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Military Medical Research Jun 2024Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with...
BACKGROUND
Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed.
METHODS
db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein-protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays.
RESULTS
In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P < 0.01). Hepatic PANX1 overexpression ameliorated the dysregulated glucolipid metabolism in obese mice. Mice with hepatic PANX1 knockdown or global PANX1 knockout exhibited disturbed glucolipid metabolism. Restoration of hepatic PANX1 rescued the metabolic disorders of PANX1-deficient mice (P < 0.05). Mechanistically, ATP release is mediated by the PANX1-activated protein kinase B-forkhead box protein O1 (Akt-FOXO1) pathway to inhibit gluconeogenesis via P2Y receptors in hepatocytes. PANX1-mediated ATP release also activated calmodulin (CaM) (P < 0.01), which interacted with c-Jun N-terminal kinase (JNK) to inhibit its activity, thereby deactivating the transcription factor activator protein-1 (AP1) and repressing fatty acid synthase (FAS) expression and lipid synthesis (P < 0.05). FAM3A stimulated the expression of PANX1 via heat shock factor 1 (HSF1) in hepatocytes (P < 0.05). Notably, FAM3A overexpression failed to promote ATP release, inhibit the expression of gluconeogenic and lipogenic genes, and suppress gluconeogenesis and lipid deposition in PANX1-deficient hepatocytes and livers.
CONCLUSIONS
PANX1-mediated release of ATP plays a crucial role in maintaining hepatic glucolipid homeostasis, and it confers FAM3A's suppressive effects on hepatic gluconeogenesis and lipogenesis.
Topics: Animals; Connexins; Mice; Gluconeogenesis; Nerve Tissue Proteins; Adenosine Triphosphate; Lipogenesis; Liver; Mice, Knockout; Male; Humans; Diet, High-Fat; Cytokines
PubMed: 38937853
DOI: 10.1186/s40779-024-00543-6 -
Nature Communications Jun 2024Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid...
Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.
Topics: Animals; Porosity; Chitosan; Hemostatics; Swine; Hemostasis; Permeability; Hemorrhage; Male
PubMed: 38937462
DOI: 10.1038/s41467-024-49578-2 -
International Journal of... Jun 2024Lower cardiovascular reactivity is a proposed marker of motivational dysregulation and is related to a range of adverse behavioural and health outcomes. Social...
Lower cardiovascular reactivity is a proposed marker of motivational dysregulation and is related to a range of adverse behavioural and health outcomes. Social participation is a form of motivated behaviour and represents the frequency in which an individual engages in social activities. Low social participation has recently been linked to lower cardiovascular responses to acute psychological stress. With recent work emphasizing the importance of assessing adaptation of the cardiovascular response to recurrent stress, the aim of the current study is to build on previous work by examining the relationship between social participation and cardiovascular stress response adaptation. This study utilised data from the Pittsburgh Cold Study 3 (PCS 3). Two hundred and thirteen participants (M = 30.13; SD = 10.85) completed a social participation measure and had their systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) monitored across two separate standardized stress testing sessions. The testing sessions consisted of a 20-minute baseline and a 15-minute stress task. Results indicated that higher levels of social participation were associated with greater blood pressure habituation to recurrent stress, extending previous work identifying that social participation was associated with higher cardiovascular responses to stress. The present study identifies that those reporting greater levels of social participation may show enhanced stress tolerance when exposed to recurrent stress.
PubMed: 38936701
DOI: 10.1016/j.ijpsycho.2024.112389 -
Computer Methods and Programs in... Jun 2024Synchronous acquisition of haemodynamic signals is crucial for their multimodal analysis, such as dynamic cerebral autoregulation (DCA) analysis of arterial blood...
BACKGROUND
Synchronous acquisition of haemodynamic signals is crucial for their multimodal analysis, such as dynamic cerebral autoregulation (DCA) analysis of arterial blood pressure (ABP) and transcranial Doppler (TCD)-derived cerebral blood velocity (CBv). Several technical problems can, however, lead to (varying) time-shifts between the different signals. These can be difficult to recognise and can strongly influence the multimodal analysis results.
METHODS
We have developed a multistep, cross-correlation-based time-shift detection and synchronisation algorithm for multimodal pulsatile haemodynamic signals. We have developed the algorithm using ABP and CBv measurements from a dataset that contained combinations of several time-shifts. We validated the algorithm on an external dataset with time-shifts. We additionally quantitatively validated the algorithm's performance on a dataset with artificially added time-shifts, consisting of sample clock differences ranging from -0.2 to 0.2 s/min and sudden time-shifts between -4 and 4 s. The influence of superimposed noise and variation in waveform morphology on the time-shift estimation was quantified, and their influence on DCA-indices was determined.
