regulating light adaptation in inner photoreceptors. These novel findings on Dm9 are indeed reminiscent of the versatile functions of horizontal cells in the vertebrate retina.
PubMed: 38813436
DOI: 10.3389/fnmol.2024.1347540 -
Cureus Apr 2024Ayurveda, an ancient Indian system of medicine, encapsulates comprehensive principles and formulations for disease prevention and treatment. A herbo-mineral Ayurvedic...
BACKGROUND
Ayurveda, an ancient Indian system of medicine, encapsulates comprehensive principles and formulations for disease prevention and treatment. A herbo-mineral Ayurvedic formulation, IMMBO, comprising and 18 herbs has shown promising results in treating allergic rhinitis in clinical studies.
OBJECTIVE
This discussed series of experimental studies were conducted to explore the immuno-modulatory potential of IMMBO.
METHODOLOGY
A series of experimental studies were carried out in immunosuppressed rats to explore the immune-modulatory effects of IMMBO.
RESULTS
IMMBO was effective in reinstating neutrophil activation, stimulating cellular and humoral immunity, and counteracting immunosuppression at the molecular level. The modulation of key signalling molecules, including tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-1 beta (IL-1β), extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), and nuclear factor-kappa B (NF-κb), showcased the formulation's multifaceted impact. Additionally, its ability to block histamine release suggests potential in controlling allergic states, positioning it as a promising therapeutic candidate for immune-related disorders. However, the precise mode of action remains elusive, warranting further in-depth pharmacological studies.
CONCLUSION
This research substantiates the ancient Ayurvedic wisdom using modern scientific parameters, endorsing IMMBO's potential as an immune-modulatory agent.
PubMed: 38800281
DOI: 10.7759/cureus.58913 -
Animals : An Open Access Journal From... May 2024The ecosystem of ruminal microbiota profoundly affects the health and milk production of dairy cows. High-concentrate diets are widely used in dairy farms and evoke a...
The ecosystem of ruminal microbiota profoundly affects the health and milk production of dairy cows. High-concentrate diets are widely used in dairy farms and evoke a series of metabolic disorders. Several studies have reported the effects of high-concentrate diets on the ruminal microbiome, while the effect of changes in ruminal microbial flora, induced by high-concentrate diet feeding, on the liver of dairy cows has not been studied before. In this study, 12 mid-lactating Holstein Friesian cows (weight of 455 ± 28 kg; parities of 2.5 ± 0.5; starting milk yield of 31.59 ± 3.2 kg/d; DMI of 21.7 ± 1.1 kg/d; and a DIM at the start of the experiment of 135 ± 28 d) were fitted with ruminal fistulas, as well as with portal and hepatic vein catheters. All cows were randomly divided into 2 groups; then, they fed with low-concentrate diets (LC, concentrate: forage = 40:60) and high-concentrate diets (HC, concentrate: forage = 60:40) for 18 weeks. The forage sources were corn silage and alfalfa hay. After the cows of two groups were euthanized over two consecutive days, ruminal microbiota; the concentration of LPS in the rumen content; cecum content; the levels of blood and histamine in rumen fluid, blood, and the liver; the histopathological status of the rumen and cecum; and the inflammatory response of the liver were assessed in dairy cows under conditions of subacute ruminal acidosis (SARA). These conditions were caused by high-concentrate diet feeding. All data were analyzed using the independent -test in SPSS. The results showed that high-concentrate diet feeding increased the concentration of LPS and histamine in the rumen and plasma of veins ( < 0.05). The abundance of at the phylum level, and of both and at the genus level, was decreased, while the abundance of at the phylum level and at the genus level was increased by high-concentrate diet feeding. The decreased pH values of ruminal contents (LC = 6.02, HC = 5.90, < 0.05) and the increased level of LPS in the rumen (LC = 4.921 × 10, HC = 7.855 × 10 EU/mL, < 0.05) and cecum (LC = 11.960 × 10, HC = 13.115 × 10 EU/mL, < 0.01) induced the histopathological destruction of the rumen and cecum, combined with the increased mRNA expression of IL-1β ( < 0.05). The histamine receptor H1R and the NF-κB signaling pathway were activated in the liver samples taken from the HC group. In conclusion, the elevated concentrations of LPS and histamine in the gut may be related to changes in the ruminal microbiota. LPS and histamine induced the inflammatory response in the ruminal epithelium, cecum epithelium, and liver. However, the cause-effect mechanism needs to be proved in future research. Our study offers a novel therapeutic strategy by manipulating ruminal microbiota and metabolism to decrease LPS and histamine release and to improve the health of dairy cows.
