Unraveling Changes of Brachial Artery Residual Stress and Its Relationship to Cardiovascular Disease Risk Factors.

Background: Arterial pressure volume index (API) offers a non-invasive measurement of brachial artery residual stress. This study investigated API distribution characteristics and correlations with cardiovascular disease risk (CVD) factors in a large Chinese population sample. Methods: This cross-sectional study surveyed a total of 7620 participants. We analyzed the relationships between API and factors influencing CVD, using regression-based stepwise backward selection and restrictive cubic spline models to express relationships as standardized beta values. Results: Multiple linear regression analysis identified many independent factors influencing API including age, sex, body mass index (BMI), pulse pressure (PP), heart rate (HR), hemoglobin, uric acid (UA), estimated glomerular filtration rate (eGFR), triglyceride (TC), and a history of hypertension. Notably, API values increased at 33 and escalated with advancing age. Increases in API were associated with rises in PP and UA increases, particularly when PP reached 60 mmHg and the UA reached 525 units. Conversely, API was found to decrease with elevated HR and eGFR. Furthermore, there was a significant inverted U-shaped relationship between API and BMI. Conclusions: This study was the first to describe API distribution characteristics in a large sample of the Chinese population, providing references for evaluating API changes in the assessment of residual stress variations in diverse diseases. Notably, API displayed a U-shaped relationship with age and was closely related to traditional CVD risk factors, underscoring its potential as a non-invasive tool for risk assessment in vascular health. Clinical Trial Registration: This research was registered with the China Clinical Trial Registration Center (Registration Number: ChiCTR2000035937).

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Natural products as pharmacological modulators of mitochondrial dysfunctions for the treatment of diabetes and its complications: An update since 2010.

Diabetes, characterized as a well-known chronic metabolic syndrome, with its associated complications pose a substantial and escalating health and healthcare challenge on a global scale. Current strategies addressing diabetes are mainly symptomatic and there are fewer available curative pharmaceuticals for diabetic complications. Thus, there is an urgent need to identify novel pharmacological targets and agents. The impaired mitochondria have been associated with the etiology of diabetes and its complications, and the intervention of mitochondrial dysfunction represents an attractive breakthrough point for the treatments of diabetes and its complications. Natural products (NPs), with multicenter characteristics, multi-pharmacological activities and lower toxicity, have been caught attentions as the modulators of mitochondrial functions in the therapeutical filed of diabetes and its complications. This review mainly summarizes the recent progresses on the potential of 39 NPs and 2 plant-extracted mixtures to improve mitochondrial dysfunction against diabetes and its complications. It is expected that this work may be useful to accelerate the development of innovative drugs originated from NPs and improve upcoming therapeutics in diabetes and its complications.

Structural modification of oat protein by thermosonication combined with high pressure for O/W emulsion and model salad dressing production.

Oat protein is becoming an important ingredient in beverages and formulated foods owing to its high nutritive value and bland flavor; yet, its functionality remains largely unexplored. This study sought to enhance the surface activity of oat protein isolate (OPI) through high-intensity ultrasound (HIU; at 20 or 60 °C) combined with high pressure homogenization (HP; 30 MPa) treatments. Sonication disturbed the protein conformation and significantly improved surface hydrophobicity (19.7%) and ζ-potential (15.7%), which were further augmented by subsequent HP (P < 0.05). Confocal microscopy revealed a uniform oil droplet distribution in emulsions prepared with HIU+HP combination treated OPI, and the oil droplet size decreased up to 35.6% when compared to that of non-treated OPI emulsion (d = 1718 nm). Emulsifying activity was greater for HIU+HP than for HIU, and the viscosity followed a similar trend. Moreover, while emulsions prepared with HIU or HP treated OPI were more stable than control, the 60 °C HIU+HP combination treatment yielded the maximum stability. In corroboration, a model salad dressing prepared from HIU+HP treated OPI displayed a homogenous oil droplet distribution and an improved viscosity. Therefore, thermosonication combined with high pressure homogenization may be suitable for salad dressings and other oil-imbedded food products.