RESULTS
The instantaneous median absolute error (MedAE) between the artificially added time-shifts and the estimated time-shifts was 12 ms (median, IQR 12-12, range 11-14 ms) for drifts between -0.1 and 0.1 s/min and sudden time-shifts between -4 and 4 s. For drifts above 0.1 s/min, MedAE was higher (median 753, IQR 19 - 766, range 13 - 772 ms). When a certainty threshold was included (peak cross-correlation > 0.9), MedAE for all drifts-shift combinations decreased to 12 ms, with smaller variability (IQR 12 - 13, range 8 - 22 ms, p < 0.001). The time-shift estimation is robust to noise, as the MedAE was similar for superimposed white noise with variance equal to the signal variance. After time-shift correction, DCA-indices were similar to the original, non-time-shifted signals. Phase shift differed by 0.17° (median, IQR 0.13-0.2°, range 0.0038-1.1°) and 0.54° (median, IQR 0.23-1.7°, range 0.0088-5.6°) for the very low frequency and low frequency ranges, respectively.
DISCUSSION
This algorithm allows visually interpretable detection and accurate correction of time-shifts between pulsatile haemodynamic signals (ABP and CBv).
PubMed: 38936154
DOI: 10.1016/j.cmpb.2024.108298 -
PloS One 2024High blood pressure, also known as hypertension (HTN), is a complicated disorder that is controlled by a complex network of physiological processes. Untreated...
BACKGROUND
High blood pressure, also known as hypertension (HTN), is a complicated disorder that is controlled by a complex network of physiological processes. Untreated hypertension is associated with increased death incidence, rise the need for understanding the genetic basis affecting hypertension susceptibility and development. The current study sought to identify the genetic association between twelve single nucleotide polymorphisms (SNPs) within seven candidate genes (NOS3, NOS1AP, REN, PLA2G4A, TCF7L, ADRB1, and PTPRD).
METHODS
The current study included 200 Jordanian individuals diagnosed with hypertension, compared to 224 healthy controls. Whole blood samples were drawn from each individual for DNA isolation and genotyping. The SNPStats tool was used to assess haplotype, genotype, and allele frequencies by the mean of chi-square (χ2).
RESULTS
Except for rs10739150 of PTPRD (P = 0.0003), the genotypic and allelic distribution of the SNP was identical between patients and controls. The prevalence of the G/G genotype in healthy controls (45.5%) was lower than in hypertension patients (64.3%), suggesting that it might be a risk factor for the disease. PTPRD TTC genetic haplotypes were strongly linked with hypertension (P = 0.003, OR = 4.03).
CONCLUSION
This study provides a comprehensive understanding of the involvement of rs10739150 within the PTPRD gene in hypertension. This new knowledge could potentially transform the way we approach hypertension diagnosis, providing an accurate diagnostic tool for classifying individuals who are at a higher risk of developing this condition.
Topics: Humans; Polymorphism, Single Nucleotide; Hypertension; Female; Male; Middle Aged; Genetic Predisposition to Disease; Adult; Gene Frequency; Haplotypes; Case-Control Studies; Receptor-Like Protein Tyrosine Phosphatases, Class 2; Genotype; Jordan; Alleles
PubMed: 38935682
DOI: 10.1371/journal.pone.0304950 -
PloS One 2024Diabetes is a chronic disease associated with the potential for blindness, kidney failure, heart attacks, strokes, and lower limb amputations. The global prevalence of...
BACKGROUND
Diabetes is a chronic disease associated with the potential for blindness, kidney failure, heart attacks, strokes, and lower limb amputations. The global prevalence of diabetes is rising, particularly in the sub-Saharan African (SSA) region, where accessing treatment and antidiabetic drugs is complex, leading to challenges in managing the condition. Intentional and structured therapeutic education has demonstrated its ability to enhance health outcomes in diabetes patients. Given the numerous healthcare deficiencies in sub-Saharan Africa, the authors have reevaluated the role of therapeutic patient education (TPE) in this context.
METHODS
This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We queried four databases between March 14 and June 30, 2023 and conducted Cochrane's Risk of Bias analysis on the included studies. Subsequently, a qualitative synthesis of the results was performed.
RESULTS
The final analysis included thirteen studies. Seven of these, which assessed glycemic control, reported statistically significant results. Additionally, other clinical parameters such as body mass index (BMI), blood pressure, and lipid levels also exhibited some significant improvements. Knowledge substantially increased following the intervention, while attitude, self-care practices, and medication adherence showed no significant improvements. Nurse-led and peer-led intervention programs produced positive outcomes, whereas technology-based intervention methods did not yield favorable results.
