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Frontiers in Immunology 2024P2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and...
INTRODUCTION
P2X receptors are a family of homo- and heterotrimeric cation channels gated by extracellular ATP. The P2X4 and P2X7 subunits show overlapping expression patterns and have been involved in similar physiological processes, such as pain and inflammation as well as various immune cell functions. While formation of P2X2/P2X3 heterotrimers produces a distinct pharmacological phenotype and has been well established, functional identification of a P2X4/P2X7 heteromer has been difficult and evidence for and against a physical association has been found. Most of this evidence stems, however, from model systems.
METHODS
Here, we used a P2X7-EGFP BAC transgenic mouse model as well as P2X4 and P2X7 knock-out mice to re-investigate a P2X4-P2X7 interaction in mouse lung by biochemical and immunohistochemical experiments as well as quantitative expression analysis.
RESULTS
No detectable amounts of P2X4 could be co-purified from mouse lung via P2X7-EGFP. In agreement with these findings, immuno-histochemical analysis using a P2X7-specific nanobody revealed only limited overlap in the cellular and subcellular localizations of P2X4 and P2X7 in both the native lung tissue and primary cells. Comparison of P2X4 and P2X7 transcript and protein levels in the respective gene-deficient and wild type mice showed no mutual interrelation between their expression levels in whole lungs. However, a significantly reduced expression was found in alveolar macrophages of mice.
DISCUSSION
In summary, our detailed analysis of the cellular and subcellular P2X4 and P2X7 localization and expression does not support a physiologically relevant direct association of P2X4 and P2X7 subunits or receptors .
Topics: Animals; Receptors, Purinergic P2X4; Receptors, Purinergic P2X7; Mice; Lung; Mice, Knockout; Mice, Transgenic; Mice, Inbred C57BL; Protein Binding
PubMed: 38953020
DOI: 10.3389/fimmu.2024.1425938 -
BioRxiv : the Preprint Server For... May 2024COVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest...
COVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest in peripheral tissue, not central like viral loadSpatial metabolomics allows detection of metabolites not altered overallSARS-CoV-2, the virus responsible for COVID-19, is a highly contagious virus that can lead to hospitalization and death. COVID-19 is characterized by its involvement in the lungs, particularly the lower lobes. To improve patient outcomes and treatment options, a better understanding of how SARS-CoV-2 impacts the body, particularly the lower respiratory system, is required. In this study, we sought to understand the spatial impact of COVID-19 on the lungs of mice infected with mouse-adapted SARS2-N501Y . Overall, infection caused a decrease in fatty acids, amino acids, and most eicosanoids. When analyzed by segment, viral loads were highest in central lung tissue, while metabolic disturbance was highest in peripheral tissue. Infected peripheral lung tissue was characterized by lower levels of fatty acids and amino acids when compared to central lung tissue. This study highlights the spatial impacts of SARS-CoV-2 and helps explain why peripheral lung tissue is most damaged by COVID-19.
PubMed: 38952797
DOI: 10.1101/2024.05.22.595414 -
The Canadian Veterinary Journal = La... Jul 2024A swine production system had 3 sections located a few kilometers apart. Sections A and C contained several thousand sows and nursery and finishing pigs. Section B,...
A swine production system had 3 sections located a few kilometers apart. Sections A and C contained several thousand sows and nursery and finishing pigs. Section B, located between the other 2 sections, was the smallest and had 6 finishing sites and 2 sow sites. The entire system was infected with porcine reproductive and respiratory syndrome virus, , and Section B was depopulated, cleaned, disinfected, and repopulated with negative gilts. Despite extreme measures, recontamination occurred for each pathogen, with aerosol considered the most plausible contamination source.
Topics: Animals; Swine; Aerosols; Swine Diseases; Mycoplasma hyopneumoniae; Actinobacillus pleuropneumoniae; Porcine respiratory and reproductive syndrome virus; Actinobacillus Infections; Pneumonia of Swine, Mycoplasmal; Female; Porcine Reproductive and Respiratory Syndrome; Animal Husbandry
PubMed: 38952762
DOI: No ID Found -
Oncoimmunology 2024Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive...
Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8 T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8 T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified , as a candidate gene expressed by tumor-specific T cells. In addition to expressing , tumor-specific T cells were present in a higher proportion of T cells co-expressing (PD-1)/(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients ( = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8 T cells in MPE, which are associated with patients' prognosis. (233 words).
Topics: Humans; Lung Neoplasms; CD8-Positive T-Lymphocytes; Pleural Effusion, Malignant; Single-Cell Analysis; Receptors, Antigen, T-Cell; T-Lymphocyte Subsets; Male; Female; Middle Aged; Aged; Antigens, Neoplasm
PubMed: 38952674
DOI: 10.1080/2162402X.2024.2371556 -
Cureus Jun 2024Background MXene is a newly discovered substance consisting of 2D transition metal carbides or nitrides, produced through the disintegration and etching of aluminum...
Background MXene is a newly discovered substance consisting of 2D transition metal carbides or nitrides, produced through the disintegration and etching of aluminum layers. It possesses numerous properties, including a high surface area, conductivity, strength, stiffness, negative zeta potential, and excellent volumetric capacitance. MXene is utilized in detecting anti-cancer medicine, while bismuth vanadate (BiVO) is synthesized to form an optimized material for anti-cancer activity applications. BiVO exhibits visible light absorption, strong chemical stability, and non-toxic properties. However, when loaded onto target stem cells, it can cause skin and respiratory irritation. Aim This study aimed to evaluate the facile fabrication of titanium carbide (TiC)-BiVO nanomaterials coupled with oxides for anti-cancer activity. Moreover, it aimed to create TiC-BiVO nanomaterials in combination with oxides using X-ray diffraction (XRD) and scanning electron microscopy (SEM) to assess their potential as efficient and targeted anti-cancer agents. Methods and materials To prepare the 2D TiC MXene, 2.5 g of titanium aluminum carbide (TiAlC) powder was dissolved in 60 mL of a 40% hydrofluoric acid (HF) solution in a polytetrafluoroethylene(PTFE) container. The etching process was made more efficient and completed in 24 hours by using a magnetic stirring system to keep the mixture stirred and heated continuously. The centrifugation was performed at 4000 rpm for five minutes. Subsequently, deionized water was used to wash the solution many times until its pH reached around 7. The appropriate TiC powder was made by vacuum drying the acquired sediment at 80°C for 24 hours. Monoclinic BiVO samples were synthesized via a hydrothermal method. Typically, 10 mmol of Bi(NO).5HO was dissolved in 100 mL of a 2 mol/L HNO solution and stirred uniformly. Subsequently, 10 mmol of ammonium metavanadate (NHVO) was added to the mixed solution. After being stirred for one hour, the mixture was transferred into a 100 mL sealed Teflon-lined stainless steel autoclave at 180°C for 16 hours. After cooling to room temperature, the sediment was washed three times with deionized water, ethanol, and acetone, respectively. Finally, the suspension was dried at 80°C, followed by calcination at 450°C for three hours to obtain BiVO. TiC-BiVO heterostructures were prepared by surface modification TiCusing BiVO suspensions by a simple, cost-effective approach. Results TiC nanosheets were observed with BiVO particles, and the high crystalline nature of the compound was confirmed after XRD analysis and energy-dispersive spectroscopy (EDS) analysis. The compound was found to be pure without any impurities and exhibited anti-cancer activity. Conclusion The XRD, field emission scanning electron microscopy(FESEM), and EDS investigations provide an in-depth analysis of the structural, morphological, and compositional characteristics of TiC-BiVO sheets. The XRD analysis proves the successful combination of different materials and the presence of crystalline phases. The FESEM imaging technique exposes the shape and arrangement of particles in sheets, while the EDS analysis verifies the elemental composition and uniform distribution. These investigations show that TiC-BiVO composites have been successfully synthesized, indicating their potential for use in anti-cancer applications.
