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International Wound Journal Jul 2024The uncertainty concerning the physiological effects of compression bandaging on the peripheral blood flow is a challenge for healthcare professionals. The main...
The uncertainty concerning the physiological effects of compression bandaging on the peripheral blood flow is a challenge for healthcare professionals. The main objective was to determine the haemodynamic impact on the distal posterior tibial artery after the application of a high-compression leg multicomponent bandaging system using 4D flow magnetic resonance imaging. Leg dominance disparities of the posterior tibial artery before and after the application of the compressive bandage were also analysed. Twenty-eight healthy female volunteers were recruited (mean: 25.71, standard deviation: 4.74 years old) through a non-probability convenience sampling. The 4D flow magnetic resonance imaging of the distal tibial posterior artery was performed in all participants, first under standard resting conditions and after the application of a compression bandage in the leg. When the strong compressive bandage was applied, the area of the assessed artery decreased by 14.2%, whilst the average speed increased by 19.6% and the flow rate increased by 184.8%. There were differences between the haemodynamic parameters of both legs according to dominance, being statistically significantly lower in the dominant leg. The application of strong compressive bandaging significantly increases the arterial flow and mean velocity in the distal segment of the posterior tibial artery, in healthy volunteers by 4D flow magnetic resonance imaging. In this study, leg dominance influenced some of the haemodynamic parameters. According to the results, leg compression bandages cannot be contraindicated in vascular ulcers with arterial compromise.
Topics: Humans; Female; Tibial Arteries; Adult; Compression Bandages; Magnetic Resonance Imaging; Hemodynamics; Young Adult; Healthy Volunteers; Leg
PubMed: 38937919
DOI: 10.1111/iwj.14901 -
Journal of Experimental & Clinical... Jun 2024This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and...
BACKGROUND
This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and micrometastasis in locally advanced gastric cancer (LAGC).
METHODS
We used genome-wide transcriptome profiling and rigorous bioinformatics to identify a six-gene expression biomarker panel. This panel was validated across multiple clinical cohorts using both tissue and liquid biopsy samples to predict peritoneal recurrence and micrometastasis in patients with LAGC.
RESULTS
Through genome-wide expression profiling, we identified six mRNAs and developed a risk prediction model using 196 samples from a surgical specimen training cohort. This model, incorporating a 6-mRNA panel with clinical features, demonstrated high predictive accuracy for peritoneal recurrence in gastric cancer patients, with an AUC of 0.966 (95% CI: 0.944-0.988). Transitioning from invasive surgical or endoscopic biopsy to noninvasive liquid biopsy, the model retained its predictive efficacy (AUC = 0.963; 95% CI: 0.926-1.000). Additionally, the 6-mRNA panel effectively differentiated patients with or without peritoneal metastasis in 95 peripheral blood specimens (AUC = 0.970; 95% CI: 0.936-1.000) and identified peritoneal micrometastases with a high efficiency (AUC = 0.941; 95% CI: 0.874-1.000).
CONCLUSIONS
Our study provides a novel gene expression biomarker panel that significantly enhances early detection of peritoneal recurrence and micrometastasis in patients with LAGC. The RSA model's predictive capability offers a promising tool for tailored treatment strategies, underscoring the importance of integrating molecular biomarkers with clinical parameters in precision oncology.
Topics: Humans; Stomach Neoplasms; Liquid Biopsy; Female; Neoplasm Micrometastasis; Male; Peritoneal Neoplasms; Neoplasm Recurrence, Local; Biomarkers, Tumor; Gene Expression Profiling; Middle Aged; Transcriptome; Aged
PubMed: 38937855
DOI: 10.1186/s13046-024-03098-5 -
ENeuro Jun 2024Ghrelin is a stomach-derived hormone that increases feeding and is elevated in response to chronic psychosocial stressors. The effects of ghrelin on feeding are mediated...