CONCLUSION
TPE programs in sub-Saharan Africa have a significant impact on both clinical and non-clinical outcomes in diabetes patients. However, the sustainability of these outcomes remains uncertain. Further research is needed to assess the long-term effects of TPE on diabetes patients.
Topics: Humans; Africa South of the Sahara; Patient Education as Topic; Diabetes Mellitus; Medication Adherence; Self Care; Health Knowledge, Attitudes, Practice
PubMed: 38935594
DOI: 10.1371/journal.pone.0299526 -
Journal of the American Heart... Jul 2024Postpartum hypertension is a risk factor for severe maternal morbidity; however, barriers exist for diagnosis and treatment. Remote blood pressure (BP) monitoring...
BACKGROUND
Postpartum hypertension is a risk factor for severe maternal morbidity; however, barriers exist for diagnosis and treatment. Remote blood pressure (BP) monitoring programs are an effective tool for monitoring BP and may mitigate maternal health disparities. We aimed to describe and evaluate engagement in a remote BP monitoring program on BP ascertainment during the first 6-weeks postpartum among a diverse patient population.
METHODS AND RESULTS
A postpartum remote BP monitoring program, using cell-enabled technology and delivered in multiple languages, was implemented at a large safety-net hospital. Eligible patients are those with hypertensive disorders before or during pregnancy. We describe characteristics of patients enrolled from January 2021 to May 2022 and examine program engagement by patient characteristics. Linear regression models were used to calculate mean differences and 95% CIs between characteristics and engagement metrics. We describe the prevalence of patients with BP ≥140/or >90 mm Hg. Among 1033 patients, BP measures were taken an average of 15.2 days during the 6-weeks, with the last measurement around 1 month (mean: 30.9 days), and little variability across race or ethnicity. Younger maternal age (≤25 years) was associated with less frequent measures (mean difference, -4.3 days [95% CI: -6.1 to -2.4]), and grandmultiparity (≥4 births) was associated with shorter engagement (mean difference, -3.5 days [95% CI, -6.1 to -1.0]). Prevalence of patients with BP ≥140/or >90 mm Hg was 62.3%, with differences by race or ethnicity (Black: 72.9%; Hispanic: 52.4%; White: 56.0%).
CONCLUSIONS
A cell-enabled postpartum remote BP monitoring program was successful in uniformly monitoring BP and capturing hypertension among a diverse, safety-net hospital population.
Topics: Humans; Female; Adult; Safety-net Providers; Pregnancy; Blood Pressure; Postpartum Period; Blood Pressure Determination; Hypertension, Pregnancy-Induced; Telemedicine; Hypertension; Young Adult
PubMed: 38934890
DOI: 10.1161/JAHA.123.034031 -
Journal of the American Heart... Jul 2024Women are known to be disadvantaged compared with men in the early links of the Chain of Survival, receiving fewer bystander interventions. We aimed to describe...
BACKGROUND
Women are known to be disadvantaged compared with men in the early links of the Chain of Survival, receiving fewer bystander interventions. We aimed to describe sex-based disparities in emergency medical service resuscitation quality and processes of care for out-of-hospital cardiac arrest.
METHODS AND RESULTS
We conducted a retrospective analysis of patients who were nontraumatic with out-of-hospital cardiac arrest aged ≥16 years where resuscitation was attempted between March 2019 and June 2023. We investigated 18 routinely captured performance metrics and performed adjusted logistic and quantile regression analyses to assess sex-based differences in these metrics. During the study period, 10 161 patients with out-of-hospital cardiac arrest met the eligibility criteria, of whom 3216 (32%) were women. There were no clinically relevant sex-based differences observed in regard to external cardiac compressions; however, women were 34% less likely to achieve a systolic blood pressure >100 mm Hg on arrival at the hospital (adjusted odds ratio [AOR], 0.66 [95% CI, 0.47-0.92]). Furthermore, women had a longer time to 12-lead ECG acquisition after return of spontaneous circulation (median adjusted difference, 1.00 minute [95% CI, 0.38-1.62]) and 33% reduced odds of being transported to a 24-hour percutaneous coronary intervention-capable facility (AOR, 0.67 [95% CI, 0.49-0.91]). Resuscitation was also terminated sooner for women compared with men (median adjusted difference, -4.82 minutes [95% CI, -6.77 to -2.87]).
CONCLUSIONS
Although external cardiac compression quality did not vary by sex, significant sex-based disparities were seen in emergency medical services processes of care following out-of-hospital cardiac arrest. Further investigation is required to elucidate the underlying causes of these differences and examine their influence on patient outcomes.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Female; Male; Cardiopulmonary Resuscitation; Retrospective Studies; Middle Aged; Aged; Healthcare Disparities; Sex Factors; Emergency Medical Services; Adult
PubMed: 38934889
DOI: 10.1161/JAHA.123.033974 -
Journal of the American Heart... Jul 2024The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones...
