Carbamylated lipoproteins in diabetes

Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.

Astrocytes dynamically regulate the blood-brain barrier in the healthy brain

The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.

Nanotechnologies meeting natural sources:Engineered lipoproteins for precise brain disease theranostics

Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain diseases.However,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical translation.To address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions.In this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are highlighted.Furthermore,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized.Specifically,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed.Finally,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.

In vivo label-free measurement of blood flow velocity symmetry based on dual line scanning third-harmonic generation microscopy excited at the 1700 nm window

Measurement of bloodflow velocity is key to understanding physiology and pathology in vivo.While most measurements are performed at the middle of the blood vessel,little research has been done on characterizing the instantaneous bloodflow velocity distribution.This is mainly due to the lack of measurement technology with high spatial and temporal resolution.Here,we tackle this problem with our recently developed dual-wavelength line-scan third-harmonic generation(THG)imaging technology.Simultaneous acquisition of dual-wavelength THG line-scanning signals enables measurement of bloodflow velocities at two radially symmetric positions in both venules and arterioles in mouse brain in vivo.Our results clearly show that the instantaneous bloodflow velocity is not symmetric under general conditions.

Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

Effect of sodium nitroprusside on the microrheological properties of red blood cells in different media

Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.

Clinical nursing value of predictive nursing in reducing complications of pregnant women undergoing short-term massive blood transfusion during cesarean section

BACKGROUND Cesarean hemorrhage is one of the serious complications,and short-term massive blood transfusion can easily cause postoperative infection and physical stress response.However,predictive nursing intervention has important clinical significance for it.AIM To explore the effect of predictive nursing intervention on the stress response and complications of women undergoing short-term mass blood transfusion during cesarean section(CS).METHODS A clinical medical record of 100 pregnant women undergoing rapid mass blood transfusion during sections from June 2019 to June 2021.According to the different nursing methods,patients divided into control group(n=50)and observation group(n=50).Among them,the control group implemented routine nursing,and the observation group implemented predictive nursing intervention based on the control group.Moreover,compared the differences in stress res-ponse,complications,and pain scores before and after the nursing of pregnant women undergoing rapid mass blood transfusion during CS.RESULTS The anxiety and depression scores of pregnant women in the two groups were significantly improved after nursing,and the psychological stress response of the observation group was significantly lower than that of the control group(P<0.05).The heart rate and mean arterial pressure(MAP)of the observation group during delivery were lower than those of the control group,and the MAP at the end of delivery was lower than that of the control group(P<0.05).Moreover,different pain scores improved significantly in both groups,with the observation group considerably less than the control group(P<0.05).After nursing,complications such as skin rash,urinary retention,chills,diarrhea,and anaphylactic shock in the observation group were 18%,which significantly higher than in the control group(4%)(P<0.05).CONCLUSION Predictive nursing intervention can effectively relieve the pain,reduce the incidence of complications,improve mood and stress response,and serve as a reference value for the nursing of women undergoing rapid mass transfusion during CS.

Preoperative blood markers and intra-abdominal infection after colorectal cancer resection

BACKGROUND Colorectal cancer(CRC)has one of the highest morbidity and mortality rates among digestive tract tumors.Intra-abdominal infection(IAI)is a common postoperative complication that affects the clinical outcomes of patients with CRC and hinders their rehabilitation process.However,the factors influencing abdominal infection after CRC surgery remain unclear;further,prediction models are rarely used to analyze preoperative laboratory indicators and postoperative complications.AIM To explore the predictive value of preoperative blood markers for IAI after radical resection of CRC.METHODS The data of 80 patients who underwent radical resection of CRC in the Anorectal Surgery Department of Suzhou Hospital affiliated with Anhui Medical University were analyzed.These patients were categorized into IAI(n=15)and non-IAI groups(n=65)based on whether IAI occurred.Influencing factors were compared;general data and laboratory indices of both groups were identified.The relationship between the indicators was assessed.Further,a nomogram prediction model was developed and evaluated;its utility and clinical applic-ability were assessed.RESULTS The risk factors for IAI after radical resection of CRC were neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),and carcinoembryonic antigen(CEA)levels.NLR was correlated with PLR and SII(r=0.604,0.925,and 0.305,respectively),while PLR was correlated with SII(r=0.787).The nomogram prediction model demonstrated an area under the curve of 0.968[95%confidence interval(CI):0.948-0.988]in the training set(n=60)and 0.926(95%CI:0.906-0.980)in the validation set(n=20).The average absolute errors of the calibration curves for the training and validation sets were 0.032 and 0.048,respectively,indicating a good model fit.The decision curve analysis curves demonstrated high net income above the 5%threshold,indicating the clinical practicality of the model.CONCLUSION The nomogram model constructed using NLR,PLR,SII,and CEA levels had good accuracy and reliability in predicting IAI after radical resection of CRC,potentially aiding clinical treatment decision-making.

Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation

Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.

The effectiveness of physical activity interventions on blood pressure in children and adolescents:A systematic review and network meta-analysis

Background:High blood pressure(BP)is a major contributor to mortality and cardiovascular diseases.Despite the known benefits of exercise for reducing BP,it is crucial to identify the most effective physical activity(PA)intervention.This systematic review and network meta-analysis(NMA)aimed to evaluate the available evidence on the effectiveness of various PA interventions for reducing BP and to determine their hierarchy based on their impact on BP.Methods:A search of PubMed,SPORTDiscus,PsycINFO,Web of Science,CINAHL,Cochrane,and Eric databases was conducted up to December 2022 for this systematic review and NMA.Randomized controlled trials and quasi-experimental studies targeting healthy children and adolescents aged 6-12 years old were included in this study.Only studies that compared controlled and intervention groups using PA or exercise as the major influence were included.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines.Three independent investigators performed the literature screening,data extraction,and risk of bias assessment.We used Bayesian arm-based NMA to synthesize the data.The primary outcomes were systolic BP and diastolic BP.We calculated the mean differences(MDs)in systolic BP and diastolic BP before and after treatment.Mean treatment differences were estimated using NMA and random-effect models.Results:We synthesized 27 studies involving 15,220 children and adolescents.PA combined with nutrition and behavior change was the most effective intervention for reducing both systolic BP and diastolic BP(MD=-8.64,95%credible interval(95%CI):-11.44 to-5.84;MD=-6.75,95%CI:-10.44 to-3.11),followed by interventions with multiple components(MD=-1.39,95%CI:-1.94 to-0.84;MD=-2.54,95%CI:-4.89 to-0.29).Conclusion:Our findings suggest that PA interventions incorporating nutrition and behavior change,followed by interventions with multiple components,are most effective for reducing both systolic BP and diastolic BP in children and adolescents.

Selective Removal of Low-Density Lipoproteins from Blood by Induced Precipitation with AAS in Vitro(Ⅰ)

1 INTRODUCTION It’s evident that high level of cholesterol in blood is associated with the formation and devel-opment of familial hypercholestrolemia(FH)and atherosclerosis(AS).In general,choles-terol in blood is mainly combined with low-density lipoproteins(LDL),very low-densitylipoproteins(VLDL)and high density lipoproteins(HDL).About 60%-80% cholesterolexists in LDL and VLDL.LDL and VLDL have been recognized as the principal

Association of Thyroid Nodules with Various Elements in Urine and Blood Serum: A Case-Control Study

Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.

Sex Disparities in the Association of Blood Pressure Parameters and Arterial Sclerosis Risk

Cardiovascular disease(CVD)is the leading cause of death worldwide[1].Arterial sclerosis(AS)and hypertension are the main risk factors and pathological bases of CVD.Higher pulse wave velocity(PWV)measurements could reflect early progression of atherosclerosis.Based on the structure-function properties of the vascular wall and hemodynamics,strong evidence suggests that any increase in blood pressure levels can mechanically impair the ability of the endothelium to maintain vascular homeostasis[2].High levels of blood pressure parameters,such as systolic blood pressure(SBP),diastolic blood pressure(DBP),pulse pressure(PP),and mean arterial pressure(MAP)have been identified as essential risk biomarkers for atherosclerosis.

