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Frontiers in Immunology 2024Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the...
Erythrocytes of the common carp are immune sentinels that sense pathogen molecular patterns, engulf particles and secrete pro-inflammatory cytokines against bacterial infection.
INTRODUCTION
Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers.
METHODS
We performed a series of experiments with RBCs exposed to , as well as laboratory infections using different concentrations of bacteria.
RESULTS
qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including and , in response to infection .
DISCUSSION
Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.
Topics: Animals; Carps; Erythrocytes; Cytokines; Aeromonas hydrophila; Gram-Negative Bacterial Infections; Fish Diseases; Phagocytosis; Pathogen-Associated Molecular Pattern Molecules; Immunity, Innate
PubMed: 38947329
DOI: 10.3389/fimmu.2024.1407237 -
BJA Open Jun 2024Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery...
Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.
BACKGROUND
Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment.
METHODS
Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses.
RESULTS
Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; <0.001) and Clavien-Dindo ≥3a (<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; =0.024, relative to ideal body weight; =0.001, body surface area; =0.009) and V/VCO at anaerobic threshold (=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival.
CONCLUSIONS
VO peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision.
CLINICAL TRIAL REGISTRATION
NCT03637647.
PubMed: 38947220
DOI: 10.1016/j.bjao.2024.100289 -
ACS Central Science Jun 2024Mitochondrial thermogenesis is a process in which heat is generated by mitochondrial respiration. In living organisms, the thermogenic mechanisms that maintain body...
Mitochondrial thermogenesis is a process in which heat is generated by mitochondrial respiration. In living organisms, the thermogenic mechanisms that maintain body temperature have been studied extensively in fat cells with little knowledge on how mitochondrial heat may act beyond energy expenditure. Here, we highlight that the exothermic oxygen reduction reaction (Δ ° = -286 kJ/mol) is the main source of the protonophore-induced mitochondrial thermogenesis, and this heat is conducted to other cellular organelles, including the nucleus. As a result, mitochondrial heat that reached the nucleus initiated the classical heat shock response, including the formation of nuclear stress granules and the localization of heat shock factor 1 (HSF1) to chromatin. Consequently, activated HSF1 increases the level of gene expression associated with the response to thermal stress in mammalian cells. Our results illustrate heat generated within the cells as a potential source of mitochondria-nucleus communication and expand our understanding of the biological functions of mitochondria in cell physiology.
PubMed: 38947196
DOI: 10.1021/acscentsci.3c01589 -
Research Square Jun 2024Little research has examined early life risk for symptoms of cognitive disengagement syndrome (CDS) despite a well-established literature regarding co-occurring outcomes...
BACKGROUND
Little research has examined early life risk for symptoms of cognitive disengagement syndrome (CDS) despite a well-established literature regarding co-occurring outcomes (e.g., attention-deficit/hyperactivity disorder). The current study estimated bivariate associations between early life risk factors and CDS in a large and representative sample of U.S. children.
METHODS
We conducted secondary analyses of baseline data from the Adolescent Brain Cognitive Development (ABCD) study (N = 8,096 children, 9-10 years old). Birthing parents reported early life risk factors on a developmental history questionnaire, including parental, prenatal, delivery and birth, and developmental milestone information. They also completed the Child Behavior Checklist, which includes a CDS subscale that was dichotomized to estimate the odds of elevated CDS symptoms (i.e., score > 70) in children related to risk indices.
RESULTS
We observed significantly elevated odds of CDS related to parental risk factors (i.e., unplanned pregnancy, pregnancy awareness after 6 weeks, teenage parenthood), birthing parent illnesses in pregnancy (i.e., severe nausea, proteinuria, pre-eclampsia/toxemia, severe anemia, urinary tract infection), pregnancy complications (i.e., bleeding), prenatal substance exposures (i.e., prescription medication, tobacco, illicit drugs), delivery and birth risk factors (i.e., child blue at delivery, child not breathing, jaundice, incubation after delivery), and late motor and speech milestones in children.
CONCLUSIONS
Several early-life risk factors were associated with elevated odds of CDS at ages 9-10 years; study design prevents the determination of causality. Further investigation is warranted regarding early life origins of CDS with priority given to risk indices that have upstream commonalities (i.e., that restrict fetal growth, nutrients, and oxygen).
PubMed: 38947040
DOI: 10.21203/rs.3.rs-4468007/v1 -
MedRxiv : the Preprint Server For... Jun 2024Obstructive sleep apnea (OSA) negatively impacts post-stroke recovery. This study's purpose: examine the prevalence of undiagnosed OSA and describe a simple tool to...
BACKGROUND
Obstructive sleep apnea (OSA) negatively impacts post-stroke recovery. This study's purpose: examine the prevalence of undiagnosed OSA and describe a simple tool to identify those at-risk for OSA in the early phase of stroke recovery.
METHODS
This was a cross-sectional descriptive study of people ∼15 days post-stroke. Adults with stroke diagnosis admitted to inpatient rehabilitation over a 3-year period were included if they were alert/arousable, able to consent/assent to participation, and excluded if they had a pre-existing OSA diagnosis, other neurologic health conditions, recent craniectomy, global aphasia, inability to ambulate 150 feet independently pre-stroke, pregnant, or inability to understand English. OSA was deemed present if oxygen desaturation index (ODI) of >=15 resulted from overnight oximetry measures. Prevalence of OSA was determined accordingly. Four participant characteristics comprised the "BASH" tool (body mass index >=35, age>=50, sex=male, hypertension=yes). A receiver operator characteristics (ROC) curve analysis was performed with BASH as test variable and OSA presence as state variable.