BACKGROUND
The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones including daidzein, glycitein, genistein, equol (a gut microbial metabolite of daidzein), and equol-predicting microbial species with cardiometabolic risk markers.
METHODS AND RESULTS
In a 1-year study of 305 Chinese community-dwelling adults aged ≥18 years, urinary isoflavones, fecal microbiota, blood pressure, blood glucose and lipids, and anthropometric data were measured twice, 1 year apart. Brachial-ankle pulse wave velocity was also measured after 1 year. A linear mixed-effects model was used to analyze repeated measurements. Logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% CI for the associations for arterial stiffness. Each 1 μg/g creatinine increase in urinary equol concentrations was associated with 1.47%, 0.96%, and 3.32% decrease in triglycerides, plasma atherogenic index, and metabolic syndrome score, respectively (all <0.05), and 0.61% increase in high-density lipoprotein cholesterol (=0.025). Urinary equol was also associated with lower risk of arterial stiffness (aOR, 0.28 [95% CI, 0.09-0.90]; =0.036). We identified 21 bacterial genera whose relative abundance was positively associated with urinary equol (false discovery rate-corrected <0.05) and constructed a microbial species score to reflect the overall equol-predicting capacity. This score (per 1-point increase) was inversely associated with triglycerides (percentage difference=-1.48%), plasma atherogenic index (percentage difference=-0.85%), and the risk of arterial stiffness (aOR, 0.27 [95% CI, 0.08-0.88]; all <0.05).
CONCLUSIONS
Our findings suggest that urinary equol and equol-predicting microbial species may improve cardiometabolic risk parameters in Chinese adults.
Topics: Humans; Equol; Male; Female; Middle Aged; Cardiometabolic Risk Factors; Biomarkers; China; Adult; Gastrointestinal Microbiome; Vascular Stiffness; Cardiovascular Diseases; Risk Assessment; Isoflavones; Feces; East Asian People
PubMed: 38934874
DOI: 10.1161/JAHA.123.034126 -
Journal of the American Heart... Jul 2024Experimental preeclampsia (ePE) has been shown to have worsened outcome from stroke. We investigated the effect of low-dose aspirin, known to prevent preeclampsia, on...
BACKGROUND
Experimental preeclampsia (ePE) has been shown to have worsened outcome from stroke. We investigated the effect of low-dose aspirin, known to prevent preeclampsia, on stroke hemodynamics and outcome, and the association between the vasoconstrictor and vasodilator cyclooxygenase products thromboxane A and prostacyclin.
METHODS AND RESULTS
Middle cerebral artery occlusion was performed for 3 hours with 1 hour of reperfusion in normal pregnant rats on day 20 of gestation and compared with ePE treated with vehicle or low-dose aspirin (1.5 mg/kg per day). Multisite laser Doppler was used to measure changes in cerebral blood flow to the core middle cerebral artery and collateral vascular territories. After 30 minutes occlusion, phenylephrine was infused to increase blood pressure and assess cerebral blood flow autoregulation. Infarct and edema were measured using 2,3,5-triphenyltetrazolium chloride staining. Plasma levels of thromboxane A, prostacyclin, and inflammatory markers in plasma and cyclooxygenase levels in cerebral arteries were measured. ePE had increased infarction compared with normal pregnant rats (<0.05) that was reduced by aspirin (<0.001). ePE also had intact cerebral blood flow autoregulation and reduced collateral perfusion during induced hypertension that was also prevented by aspirin. Aspirin increased prostacyclin in ePE (<0.05) without reducing thromboxane B, metabolite of thromboxane A, or 8-isoprostane-prostaglandin-2α, a marker of lipid peroxidation. There were no differences in cyclooxygenase levels in cerebral arteries between groups.
CONCLUSIONS
Low-dose aspirin in ePE reduced infarction that was associated with increased vasodilator prostacyclin and improved collateral perfusion during induced hypertension. The beneficial effect of aspirin on the brain and cerebral circulation is likely multifactorial and worth further study.
Topics: Animals; Female; Pregnancy; Aspirin; Cerebrovascular Circulation; Pre-Eclampsia; Homeostasis; Rats, Sprague-Dawley; Disease Models, Animal; Collateral Circulation; Thromboxane A2; Infarction, Middle Cerebral Artery; Blood Flow Velocity; Rats; Epoprostenol; Laser-Doppler Flowmetry
PubMed: 38934871
DOI: 10.1161/JAHA.124.035990