Ghrelin is a stomach-derived hormone that increases feeding and is elevated in response to chronic psychosocial stressors. The effects of ghrelin on feeding are mediated by the binding of ghrelin to the growth hormone secretagogue receptor (GHSR), a receptor located in hypothalamic and extra-hypothalamic regions important for regulating food intake and metabolic rate. The ability of ghrelin to enter the brain, however, seems to be restricted to circumventricular organs like the median eminence and the brain stem area postrema (AP), whereas ghrelin does not readily enter other GHSR expressing regions like the ventral tegmental area (VTA). Interestingly, social stressors result in increased blood brain barrier permeability, and this could therefore facilitate the entry of ghrelin into the brain. To investigate this, we exposed mice to social defeat stress for 21 days, then peripherally injected a Cy5-labelled biologically active ghrelin analogue. Results demonstrate that chronically stressed mice exhibit higher Cy5-ghrelin fluorescence in several hypothalamic regions in addition to the ARC, including the hippocampus and midbrain. Furthermore, Cy5-ghrelin injections resulted in increased FOS expression in regions associated with the reward system in the chronically stressed mice. Further histologic analyses identified a reduction in branching of hypothalamic astrocytes in the ARC-median eminence junction, suggesting increased blood-brain barrier permeability. These data support the hypothesis that during metabolically challenging conditions like chronic stress, ghrelin may be more able to cross the blood brain barrier and diffuse throughout the brain to target GHSR expressing brain regions away from circumventricular organs. Ghrelin is secreted in response to negative energy balance states including stress and is associated with changes in food intake and energy balance. The receptors for ghrelin are found throughout the brain but ghrelin seems to only reach circumventricular regions where the blood brain barrier is more porous. In this paper we demonstrate that chronic social defeat stress increases brain permeability to ghrelin to allow for entry and activation of target sites in the mesolimbic dopaminergic system that are not accessible to ghrelin under non-stress conditions. Overall, these results provide for an explanation as to how ghrelin can access the mesolimbic dopaminergic system in a state dependent manner.
PubMed: 38937108
DOI: 10.1523/ENEURO.0093-24.2024 -
Redox Biology Jun 2024The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance...
INTRODUCTION
The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance and inflammation at rest and in response to acute exercise, and exercise performance in female athletes.
METHODS
Twelve female endurance athletes (age: 26.8 ± 3.4 yrs, maximum oxygen uptake (V˙O): 55.2 ± 5.1 mL × min × kg) were included in a randomized, single-blinded crossover study. They were allocated to begin with either 14 days of optimal energy availability diet (OEA, 52 ± 2 kcal × kg fat free mass (FFM) × day) or LEA diet (22 ± 2 kcal × kg FFM × day), followed by 3 days of refueling (OEA) with maintained training volume. Peripheral blood mononuclear cells (PBMCs) were isolated, and plasma obtained at rest before and after each dietary period. The PBMCs were used for analysis of mitochondrial respiration and HO emission and specific proteins. Exercise performance was assessed on cycle by a 20-min time trial and time to exhaustion at an intensity corresponding to ∼110 % V˙O).
RESULTS
LEA was associated with a 94 % (P = 0.003) increase in PBMC NADPH oxidase 2 protein content, and a 22 % (P = 0.013) increase in systemic cortisol. LEA also caused an alteration of several inflammatory related proteins (P < 0.05). Acute exercise augmented HO emission in PBMCs (P < 0.001) following both OEA and LEA, but to a greater extent following LEA. LEA also reduced the mobilization of white blood cells with acute exercise. After LEA, performance was reduced in both exercise tests (P < 0.001), and the reduced time trial performance remained after the 3 days of refueling (P < 0.001).
CONCLUSION
14 days of LEA in female athletes increased cortisol levels and had a pronounced effect on the immune system, including increased capacity for ROS production, altered plasma inflammatory proteome and lowered exercise induced mobilization of leukocytes. Furthermore, LEA resulted in a sustained impairment in exercise performance.
PubMed: 38936255
DOI: 10.1016/j.redox.2024.103250 -
Poultry Science Jun 2024White Leghorn chickens from a common founder population have been divergently selected for high (HAS) or low (LAS) antibody responses to sheep red blood cells (SRBC) for...