Selective Separation of Americium(III), Curium(III), and Lanthanide(III) by Aqueous and Organic Competitive Extraction.

Adding hydrophilic ligands into aqueous solutions for the selective binding of actinides(III) is acknowledged as an advanced strategy in Ln(III)/An(III) separation. In view of the recycling and radioactive waste disposal of the minor actinide, there remains an urgent need to design and develop the appropriate ligand for selective separation of An(III) from Ln(III). Herein, four novel hydrophilic ligands with hard-soft hybrid donors, derived from the pyridine and phenanthroline skeletons, were designed and synthesized as masking agents for selective complexation of An(III) in the aqueous phase. The known N,N,N',N'-tetraoctyl diglycolamide (TODGA) was used as lipophilic extractant in the organic phase for extraction of Ln(III), and a new strategy for the competitive extraction of An(III) and Ln(III) was developed based on TODGA and the above hydrophilic ligands. The optimal hydrophilic ligand of N,N'-bis(2-hydroxyethyl)-2,9-dicarboxamide-1,10-phenanthroline (2OH-DAPhen) displayed exceptional selectivity toward Am(III) over Ln(III), with the concentrations of HNO3 ranging from 0.05 to 3.0 M. The maximum separation factors were up to 1365 for Eu/Am, 417.66 for Eu/Cm, and 42.38 for La/Am. The coordination mode and bonding property of 2OH-DAPhen with Ln(III) were investigated by 1H NMR titration, UV-vis spectrophotometric titration, luminescence titration, FT-IR, ESI-HRMS analysis, and DFT calculations. The results revealed that the predominant species formed in the aqueous phase was a 1:1 ligand/metal complex. DFT calculations also confirmed that the affinity of 2OH-DAPhen for Am(III) was better than that for Eu(III). The present work using a competitive extraction strategy developed a feasible alternative method for the selective separation of trivalent actinides from lanthanides.

Adeno-associated virus-9 reverses delayed gastric emptying of solids in diabetic mice.

BACKGROUND: Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis. Upregulation of HO1 expression via interleukin-10 (IL-10) in the gastric muscularis propria is associated with reversal of delayed GE in diabetic NOD mice. IL-10 activates the M2 cytoprotective phenotype of macrophages and induces expression of HO1 protein. Here, we assess delivery of HO1 by recombinant adeno-associated viruses (AAVs) in diabetic mice with delayed GE. METHODS: C57BL6 diabetic delayed GE mice were injected with 1 × 1012 vg scAAV9-cre, scAAV9-GFP, or scAAV9-HO1 particles. Changes to GE were assessed weekly utilizing our [13 C]-octanoic acid breath test. Stomach tissue was collected to assess the effect of scAAV9 treatment on Kit, NOS1, and HO1 expression. KEY RESULTS: Delayed GE returned to normal within 2 weeks of treatment in 7/12 mice receiving scAAV9-cre and in 4/5 mice that received the scAAV9-GFP, whereas mice that received scAAV9-HO1 did not respond in the same manner and had GE that took significantly longer to return to normal (6/7 mice at 4-6 weeks). Kit, NOS1, and HO1 protein expression in scAAV9-GFP-treated mice with normal GE were not significantly different compared with diabetic mice with delayed GE. CONCLUSIONS AND INFERENCES: Injection of scAAV9 into diabetic C57BL6 mice produced a biological response that resulted in acceleration of GE independently of the cargo delivered by the AAV9 vector. Further research is needed to determine whether use of AAV mediated gene transduction in the gastric muscularis propria is beneficial and warranted.

Increased arterial pressure volume index and cardiovascular risk score in China.

