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Frontiers in Immunology 2024Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1... (Review)
Review
Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is one such clinical entity. In this paper, we explore the existing evidence that mast cells (MCs) degranulation may contribute to the activation of the kallikrein-kinin system cascade, followed by bradykinin formation and angioedema. We present the multidirectional effects of MC-derived heparin and other polyanions on the major components of the kinin-kallikrein system, particularly on the factor XII activation. Although, bradykinin- and histamine-mediated symptoms are distinct clinical phenomena, they share some common features, such as some similar triggers and a predilection to occur at sites where mast cells reside, namely the skin and mucous membranes. In addition, recent observations indicate a high incidence of hypersensitivity reactions associated with MC degranulation in the HAE-C1-INH patient population. However, not all of these can be explained by IgE-dependent mechanisms. Mast cell-related G protein-coupled receptor-X2 (MRGPRX2), which has recently attracted scientific interest, may be involved in the activation of MCs through a different pathway. Therefore, we reviewed MRGPRX2 ligands that HAE-C1-INH patients may be exposed to in their daily lives and that may affect MCs degranulation. We also discussed the known inter- and intra-individual variability in the course of HAE-C1-INH in relation to factors responsible for possible variability in the strength of the response to MRGPRX2 receptor stimulation. The above issues raise several questions for future research. It is not known to what extent a prophylactic or therapeutic intervention targeting the pathways of one mechanism (mast cell degranulation) may affect the other (bradykinin production), or whether the number of mast cells at a specific body site and their reactivity to triggers such as pressure, allergens or MRGPRX2 agonists may influence the occurrence of HAE-C1-INH attacks at that site.
Topics: Humans; Mast Cells; Cell Degranulation; Bradykinin; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Animals; Angioedema; Nerve Tissue Proteins; Kallikrein-Kinin System
PubMed: 38812508
DOI: 10.3389/fimmu.2024.1399459 -
European Journal of Medical Research May 2024Previously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel...
Identifying novel clinical phenotypes of acute respiratory distress syndrome using trajectories of daily fluid balance: a secondary analysis of randomized controlled trials.
BACKGROUND
Previously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel clinical phenotypes in ARDS using trajectories of fluid balance, to test whether phenotypes respond differently to different treatment, and to develop a simplified model for phenotype identification.
METHODS
FACTT (conservative vs liberal fluid management) trial was classified as a development cohort, joint latent class mixed models (JLCMMs) were employed to identify trajectories of fluid balance. Heterogeneity of treatment effect (HTE) for fluid management strategy across phenotypes was investigated. We also constructed a parsimonious probabilistic model using baseline data to predict the fluid trajectories in the development cohort. The trajectory groups and the probabilistic model were externally validated in EDEN (initial trophic vs full enteral feeding) trial.
RESULTS
Using JLCMM, we identified two trajectory groups in the development cohort: Class 1 (n = 758, 76.4% of the cohort) had an early positive fluid balance, but achieved negative fluid balance rapidly, and Class 2 (n = 234, 24.6% of the cohort) was characterized by persistent positive fluid balance. Compared to Class 1 patients, patients in Class 2 had significantly higher 60-day mortality (53.5% vs. 17.8%, p < 0.001), and fewer ventilator-free days (0 vs. 20, p < 0.001). A significant HTE between phenotypes and fluid management strategies was observed in the FACTT. An 8-variables model was derived for phenotype assignment.
CONCLUSIONS
We identified and validated two novel clinical trajectories for ARDS patients, with both prognostic and predictive enrichment. The trajectories of ARDS can be identified with simple classifier models.
Topics: Humans; Respiratory Distress Syndrome; Female; Phenotype; Male; Middle Aged; Fluid Therapy; Water-Electrolyte Balance; Randomized Controlled Trials as Topic; Aged
PubMed: 38807163
DOI: 10.1186/s40001-024-01866-9 -
Antioxidants (Basel, Switzerland) Apr 2024Rice ( L.) is one of the most important food crops worldwide. However, during direct seeding, rice is extremely vulnerable to flooding stress, which impairs rice's...