PubMed: 38952587
DOI: 10.7759/cureus.61492 -
Frontiers in Neurology 2024Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female...
24-h continuous non-invasive multiparameter home monitoring of vitals in patients with Rett syndrome by an innovative wearable technology: evidence of an overlooked chronic fatigue status.
BACKGROUND
Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 () gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients.
METHODS
A total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7-35.5 years) with typical RTT and pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L'Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients' contributions to the surrounding water vapor partial pressure [P (pt)] and carbon dioxide [P (pt)] were indirectly estimated.
RESULTS
Of the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03-82%)] and HR/LF [median: 3.75 (interquartile range 3.19-5.05)] were elevated, independent from the wake-sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients ( ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing.
CONCLUSION
Our findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression.
PubMed: 38952469
DOI: 10.3389/fneur.2024.1388506 -
Veterinary Medicine and Science Jul 2024Acute flaccid paralysis (AFP) is a complex clinical syndrome with various aetiologies. If untreated, AFP may lead to death due to failure of respiratory muscles. Tick...
BACKGROUND
Acute flaccid paralysis (AFP) is a complex clinical syndrome with various aetiologies. If untreated, AFP may lead to death due to failure of respiratory muscles. Tick paralysis, which is a noninfectious neurologic syndrome of AFP, occurs following tick attachment, engorgement, and injection of tick saliva toxins. There is no specific diagnostic test for tick paralysis, and mortality increases as definitive diagnosis is delayed. Although metabolomic investigation of tick saliva was conducted, there is a lack of research on metabolomic evaluation of hosts affected by tick paralysis.
OBJECTIVES
Thus, the aim of this study is to investigate metabolomic changes in serum samples of dogs with tick paralysis due to Rhipicephalus sanguineus using NMR-based metabolomics and to identify potential diagnostic/prognostic markers.
MATERIALS AND METHODS
Forty dogs infested with R. sanguineus, with clinical findings compatible with AFP and with a confirmed tick paralysis diagnosis ex juvantibus, constituted the Paralysis Group. Ten healthy dogs, which were admitted either for vaccination and/or check-up purposes, constituted the Control Group. After the confirmation tick paralysis, medical history, vaccination and nutritional status, body surface area and estimated tick numbers of all the dogs were noted. Physical examination included body temperature, heart and respiratory rate, capillary refill time evaluation and Modified Glasgow Coma Scale calculation. Serum samples were extracted from venous blood samples of all the dogs and were prepared for NMR analysis, and NMR-based metabolomics identification and quantification were performed.
RESULTS
NMR-based serum metabolomics of the present study revealed distinct up/down-regulated expressions, presenting a promising avenue. Moreover, it was observed that energy metabolism and especially liver functions were impaired in dogs with tick paralysis, and not only the respiratory system but also the kidneys were affected.
CONCLUSION
It was concluded that the present approach may help to better understand the pathological mechanisms developing in cases of AFP due to tick paralysis.
Topics: Animals; Dogs; Tick Paralysis; Dog Diseases; Magnetic Resonance Spectroscopy; Metabolomics; Female; Male; Rhipicephalus sanguineus; Metabolome; Paralysis
PubMed: 38952268
DOI: 10.1002/vms3.1528 -
JMIR Public Health and Surveillance Jun 2024Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI),... (Observational Study)
Observational Study
BACKGROUND
Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI), targeted and rapid interventions can be facilitated that prevent COVID-19 outbreaks without primary reliance on testing.
OBJECTIVE
This study aims to assess the temporal relationship between confirmed SARS-CoV-2 infections and self-reported and health care provider-reported CLI in university and county settings, respectively.