Selection for high and low antibody responses to sheep red blood cells influences cytokine and chemokine expression in chicken peripheral blood leukocytes and splenic tissue.
White Leghorn chickens from a common founder population have been divergently selected for high (HAS) or low (LAS) antibody responses to sheep red blood cells (SRBC) for 49 generations resulting in 2 diverse lines for this trait. Much has been studied in these two lines; however, the impact of these selection pressures on cytokine and chemokine expression is not fully understood. The purpose of this study is to determine if selection for antibody response to SRBC impacts cytokine and chemokine expression in peripheral blood leukocytes (PBL) and spleen from HAS and LAS chickens. Total RNA was isolated from PBL and spleen after which mRNA expression of cytokines (IL4, IL6, IL10, TGF-β4) and chemokines (CXCL8, CCL4) were determined by quantitative real-time RT-PCR (qRT-PCR). The data were analyzed using Student's t test comparing HAS and LAS (P < 0.05) and are reported as corrected 40-C. PBL and spleen samples were analyzed separately. With respect to PBL, expression of IL6 was higher (P < 0.05) in PBL isolated from LAS chickens compared to those from the HAS line whereas there were no differences (P > 0.05) in IL4, IL10, CXCL8, CCL4, or TGF-β4. The cytokine and chemokine mRNA expression profiles were different in the spleen between the two lines. IL4 and CXCL8 expression were higher (P < 0.05) in spleen samples from HAS chickens than LAS. The expression of IL6, IL10, CCL4, or TGF-β4 in the spleens did not differ (P > 0.05) between the lines. The data indicate that selection for specific antibody responses to SRBC impacts the cytokine and chemokine expression profile in PBL and spleens but in different ways in HAS and LAS. These studies provide insight into the influence that selection pressures for antibody responses have on different immune response components, specifically cytokines and chemokines typically involved in the innate response.
PubMed: 38936074
DOI: 10.1016/j.psj.2024.103972 -
Neural Regeneration Research Jun 2024Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered...
Chitosan alleviates symptoms of Parkinson's disease by reducing acetate levels, which decreases inflammation and promotes repair of the intestinal barrier and blood-brain barrier.
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically short-chain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood-brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood-brain barriers, thereby alleviating symptoms of Parkinson's disease.
PubMed: 38934394
DOI: 10.4103/NRR.NRR-D-23-01511 -
Kidney & Blood Pressure Research Jun 2024The aim of the presented prospective observational study was to evaluate the effect of fistula flow on peripheral wave morphology and pulse wave velocity by means of the...
UNLABELLED
The aim of the presented prospective observational study was to evaluate the effect of fistula flow on peripheral wave morphology and pulse wave velocity by means of the oscillometric Vicorder®-device with the purpose of fistula surveillance.
METHODS
Digitized and normalized curves of 53 haemodialysis patients at the fistula and non-fistula arm were analyzed. Slope parameters and the areas under the curve of characteristic sections of pulse waves as well as the power spectrum of the pulse waves and their first and second derivatives were computed. Furthermore, the amplitude of volumetric change (AMP) was assessed. Duplex-sonography served as a reference method.
RESULTS
In the comprehensive set of novel pulse wave parameters significant inter-arm differences were demonstrated and a significant delay of the systolic maximum at the fistula arm in comparison to the non-fistula arm (204 ± 3.4 versus 162 ± 5.3 ms, p<0.001) was proven. Unexpectedly, pulse wave velocity apparently did not differ between both arms (7.85 versus 8.05 m/sec at the fistula/non-fistula side, p=0.942). The inter-arm differences of the slope parameters were more pronounced in forearm than in upper arm fistulas. Finally, we showed that the inter-arm difference of AMP correlated with volume-flow (r= 0.326 with p=0.017).
CONCLUSION
Pulse waves as assessed by oscillometric pulse wave analysis have distinct features at fistula and non-fistula arms. This is due to enhanced arteriovenous flow, i.e. in both the brachial artery and the fistula vein. The analysis of those alterations has the potential to assess fistula function.