RESULTS
Participants (n=123) were 50.4% male, averaged 64.12 years old (sd 14.08), and self-identified race as 75.6% White, 20.3% Black/African American, 2.4%>1 race, and 1.6% other; 22% had OSA. ROC analysis indicated BASH score >=3 predicts presence of OSA (sensitivity=0.778, specificity=0.656, area under the curve =0.746, p<0.001).
CONCLUSIONS
Prevalence of undiagnosed OSA in the early stroke recovery phase is high. With detection of OSA post-stroke, it may be possible to offset untreated OSA's deleterious impact on post-stroke recovery of function. The BASH tool is an effective OSA screener for this application.
PubMed: 38947016
DOI: 10.1101/2024.06.16.24309011 -
Research Square Jun 2024Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide (O ) to molecular...
Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide (O ) to molecular oxygen (O ) and hydrogen peroxide (H O ) with proton-coupled electron transfers (PCETs). The reactivity of human MnSOD is determined by the state of a key catalytic residue, Tyr34, that becomes post-translationally inactivated by nitration in various diseases associated with mitochondrial dysfunction. We previously reported that Tyr34 has an unusual pK due to its proximity to the Mn metal and undergoes cyclic deprotonation and protonation events to promote the electron transfers of MnSOD. To shed light on the role of Tyr34 MnSOD catalysis, we performed neutron diffraction, X-ray spectroscopy, and quantum chemistry calculations of Tyr34Phe MnSOD in various enzymatic states. The data identifies the contributions of Tyr34 in MnSOD activity that support mitochondrial function and presents a thorough characterization of how a single tyrosine modulates PCET catalysis.
PubMed: 38946943
DOI: 10.21203/rs.3.rs-4494128/v1 -
International Journal of Nanomedicine 2024To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the...
PURPOSE
To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers.
MATERIALS AND METHODS
In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity.
RESULTS
The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors.
CONCLUSION
This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.
Topics: Animals; Photothermal Therapy; Reactive Oxygen Species; Nanoparticles; Cell Line, Tumor; Humans; Polylactic Acid-Polyglycolic Acid Copolymer; Mice; Indoles; Tumor Hypoxia; Radiation-Sensitizing Agents; Mice, Inbred BALB C; Mitochondria; Neoplasms; Nanomedicine
PubMed: 38946887
DOI: 10.2147/IJN.S450124 -
International Journal of Nanomedicine 2024Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating...
PURPOSE
Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection.
METHODS
First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF).
RESULTS
TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway.
CONCLUSION
TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.
Topics: Cerium; Animals; Mitochondria; Reactive Oxygen Species; Mice; Apoptosis; Hematopoiesis; Oxidative Stress; Cell Survival; Radiation-Protective Agents; Humans; Radiation Protection; Cell Line
PubMed: 38946882
DOI: 10.2147/IJN.S459607 -
Saudi Journal of Biological Sciences Aug 2024Plant phenolics have been known for various biological activities. This study aims to extract and examine the presence of phenolics in Bao mango (Mangifera indica L....
Plant phenolics have been known for various biological activities. This study aims to extract and examine the presence of phenolics in Bao mango (Mangifera indica L. var.) peel ethanolic extract (MPE). Further, antioxidant, anti-diabetic (α-amylase, and α-glucosidase inhibitory activity), and anti- Alzheimer's disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) inhibitory activity) efficacy of MPE were determined. The results indicated that mangiferin (8755.89 mg/ 100 g extract) was the major phenolic compound in MPE. An antioxidant mechanism revealed that MPE had a higher radical scavenging ability (4266.70 µmol TE/g extract) compared to reducing power (FRAP) or oxygen radical absorption capacity (ORAC). Further enzyme inhibitory assay against diabetic and AD involved enzymes showed that MPE had stronger inhibitory action against an enzyme involved in diabetes compared to their standard drug (Acarbose) (P < 0.05). While a lower IC value was observed against AD-involved enzymes compared to their standard drug (donepezil) (P < 0.05). The results show that Thai Bao mango peel byproduct can be a potential source of nutraceuticals to lower diabetes and improve cognitive health.
PubMed: 38946846
DOI: 10.1016/j.sjbs.2024.104033 -
Health Science Reports Jul 2024This article explored the possibility that the Mpox virus (MPXV) may initiate or stimulate the consequences of vascular inflammation. In 1970, it was discovered that...
BACKGROUND
This article explored the possibility that the Mpox virus (MPXV) may initiate or stimulate the consequences of vascular inflammation. In 1970, it was discovered that Macaca cynomolgus primates infected with MPXV also infected humans in the Democratic Republic of the Congo.
DISCUSSION
The study demonstrates that MPXV invades host cells via viral proteins and surface receptors, initiating the release of diverse inflammatory mediators such as IL-1, IL-6, TNF-α, CCL2, CXCL2, CXCL8, CXCL10, and so forth probably through endothelial dysfunction by reactive oxygen species production. In general, these mediators have been found to contribute to vascular inflammation and the formation of atherosclerotic plaque at a later stage, which may contribute to the onset of vascular inflammation.
CONCLUSION
The discussed association between vascular inflammation and Mpox has the potential to be an important finding in the field of vascular biology research.
PubMed: 38946778
DOI: 10.1002/hsr2.2223