PubMed: 38791713
DOI: 10.3390/ani14101495 -
AJP Reports Apr 2024Superoxide anions (O ) have multiple effects on pulmonary parenchyma altering cell proliferation, cellular metabolism, and airway smooth muscle (ASM) contraction....
Superoxide anions (O ) have multiple effects on pulmonary parenchyma altering cell proliferation, cellular metabolism, and airway smooth muscle (ASM) contraction. Intracellular calcium ([Ca ] ) concentration plays a significant role in the regulation of ASM contraction, relaxation, proliferation, and gene expression. We investigated the effects of O on agonist-stimulated changes in [Ca ] in ASM cells. Fura-2 AM-loaded, freshly isolated porcine ASM (PASM) cells were used to examine [Ca ] release in response to acetylcholine (ACh), histamine, endothelin, caffeine, and thapsigargin (TPG) in the presence or absence of extracellular Ca . Exposure of PASM cells to xanthine and xanthine oxidase (X + XO) resulted in a time-dependent generation of O , inhibited by superoxide dismutase (SOD). Preincubating PASM cells with X + XO for 15- or 45-minute inhibited net [Ca ] responses to ACh, histamine, caffeine, and TPG compared with control cells. Pretreating PASM cells with SOD for 30 minutes mitigated the inhibitory effect of X + XO treatment on ACh-induced Ca elevation suggesting role of O . X + XO treatment also inhibited caffeine- and TPG-induced Ca elevation suggesting effect of O on [Ca ] release and reuptake mechanisms. Superoxide attenuates [Ca ] release, reuptake, and may interfere with physiological functions of ASM cells.
PubMed: 38784940
DOI: 10.1055/a-2318-0625 -
BioRxiv : the Preprint Server For... May 2024Mast cells are innate immune cells that play a crucial role in numerous physiological processes across tissues by releasing pre-stored and newly synthesized mediators in...
Mast cells are innate immune cells that play a crucial role in numerous physiological processes across tissues by releasing pre-stored and newly synthesized mediators in response to stimuli, an activity largely driven by changes in gene expression. Given their widespread influence, dysfunction in mast cells can contribute to a variety of pathologies including allergies, long COVID, and autoimmune and neuroinflammatory disorders. Despite this, the specific transcriptional mechanisms that control mast cell mediator release remain poorly understood, significantly hindering the development of effective therapeutic strategies. We found that the two proteins encoded by the transcription factor FosB, FOSB and the highly stable variant ΔFOSB, are robustly expressed upon stimulation in both murine and human mast cell progenitors. Motivated by these findings, we generated a novel mouse model with targeted ablation of FosB gene expression specifically in mast cells (MC ) by crossing a mast cell-specific Cre reporter line (Mcpt5-Cre) with a Cre-dependent floxed FosB mouse lines. We found that mast cell progenitors derived from MC mice, compared to wild types (WT), exhibit baseline increased histamine content and vesicle numbers. Additionally, they show enhanced calcium mobilization, degranulation, and histamine release following allergy-related IgE-mediated stimulation, along with heightened IL-6 release in response to infection-like LPS stimulation. experiments with IgE- mediated and LPS challenges revealed that MC mice experience greater drops in body temperature, heightened activation of tissue-resident mast cells, and increased release of pro-inflammatory mediators compared to their WT counterparts. These findings suggest that FosB products play a crucial regulatory role in moderating stimulus-induced mast cell activation in response to both IgE and LPS stimuli. Lastly, by integrating CUT&RUN and RNAseq data, we identified several genes targeted by ΔFOSB that could mediate these observed effects, including Mir155hg, CLCF1, DUSP4, and Trib1. Together, this study provides the first evidence that FOSB/ΔFOSB modulate mast cell functions and provides a new possible target for therapeutic interventions aimed at ameliorating mast cell-related diseases.