PubMed: 38934146
DOI: 10.1159/000539885 -
Cancer Research Communications Jun 2024To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin Lymphoma (HL) and immune checkpoint modulation induced by...
PURPOSE
To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin Lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA-4 and PD1.
PATIENTS AND METHODS
Phase 1/2, multicenter, open-label, trial NCT01896999 enrolled patients with refractory or relapsed HL (R/R HL) after one or more lines of therapy, with adequate performance status and organ function. Using peripheral blood, we assessed soluble proteins, cell composition, T cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial.
RESULTS
NCT01896999 reported high (>75%) overall objective response rates with brentuximab-vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed durable increase in soluble PD-1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV+N and BV+I+N) compared with BV+I (p<0.05). Non-responders and patients with short progression free-survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (p<0.05).
CONCLUSIONS
The results suggest a circulating tumor-immune-derived signature of BV±I+N treatment resistance that may be useful for patient stratification in combination checkpoint therapy.
PubMed: 38934093
DOI: 10.1158/2767-9764.CRC-24-0252 -
Molecular Therapy. Methods & Clinical... Jun 2024Mucolipidosis IV (MLIV) is a rare, autosomal recessive, lysosomal disease characterized by intellectual disability, motor deficits, and progressive vision loss. Using...
Mucolipidosis IV (MLIV) is a rare, autosomal recessive, lysosomal disease characterized by intellectual disability, motor deficits, and progressive vision loss. Using adeno-associated vector 9 (AAV9) and AAV-PHP.B as delivery vectors, we previously demonstrated the feasibility of modifying disease course in a mouse model of MLIV by the human gene transfer. Here, using a primate-enabling capsid AAV.CPP.16 (CPP16), we constructed a new, clinic-oriented gene expression vector and demonstrated its efficacy in the preclinical model of MLIV. Systemic administration of CPP16-MCOLN1 in adult symptomatic mice at a dose of 1e12 vg per mouse resulted in expression in the brain and peripheral tissues, alleviated brain pathology, rescued neuromotor function, and completely prevented paralysis. Notable expression of transcripts was also detected in the retina of the mouse, which had exhibited significant degeneration at the time of the treatment. However, no increase in retinal thickness was observed after gene therapy treatment. Our results suggest a new AAV-based systemic gene replacement therapy for the treatment of MLIV that could be translated into clinical studies.
PubMed: 38934011
DOI: 10.1016/j.omtm.2024.101269 -
Heliyon Jun 2024The incidence of Crohn's disease (CD) and rheumatoid arthritis (RA) co-morbidity, as well as the number of individuals affected, is on the rise due to their shared...
OBJECTIVE
The incidence of Crohn's disease (CD) and rheumatoid arthritis (RA) co-morbidity, as well as the number of individuals affected, is on the rise due to their shared molecular and cellular factors. This study aimed to identify potential therapeutic targets and medicines for comorbid CD and RA.
METHODS
We integrated single-cell RNA sequencing, Mendelian randomization, and colocalization analysis results from public databases to analyse immune cell subgroups in CD and RA patients and identify candidate therapeutic targets. We further screened potential medicines for the identified candidate targets using the Comparative Toxicogenomics Database (CTD) and molecular docking and molecular dynamics simulations.
RESULTS
The proportion of CD8 effector memory T cells (Tem) was consistently elevated in the peripheral blood mononuclear cells (PBMCs) of both CD and RA patients. MYBL1 had a causal effect on the onset of both CD (OR = 1.23; 95 % CI, 1.05-1.45; P = 0.046) and RA (OR = 1.45; 95 % CI, 1.14-1.85; P = 0.04). Four potential therapeutic molecules were retrieved from the CTD database, among which tretinoin (docking score: -6.3 kcal/mol) showed the best potential.
CONCLUSION
Our comprehensive analysis suggests that CD8 Tem cells are a key cell group in comorbid RA and CD and that MYBL1 has a causal effect. Tretinoin was identified as a potential targeted therapeutic drug, which is of great clinical research value.
PubMed: 38933947
DOI: 10.1016/j.heliyon.2024.e32406