METHODS
We collected aggregated COVID-19 testing and symptom reporting surveillance data from Cornell University (2020-2021) and Tompkins County Health Department (2020-2022). We used negative binomial and linear regression models to correlate confirmed COVID-19 case counts and positive test rates with CLI rate time series, lagged COVID-19 cases or rates, and day of the week as independent variables. Optimal lag periods were identified using Granger causality and likelihood ratio tests.
RESULTS
In modeling undergraduate student cases, the CLI rate (P=.003) and rate of exposure to CLI (P<.001) were significantly correlated with the COVID-19 test positivity rate with no lag in the linear models. At the county level, the health care provider-reported CLI rate was significantly correlated with SARS-CoV-2 test positivity with a 3-day lag in both the linear (P<.001) and negative binomial model (P=.005).
CONCLUSIONS
The real-time correlation between syndromic surveillance and COVID-19 cases on a university campus suggests symptom reporting is a viable alternative or supplement to COVID-19 surveillance testing. At the county level, syndromic surveillance is also a leading indicator of COVID-19 cases, enabling quick action to reduce transmission. Further research should investigate COVID-19 risk using syndromic surveillance in other settings, such as low-resource settings like low- and middle-income countries.
Topics: Humans; COVID-19; Retrospective Studies; Universities; Sentinel Surveillance
PubMed: 38952000
DOI: 10.2196/54551 -
Journal of Cardiothoracic Surgery Jul 2024In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Comparative analysis of the analgesic effects of intercostal nerve block, ultrasound-guided paravertebral nerve block, and epidural block following single-port thoracoscopic lung surgery.
OBJECTIVE
In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery.
METHOD
A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects.
RESULTS
In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P < 0.05). However, there was a higher incidence of side effects observed in the EB group (P < 0.05).
CONCLUSION
The analgesic effect of PVB and EB following single-port thoracoscopic lung surgery is better than that of ICNB. PVB causes fewer side effects and complications and is safer and more effective.
Topics: Humans; Nerve Block; Female; Male; Middle Aged; Intercostal Nerves; Ultrasonography, Interventional; Pain, Postoperative; Thoracic Surgery, Video-Assisted; Aged; Pain Measurement; Adult; Thoracoscopy; Lung
PubMed: 38951892
DOI: 10.1186/s13019-024-02877-7 -
American Journal of Primatology Jul 2024Respiration is an invaluable signal that facilitates the real-time observation of physiological dynamics. In recent years, the advancement of noncontact measurement...
Respiration is an invaluable signal that facilitates the real-time observation of physiological dynamics. In recent years, the advancement of noncontact measurement technology has gained momentum in capturing physiological activities in natural settings. This technology is anticipated to be found not only in humans but also in nonhuman primates. Currently, the predominant noncontact approach for nonhuman animals involves measuring vital signs through subtle variations in skin color. However, this approach is limited when addressing areas of the body covered with hair or when working in outdoor settings under fluctuating sunlight. To overcome this issue, we focused on noncontact respiratory measurements using millimeter-wave radar. Millimeter-wave radar systems, which employ millimeter waves that can penetrate animal fur and estimate respiration-derived periodic body motion, exhibit minimal susceptibility to sunlight interference. Thus, this method shows potential for conducting noncontact vital measurements in natural and outdoor settings. In this study, we validated a millimeter-wave radar methodology for capturing respiration in outdoor-housed rhesus macaques (Macaca mulatta). The radar was positioned beyond the captive enclosure and maintained at a distance >5 m from the target. Millimeter waves were transmitted to the target, and the reflected waves were used to estimate skin surface displacement associated with respiration. The results revealed periodic skin surface displacement, and the estimated respiratory rates weres within the reported range of respiratory rates for rhesus macaques. These results suggest the potential applicability of millimeter-wave radar for noncontact respiration monitoring in outdoor-living macaques without anesthesia or immobilization. The continued advancement of noncontact vital measurement technology will contribute to understanding primate mental and physical dynamics during their daily life.
PubMed: 38951734
DOI: 10.1002/ajp.23661