Rice ( L.) is one of the most important food crops worldwide. However, during direct seeding, rice is extremely vulnerable to flooding stress, which impairs rice's emergence and seedling growth and results in a significant yield loss. According to our research, chitosan oligosaccharides have the potential to be a chemical seed-soaking agent that greatly increases rice's resistance to flooding. Chitosan oligosaccharides were able to enhance seed energy supply, osmoregulation, and antioxidant capacity, according to physiological index assessments. Using transcriptome and metabolomic analysis, we discovered that important differential metabolites and genes were involved in the signaling pathway for hormone synthesis and antioxidant capacity. Exogenous chitosan oligosaccharides specifically and significantly inhibit genes linked to auxin, jasmonic acid, and abscisic acid. This suggested that applying chitosan oligosaccharides could stabilize seedling growth and development by controlling associated hormones and reducing flooding stress by enhancing membrane stability and antioxidant capacity. Finally, we verified the effectiveness of exogenous chitosan oligosaccharides imbibed in seeds by field validation, demonstrating that they can enhance rice seedling emergence and growth under flooding stress.
PubMed: 38790626
DOI: 10.3390/antiox13050521 -
Plant Physiology and Biochemistry : PPB May 2024Ginseng frequently encounters environmental stress during its growth and development. Late Embryogenesis Abundant (LEA) proteins play a crucial role in combating...
Ginseng frequently encounters environmental stress during its growth and development. Late Embryogenesis Abundant (LEA) proteins play a crucial role in combating adversity stress, particularly against abiotic challenges In this study, 107 LEA genes from ginseng, spanning eight subfamilies, were identified, demonstrating significant evolutionary conservation, with the LEA2 subfamily being most prominent. Gene duplication events, primarily segmental duplications, have played a major role in the expansion of the LEA gene family, which has undergone strong purifying selection. PgLEAs were unevenly distributed across 22 chromosomes, with each subfamily featuring unique structural domains and conserved motifs. PgLEAs were expressed in various tissues, exhibiting distinct variations in abundance and tissue specificity. Numerous regulatory cis-elements, related to abiotic stress and hormones, were identified in the promoter region. Additionally, PgLEAs were regulated by a diverse array of abiotic stress-related transcription factors. A total of 35 PgLEAs were differentially expressed following treatments with ABA, GA, and IAA. Twenty-three PgLEAs showed significant but varied responses to drought, extreme temperatures, and salinity stress. The transformation of tobacco with the key gene PgLEA2-50 enhanced osmoregulation and antioxidant levels in transgenic lines, improving their resistance to abiotic stress. This study offers insights into functional gene analysis, focusing on LEA proteins, and establishes a foundational framework for research on ginseng's resilience to abiotic stress.
PubMed: 38772166
DOI: 10.1016/j.plaphy.2024.108742 -
Skin Research and Technology : Official... May 2024
Topics: Humans; Dermatitis, Atopic; Water Loss, Insensible; Epidermis; Female; Male; Adult; Body Water; Young Adult; Water; Middle Aged
PubMed: 38766887
DOI: 10.1111/srt.13709 -
BioRxiv : the Preprint Server For... May 2024The disruption of calcium signaling associated with polycystin deficiency has been proposed as the primary event underlying the increased abnormally patterned epithelial...
The disruption of calcium signaling associated with polycystin deficiency has been proposed as the primary event underlying the increased abnormally patterned epithelial cell growth characteristic of Polycystic Kidney Disease. Calcium can be regulated through mechanotransduction, and the mechanosensitive cation channel Piezo1 has been implicated in sensing of intrarenal pressure and in urinary osmoregulation. However, a possible role for PIEZO1 in kidney cystogenesis remains undefined. We hypothesized that cystogenesis in ADPKD reflects altered mechanotransduction, suggesting activation of mechanosensitive cation channels as a therapeutic strategy for ADPKD. Here, we show that Yoda-1 activation of PIEZO1 increases intracellular Ca and reduces forskolin-induced cAMP levels in mIMCD3 cells. Yoda-1 reduced forskolin-induced IMCD cyst surface area and in mouse metanephros in a dose-dependent manner. Knockout of polycystin-2 dampened the efficacy of PIEZO1 activation in reducing both cAMP levels and cyst surface area in IMCD3 cells. However, collecting duct-specific knockout neither induced cystogenesis in wild-type mice nor affected cystogenesis in the model of ADPKD. Our study suggests that polycystin-2 and PIEZO1 play a role in mechanotransduction during cystogenesis , and , but that cyst expansion may require inactivation or repression of additional suppressors of cystogenesis and/or growth. Our study provides a preliminary proof of concept for PIEZO1 activation as a possible component of combination chemotherapy to retard or halt cystogenesis and/or cyst growth.