BACKGROUND AND OBJECTIVE: The new non-invasive arterial stiffness indices, arterial pressure volume index (API) is explored as a novel marker of residual stress in the wall of the peripheral muscular arteries at zero-stress state in clinical settings. The present study aimed to study the association of API with cardiovascular disease (CVD) risk in China (China-PAR). METHODS: According to China-PAR score, participants were divided into three groups: low risk (< 5%), medium risk (5-9.9%), and high risk (≥ 10.0%). API ≥ 31 was defined as high API, and the incidences of high API were compared. Logistic regression models were used to analyze the risk factors of high API and high risk China-PAR categories. The association between China-PAR and API was analyzed by restrictive cubic spline. RESULTS: The study included 4311 participants. After adjustments for confounding factors, high API was independent factor associated with high risk China-PAR categories, and the probability of high API was 1.366 times higher than that in normal API subjects. While, the independent factors associated with high API were BMI, blood pressure and heart rate. Furthermore, API had a significant U-shaped association with China-PAR. CVD risk was lowest with API of 19 units, the fastest increase at 26 units and the flattest starting point at 59 units. CONCLUSION: API, an indicator of arterial stiffness and residual stress, had a U-shaped association with China-PAR score and might play an important role in predicting CVD risk in Chinese natural populations.

Relationship of Arterial Stiffness and Central Hemodynamics With Cardiovascular Risk In Hypertension.

BACKGROUND: Hypertension is becoming a serious public health problem and noninvasive estimation of central hemodynamics and artery stiffness have been identified as important predictors of cardiovascular disease. METHODS: The study included 4,311 participants, both sex and aged between 20 and 79 years. Arterial velocity pulse index, arterial pressure-volume index (AVI, API, and the index of artery stiffness), central systolic blood pressure, central artery pulse pressure (CSBP, CAPP, and estimated via oscillometric blood pressure monitor), and 10-year risk score of cardiovascular disease in China (China-PAR) and Framingham cardiovascular risk score (FCVRS) were assessed at baseline. Regression model was performed to identify factors associated with high cardiovascular disease risk stratification. The relationships between CSBP, CAPP and China-PAR, and FCVRS were analyzed by restrictive cubic spline functions. RESULTS: The uncontrolled hypertension group showed the highest values of AVI, API, CSBP, and CAPP. In the regression analysis, CAPP and hypertension subtypes were identified as significant predictors of high cardiovascular risk stratification, and CAPP was strongly correlated with API in this cohort. Finally, CSBP and CAPP showed significant J-shaped relationships with China-PAR and FCVRS. CONCLUSIONS: Subjects with uncontrolled hypertension present with elevated values of CAPP, CSBP, API, AVI, China-PAR, and FCVRS scores. CAPP was independently associated with high cardiovascular risk stratification, and there was a significant J-shaped relationship with China-PAR and FCVRS that may identify people with higher cardiovascular risk.

Arterial Stiffness, Body Mass Index and Cardiovascular Disease Risk in Chinese Females at Various Ages.

Background: This study investigated the correlation in parameters of arterial stiffness and cardiovascular disease (CVD) risk on age and body mass index (BMI) in Chinese females. Methods: This cross-sectional study enrolled 2220 females. Arterial stiffness was assessed by the measurement of arterial velocity pulse index (AVI) and arterial pressure volume index (API). Individual 10-year cardiovascular risk was calculated for each patient using the Framingham cardiovascular risk score (FCVRS). Results: API and AVI had a significant J-shaped relationship with age. Beginning at the age of 30 years, the API started to increase, while after 49 years, the increase in API was even steeper. AVI increased from the age of 32 years, and increased more rapidly after 56 years. The linear association between API and BMI following adjustment for age was significant ( ß = 0.324, 95% CI 0.247-0.400, p < 0.001). In the total study cohort, FCVRS scores increased by 0.16 scores for every 1 kg/ m 2 increase in BMI and by 0.11 scores for each 1 value increase in API in the age adjusted model. Conclusions: API and BMI correlate with 10-year cardiovascular risk at various ages in females. Regardless of age, overweight females have a higher risk of increased API. Therefore API can be used for the early detection of CVD so that preventive therapy can be instituted in these high risk patients. Clinical Trial Registration: Registered on the official website of the China Clinical Trial Registration Center (20/08/2020, ChiCTR2000035937).