PubMed: 38766119
DOI: 10.1101/2024.05.06.592755 -
Biomedical Reports Jun 2024In Taiwan, the use of radiocontrast medium for clinical image diagnosis recently surpassed one million times and the overall prevalence of radiocontrast hypersensitivity...
In Taiwan, the use of radiocontrast medium for clinical image diagnosis recently surpassed one million times and the overall prevalence of radiocontrast hypersensitivity was ~7%. A microRNA (miRNA/miRs) is a small non-coding RNA molecule that mostly plays a suppressor role in cells. However, the roles of miRNA expression in radiocontrast-induced mast cells activation remains to be elucidated. The aim of the present study was to investigate the role of miRNA on radiocontrast-induced mast cell activation. Computed tomography radiocontrast, ultravist and mouse mast cell line, P815, were used in the present study. Cell viability was detected by CCK-8 experiment. Levels of histamine and β-hexosaminidase were measured by ELISA. miRNA expression was detected by miRNA sequencing and reverse transcription-quantitative PCR. The results showed that ultravist could increase histamine release and reduce intracellular β-hexosaminidase levels of mast cells. A total of 102 miRNAs could be significantly upregulated by ultravist stimulation. Selected candidate miRNAs for the validation included miR-19a-3p and miR-362-3p which were also increased expression following stimulation with ultravist. In conclusion, ultravist could induce mast cell activation through upregulation of miR-19a-3p and miR-362-3p. Thus, miR-19a-3p and miR-362-3p could be promising candidates for development as novel targets for preventing radiocontrast-induced allergy in the future.
PubMed: 38765857
DOI: 10.3892/br.2024.1780 -
Skin Research and Technology : Official... May 2024Urticaria is a prevalent recurrent skin allergic condition. Severe itching significantly impacts patients' quality of life. This paper aims to investigate the...
BACKGROUND AND PURPOSE
Urticaria is a prevalent recurrent skin allergic condition. Severe itching significantly impacts patients' quality of life. This paper aims to investigate the development status of urticaria through bibliometric analysis to predict future research hotspots and trends.
METHODS
On October 29, 2023, a literature search was conducted in the Web of Science (WOS) database to collect urticaria-related publications. The top 100 most cited articles were charted, and VOSviewer software was utilized for the literature data analysis. A visual analysis was performed on the number of articles, journals, main researchers, keywords, and so on.
RESULTS
The research involved 415 authors from 28 countries, published across 25 journals, ranging from 1963 to 2023. Marcus Maurer was the leading author, with the United States being the foremost country in urticaria research. CEH Grattan received the most citations, and The Medical University of South Carolina had the highest number of publications. Key research focuses include epidemiology, pathogenesis, drug therapy, and quality of life assessments. "Anti-high affinity IgE receptor α chain (FcεRIα)," "chronic idiopathic urticaria," "autoantibodies," "histamine-release" emerged as the keywords with the highest prominence.
CONCLUSION
The field of urticaria research has attracted substantial attention over the past few decades, witnessing rapid development. This study highlighted the top 100 articles by citation frequency within the urticaria field. Bibliometric analysis revealed a shift in treatment methods from traditional antihistamines to biological agents, with significant emphasis on improving the quality of life in chronic urticaria management. These areas represent the current research focal points and indicate future trends in urticaria research.
Topics: Bibliometrics; Humans; Urticaria; Quality of Life; Biomedical Research
PubMed: 38747942
DOI: 10.1111/srt.13731 -
Cureus Apr 2024Background General anaesthesia (GA) is predominantly important for conducting tracheal intubation; it should be quick and precise, having a prudent performance. It is...