PubMed: 38766249
DOI: 10.1101/2024.05.11.593717 -
BMC Plant Biology May 2024Salinity is one major abiotic stress affecting photosynthesis, plant growth, and development, resulting in low-input crops. Although photosynthesis underlies the...
BACKGROUND
Salinity is one major abiotic stress affecting photosynthesis, plant growth, and development, resulting in low-input crops. Although photosynthesis underlies the substantial productivity and biomass storage of crop yield, the response of the sunflower photosynthetic machinery to salinity imposition and how HS mitigates the salinity-induced photosynthetic injury remains largely unclear. Seed priming with 0.5 mM NaHS, as a donor of HS, was adopted to analyze this issue under NaCl stress. Primed and nonprime seeds were established in nonsaline soil irrigated with tape water for 14 d, and then the seedlings were exposed to 150 mM NaCl for 7 d under controlled growth conditions.
RESULTS
Salinity stress significantly harmed plant growth, photosynthetic parameters, the structural integrity of chloroplasts, and mesophyll cells. HS priming improved the growth parameters, relative water content, stomatal density and aperture, photosynthetic pigments, photochemical efficiency of PSII, photosynthetic performance, soluble sugar as well as soluble protein contents while reducing proline and ABA under salinity. HS also boosted the transcriptional level of ribulose 1,5-bisphosphate carboxylase small subunit gene (HaRBCS). Further, the transmission electron microscope showed that under HS priming and salinity stress, mesophyll cells maintained their cell membrane integrity and integrated chloroplasts with well-developed thylakoid membranes.
CONCLUSION
The results underscore the importance of HS priming in maintaining photochemical efficiency, Rubisco activity, and preserving the chloroplast structure which participates in salinity stress adaptation, and possibly sunflower productivity under salinity imposition. This underpins retaining and minimizing the injury to the photosynthetic machinery to be a crucial trait in response of sunflower to salinity stress.
Topics: Helianthus; Photosynthesis; Seedlings; Salt Stress; Hydrogen Sulfide; Osmoregulation; Chloroplasts; Salinity
PubMed: 38760671
DOI: 10.1186/s12870-024-05071-y -
Frontiers in Endocrinology 2024The brain regulates multiple physiological processes in fish. Despite this, knowledge about the basic structure and function of distinct brain regions in non-model fish...
The brain regulates multiple physiological processes in fish. Despite this, knowledge about the basic structure and function of distinct brain regions in non-model fish species remains limited due to their diversity and the scarcity of common biomarkers. In the present study, four major brain parts, the telencephalon, diencephalon, mesencephalon and rhombencephalon, were isolated in largemouth bass, . Within these parts, nine brain regions and 74 nuclei were further identified through morphological and cytoarchitectonic analysis. Transcriptome analysis revealed a total of 7153 region-highly expressed genes and 176 region-specifically expressed genes. Genes related to growth, reproduction, emotion, learning, and memory were significantly overexpressed in the olfactory bulb and telencephalon (OBT). Feeding and stress-related genes were in the hypothalamus (Hy). Visual system-related genes were predominantly enriched in the optic tectum (OT), while vision and hearing-related genes were widely expressed in the cerebellum (Ce) region. Sensory input and motor output-related genes were in the medulla oblongata (Mo). Osmoregulation, stress response, sleep/wake cycles, and reproduction-related genes were highly expressed in the remaining brain (RB). Three candidate marker genes were further identified for each brain regions, such as neuropeptide FF () for OBT, pro-melanin-concentrating hormone () for Hy, vesicular inhibitory amino acid transporter () for OT, excitatory amino acid transporter 1 () for Ce, peripherin () for Mo, and isotocin neurophysin () for RB. Additionally, the distribution of seven neurotransmitter-type neurons and five types of non-neuronal cells across different brain regions were analyzed by examining the expression of their marker genes. Notably, marker genes for glutamatergic and GABAergic neurons showed the highest expression levels across all brain regions. Similarly, the marker gene for radial astrocytes exhibited high expression compared to other markers, while those for microglia were the least expressed. Overall, our results provide a comprehensive overview of the structural and functional characteristics of distinct brain regions in the largemouth bass, which offers a valuable resource for understanding the role of central nervous system in regulating physiological processes in teleost.