Impact of Regular Blood Donation on Body Iron Stores at Saudi Blood Donors

Introduction: One of the most frequent observations in long-term blood donation is chronic iron deficiency, which can develop into anaemia. The majority of blood screening methods employed by blood banks do not incorporate iron-status markers, which may result in potential subclinical iron deficiency. The aim of this study was to evaluate the effects of repeated blood donation on the levels of iron in the body and to guide blood donors in preventing the depletion of iron stores. Methods: Regular blood donors were categorised into distinct groups according to the number of donations they gave, and then the correlation between these groups and their bodies’ iron levels was examined. Different parameters were employed to identify iron deficiency and iron depletion in blood donors: serum ferritin, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total iron-binding capacity (TIBC), and serum iron. Results: The study included 300 individuals who regularly and willingly donated blood. There were no iron insufficiency cases among those donating blood for the first time (Group I). However, 15.5% of individuals who had donated once before (Group II) had ferritin levels of 15 - 30 μg/dl (ng/ml), indicating reduced iron stores. The rate increased to 18% (37 out of 206 individuals) among regular blood donors (Groups III, IV, and V). Iron deficiency (depletion) prevalence among regular blood donors in Groups III, IV, and V was 5.9% (12 out of 206) and 50.4% (100 out of 206). Donors who had donated blood most frequently had the lowest levels of haematological markers MCH, MCHC, and TIBC. Provide the p-values representing the differences between the means of MCV, MCH, iron, TIBC, and ferritin levels when comparing donor groups with the control group (Group I) based on the frequency of donations. Indicate statistically significant differences where the p-value is less than 0.0125. This significance level is adjusted based on the Bonferroni method, considering multiple independent tests. The result shows that the Iron parameter for the comparison between Group I and Group III and Group I and Group IV suggests a statistically significant difference in iron levels between these donor groups. Conclusion: The findings of this study show that a higher times of donations lads to a higher occurrence of depleted iron stores and subsequent erythropoiesis with iron deficiency by one donor from every three healthy donors. The iron and ferritin concentrations were within the normal range in group one (Control group) and reduced in the other four groups (G-2 to G-5). However, the level of haemoglobin remained within an acceptable range for blood donation. This outcome suggests that it may be necessary to reassess the criteria for accepting blood donors. The average serum ferritin levels were examined in all five groups (G-1 to G-5), both for males and females, and significant variations were seen among the groups under study. This study found that 35% of the individuals who regularly donate blood have iron-deficient anaemia (sideropenia). This suggests that it would be beneficial to test for serum ferritin at an earlier stage, ideally after three donations.

Identification of Key Blood Biomarkers Linking Di(2-ethylhexyl)Phthalate and Autoimmune Diseases in Adolescents Mice

Di(2-ethylhexyl)phthalate(DEHP)is a widely used plasticizer known for its reproductive developmental and immune system toxicity,mainly through esophagal,dermal,and respiratory exposure^([1-3]).Maternal exposure to DEHP during pregnancy can lead to adverse birth outcomes in offspring,including impacts on the thyroid system of adolescent offspring^([2-4]).

Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity

Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related diseases.The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.Methods Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the study.The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses.Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),P<0.001].Multivariate stepwise logistic regression analysis demonstrated that the MHR[odds ratio(OR):1.033,95%confidence interval(CI):1.015-1.051;P<0.001]was an independent predictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;P<0.001].Additionally,MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.

Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.

Low-density lipoprotein receptor-related protein 2(LRP2)is required for lipid export in the midgut of the migratory locust,Locusta migratoria

Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.

Heterogeneous patterning of blood-brain barrier and adaptive myelination as renewing key in gray and white matter

Background:Development and homeostasis of the brain are enabled through the precise control of the cell microenvironment by the blood-brain barrier(BBB),which interfaces between the brain parenchyma and the lumen of blood microvessels,and by the blood-cerebrospinal fluid barrier,which separates the cerebrospinal fluid from the blood vessels of the choroid plexus(Villabona-Rueda et al.,2019).Here,the focus will be on the BBB,the impairment of which is considered the earliest common denominator in neurovascular diseases.

A natural nano-platform:Advances in drug delivery system with recombinant high-density lipoprotein

Developing natural nano-platforms with high biocompatibility and natural targeting ability represents great significance for drug delivery.High-density lipoprotein(HDL),a natural lipid-protein complex,plays important roles in physiological activities,particularly in reverse cholesterol transport(RCT)and be closely associated with atherosclerotic cardiovascular diseases.Recent studies have demonstrated that HDLs have the potential to serve as ideal drug carriers.Recombinant HDLs(r HDLs)have been used to encapsulate substances such as small interfering RNA(siRNA),drugs,and contrast agents,fully utilizing the biocompatibility and targeting ability of r HDL in the body and providing new strategies for drug delivery and disease treatment.In this review,we discussed in detail the basic principles of HDL as a drug delivery system,the mechanisms of targeted drug delivery,and several methods for preparing HDL nanoparticles.Afterward,we comprehensively reviewed the applications of HDL as a drug carrier in cardiovascular diseases,cancer treatment(such as glioblastoma,breast cancer,hepatocellular carcinoma and urologic cancers)and some other fields.Finally,we reviewed the therapeutic effects and safety of HDL nanoparticles in clinical studies.Through a review and summary of these research advances,we aim to fully understand the potential of HDL as a drug carrier in clinical applications,providing valuable references and guidance for future research and expedites the translational application of HDL as drug carriers.