Background General anaesthesia (GA) is predominantly important for conducting tracheal intubation; it should be quick and precise, having a prudent performance. It is preferable to use a neuromuscular blocking drug, which ideally should be highly potent, with a rapid onset and a short duration clinical effect in order to prevent the development of hypoxia during laryngoscopy and tracheal intubation and also avoid any changes in haemodynamics caused by the release of histamine, ganglion block, and anti-muscarinic actions. The non-depolarizing muscle relaxants rocuronium and cisatracurium don't have any noticeable independent side effects when used within the recommended dosage levels. Aim The aim was to compare the clinical efficacy of rocuronium bromide and cisatracurium besylate with respect to their property as muscle relaxants in producing favourable intubating conditions and to assess their haemodynamic stability. The objectives of the study were to evaluate the onset of action and any undesirable effects. Methods Between the ages of 20 to 60 years, 60 patients of either gender, divided randomly into groups of 30 each, of American Society of Anesthesiologists (ASA) physical status classification I and II, were put for elective surgical procedures to be done under general anaesthesia. Patients were given 0.6 mg kg-1 IV of rocuronium in Group R and 0.15 mg kg-1 IV of cisatracurium in Group C. After injecting the muscle relaxants, parameters were measured 60, 90, 120, 150, 180, 240, and 300 seconds later. Result Demographical variables like age, gender, and ASA physical status of the two groups were analogous. Group R had good to excellent/favourable intubating conditions by 90 seconds, and Group C by 240 seconds with comparable haemodynamic stability. The onset of action was significantly faster in Group R (92 ± 7.61 seconds) than in Group C (188 ± 40.88 seconds). Conclusion Rocuronium produced favourable intubating conditions having good haemodynamic stability and a statistically significant (p < 0.00001) faster onset of action in comparison to cisatracurium.
PubMed: 38725766
DOI: 10.7759/cureus.57878 -
American Journal of Veterinary Research Jun 2024To examine the potential of galangin in a mouse model of ovalbumin (OVA)-induced allergic rhinitis (AR), as chronic AR, induced by immunoglobulin-E (IgE), leads to...
OBJECTIVE
To examine the potential of galangin in a mouse model of ovalbumin (OVA)-induced allergic rhinitis (AR), as chronic AR, induced by immunoglobulin-E (IgE), leads to histamine release and nasal inflammation, and although galangin exhibits antiasthmatic and anti-inflammatory potential, its effect on AR is yet to be investigated.
ANIMALS
126 BALB/c mice.
METHODS
AR induction involved sensitizing female mice with OVA (5%, 500 µL, IP) for 14 days. Post OVA challenge, the mice were divided into 7 groups (n = 18/group), including normal, AR control, montelukast (10 mg/kg), galangin (5, 10, and 20 mg/kg), and per se (galangin [20 mg/kg] treatment. Various outcomes were evaluated, including nasal symptoms, histopathology, biochemistry, and nasal lavage fluid inflammatory cytokines and signaling pathways in nasal mucosal to assess galangin potential in AR.
RESULTS
In AR mice, galangin (10 and 20 mg/kg) significantly (P < .05) reduced sneezing, rubbing, and nasal discharge post-OVA challenge. Galangin treatment attenuated (P < .05) elevated serum histamine, β-hexosaminidase, IgE, and Immunoglobulin G1 levels in AR control mice. Additionally, galangin significantly (P < .05) decreased OVA-induced alterations in IL-4, IL-6, IL-13, and interferon-γ levels in nasal lavage fluid compared to AR control mice. Western blot analysis demonstrated that galangin lowered OVA-induced AR by significantly (P < .05) downregulating the phosphorylated protein kinase B and mammalian target of rapamycin-protein expressions while markedly (P < .05) upregulating the glycogen synthase kinase-3β protein expressions in nasal mucosal. Galangin also significantly ameliorated (P < .05) the OVA-induced histological aberrations in the nasal mucosa, reflected by reduced eosinophil infiltration, hyperplasia, and edema.
CLINICAL RELEVANCE
Galangin exhibits antihistaminic and anti-inflammatory effects in AR mice by regulating IgE-mediated histamine and inflammatory release and modulating the phosphatidylinositol 3-kinase/Ak strain transforming/mammalian target of rapamycin pathways.
Topics: Animals; Ovalbumin; Mice, Inbred BALB C; Flavonoids; Mice; Female; Rhinitis, Allergic; Phosphatidylinositol 3-Kinases; Signal Transduction; Proto-Oncogene Proteins c-akt; Disease Models, Animal; Quinolines; Cytokines; Nasal Mucosa; Immunoglobulin E; Acetates; Cyclopropanes; Sulfides
PubMed: 38697189
DOI: 10.2460/ajvr.24.02.0031