Topics: Animals; Bass; Biomarkers; Brain; Neurons; Gene Expression Profiling; Transcriptome; Telencephalon
PubMed: 38745953
DOI: 10.3389/fendo.2024.1385575 -
Nutrients Apr 2024Sweat rate and electrolyte losses have a large inter-individual variability. A personalized approach to hydration can overcome this issue to meet an individual's needs.... (Randomized Controlled Trial)
Randomized Controlled Trial
Sweat rate and electrolyte losses have a large inter-individual variability. A personalized approach to hydration can overcome this issue to meet an individual's needs. This study aimed to investigate the effects of a personalized hydration strategy (PHS) on fluid balance and intermittent exercise performance. Twelve participants conducted 11 laboratory visits including a VO test and two 5-day trial arms under normothermic (NOR) or hyperthermic (HYP) environmental conditions. Each arm began with three days of familiarization exercise followed by two random exercise trials with either a PHS or a control (CON). Then, participants crossed over to the second arm for: NOR+PHS, NOR+CON, HYP+PHS, or HYP+CON. The PHS was prescribed according to the participants' fluid and sweat sodium losses. CON drank ad libitum of commercially-available electrolyte solution. Exercise trials consisted of two phases: (1) 45 min constant workload; (2) high-intensity intermittent exercise (HIIT) until exhaustion. Fluids were only provided in phase 1. PHS had a significantly greater fluid intake (HYP+PHS: 831.7 ± 166.4 g; NOR+PHS: 734.2 ± 144.9 g) compared to CON (HYP+CON: 369.8 ± 221.7 g; NOR+CON: 272.3 ± 143.0 g), regardless of environmental conditions ( < 0.001). HYP+CON produced the lowest sweat sodium concentration (56.2 ± 9.0 mmol/L) compared to other trials ( < 0.001). HYP+PHS had a slower elevated thirst perception and a longer HIIT (765 ± 452 s) compared to HYP+CON (548 ± 283 s, = 0.04). Thus, PHS reinforces fluid intake and successfully optimizes hydration status, regardless of environmental conditions. PHS may be or is an important factor in preventing negative physiological consequences during high-intensity exercise in the heat.
Topics: Humans; Water-Electrolyte Balance; Male; Hot Temperature; Exercise; Adult; Young Adult; Female; Sweating; Dehydration; Drinking; Sweat; Cross-Over Studies
PubMed: 38732589
DOI: 10.3390/nu16091341 -
Cellular and Molecular Life Sciences :... May 2024Trimeric G proteins transduce signals from a superfamily of receptors and each G protein controls a wide range of cellular and systemic functions. Their highly conserved...
Trimeric G proteins transduce signals from a superfamily of receptors and each G protein controls a wide range of cellular and systemic functions. Their highly conserved alpha subunits fall in five classes, four of which have been well investigated (Gs, Gi, G12, Gq). In contrast, the function of the fifth class, Gv is completely unknown, despite its broad occurrence and evolutionary ancient origin (older than metazoans). Here we show a dynamic presence of Gv mRNA in several organs during early development of zebrafish, including the hatching gland, the pronephros and several cartilage anlagen, employing in situ hybridisation. Next, we generated a Gv frameshift mutation in zebrafish and observed distinct phenotypes such as reduced oviposition, premature hatching and craniofacial abnormalities in bone and cartilage of larval zebrafish. These phenotypes could suggest a disturbance in ionic homeostasis as a common denominator. Indeed, we find reduced levels of calcium, magnesium and potassium in the larvae and changes in expression levels of the sodium potassium pump atp1a1a.5 and the sodium/calcium exchanger ncx1b in larvae and in the adult kidney, a major osmoregulatory organ. Additionally, expression of sodium chloride cotransporter slc12a3 and the anion exchanger slc26a4 is altered in complementary ways in adult kidney. It appears that Gv may modulate ionic homeostasis in zebrafish during development and in adults. Our results constitute the first insight into the function of the fifth class of G alpha proteins.
Topics: Animals; Zebrafish; Homeostasis; Zebrafish Proteins; GTP-Binding Protein alpha Subunits; Larva; Gene Expression Regulation, Developmental; Sodium-Potassium-Exchanging ATPase; Calcium; Kidney; Magnesium
PubMed: 38727814
DOI: 10.1007/s00018-024-05228-w