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Journal of Clinical Medicine Apr 2024: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways...
Effect of an Intensive Lifestyle Intervention on Circulating Biomarkers of Atrial Fibrillation-Related Pathways among Adults with Metabolic Syndrome: Results from a Randomized Trial.
: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. : We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. : At baseline, participants' mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (-14%, 95% confidence interval (CI) -26%, 0%) or smaller increases in 3-NT (-16%, 95% CI -25%, -5%) and NT-proBNP (-12%, 95% CI -23%, 1%). The intervention had minimal impact on hsTnT (-3%, 95% CI -7%, 2%) or PICP concentrations (-2%, 95% CI -9%, 6%). The effect of the intervention on hsCRP was primarily mediated by weight loss (89% at year 5). : Over five years, a dietary and lifestyle intervention for weight-loss favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, pointing to specific mechanisms in pathways linking lifestyles and AF.
PubMed: 38610897
DOI: 10.3390/jcm13072132 -
Journal of Back and Musculoskeletal... Mar 2024The effect of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion (LIF) for lumbar degenerative diseases is not well known.
BACKGROUND
The effect of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion (LIF) for lumbar degenerative diseases is not well known.
OBJECTIVE
This study aimed to evaluate the effect of perioperative anti-osteoporosis treatment in the patients with osteoporosis and LIF.
METHODS
From January to December 2022, patients were divided into three groups according to the inclusive criteria: the normal group (Group A), the osteopenia group (Group B) and the osteoporosis group (Group C). Quantitative computed tomography (QCT), height of the intervertebral space (HIS), segmental sagittal angle (SSA), visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were compared between the groups at the follow-up time. The serum Ca2 + , osteocalcin (OC), propeptide of type I procollagen (PINP) C-terminal cross-linking telopeptide of type I collagen (β-CTX) and 25-OH vitamin D (25-OH VD) levels were compared between the groups at the time of follow-up. Interbody fusion was graded on the X-ray and CT images at the follow-up time.
RESULTS
There were 165 patients in this study. There were significant differences in the mean age, mean score, HIS and SSA between the groups at the different follow-up times. There were significant differences in the concentrations of serum Ca2 + , OC, β-CTX, 25-OH VD and PINP at the sixth month after surgery between the groups. There were significant differences in the concentrations of serum Ca2 + , β-CTX and 25-OH VD between the pre-surgery and at six months after surgery in Group B and β-CTX and 25-OH VD in Group C. There was a significant difference in the degree of fusion between Group B and C (χ2= 5.6243, P< 0.05).
CONCLUSION
In elderly patients with LIF and osteoporosis, anti-osteoporosis therapy could reduce bone resorption and thus facilitate fusion. Anti-osteoporosis medication tends to enhance radiological, functional, and fusion short-term outcomes.
PubMed: 38607748
DOI: 10.3233/BMR-230381 -
Experimental and Therapeutic Medicine May 2024Long-term hypertension can lead to hypertensive heart disease, which ultimately progresses to heart failure. As an angiotensin receptor blocker antihypertensive drug,...
Long-term hypertension can lead to hypertensive heart disease, which ultimately progresses to heart failure. As an angiotensin receptor blocker antihypertensive drug, allisartan can control blood pressure, and improve cardiac remodeling and cardiac dysfunction caused by hypertension. The aim of the present study was to investigate the protective effects of allisartan on the heart of spontaneously hypertensive rats (SHRs) and the underlying mechanisms. SHRs were used as an animal model of hypertensive heart disease and were treated with allisartan orally at a dose of 25 mg/kg/day. The blood pressure levels of the rats were continuously monitored, their body and heart weights were measured, and their cardiac structure and function were evaluated using echocardiography. Wheat germ agglutinin staining and Masson trichrome staining were employed to assess the morphology of the myocardial tissue. In addition, transcriptome and proteome analyses were performed using the Solexa/Illumina sequencing platform and tandem mass tag technology, respectively. Immunofluorescence co-localization was conducted to analyze Nrf2 nuclear translocation, and TUNEL was performed to detect the levels of cell apoptosis. The protein expression levels of pro-collagen I, collagen III, phosphorylated (p)-AKT, AKT, p-PI3K and PI3K, and the mRNA expression levels of Col1a1 and Col3a1 were determined by western blotting and reverse transcription-quantitative PCR, respectively. Allisartan lowered blood pressure, attenuated cardiac remodeling and improved cardiac function in SHRs. In addition, allisartan alleviated cardiomyocyte hypertrophy and cardiac fibrosis. Allisartan also significantly affected the 'pentose phosphate pathway', 'fatty acid elongation', 'valine, leucine and isoleucine degradation', 'glutathione metabolism', and 'amino sugar and nucleotide sugar metabolism' pathways in the hearts of SHRs, and upregulated the expression levels of GSTM2. Furthermore, allisartan activated the PI3K-AKT-Nrf2 signaling pathway and inhibited cardiomyocyte apoptosis. In conclusion, the present study demonstrated that allisartan can effectively control blood pressure in SHRs, and improves cardiac remodeling and cardiac dysfunction. Allisartan may also upregulate the expression levels of GSTM2 in the hearts of SHRs and significantly affect glutathione metabolism, as determined by transcriptome and proteome analyses. The cardioprotective effect of allisartan may be mediated through activation of the PI3K-AKT-Nrf2 signaling pathway, upregulation of GSTM2 expression and reduction of cardiomyocyte apoptosis in SHRs.
PubMed: 38590561
DOI: 10.3892/etm.2024.12508 -
Journal of Bone and Mineral Research :... Apr 2024Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require...
Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered parathyroid hormone (PTH) tablet on serum markers of bone formation [N-terminal propeptide of Type I procollagen (PINP) and osteocalcin (OC)] and bone resorption [crosslinked C-telopeptide (CTX)], bone mineral density (BMD) and safety in postmenopausal women with low BMD or osteoporosis. In this 6-month, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5 mg or placebo daily. Biochemical markers were assessed at 1, 2, 3 and 6 months and BMD of lumbar spine, total hip and femoral neck was measured at 6 months. Biochemical marker changes were dose dependent with minimal or no effect at the two lowest doses. At the highest dose (2.5 mg once daily), serum PINP and OC levels increased 30% within 1 month after oral PTH initiation (p < 0.0001), remained elevated through 3 months and were back to baseline at 6 months. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6 months respectively (both p ≤ 0.02). At 6 months, 2.5 mg tablets increased mean BMD vs placebo of the lumbar spine by 2.7%, total hip by 1.8%, and femoral neck by 2.8% (all p ≤ 0.01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.
PubMed: 38578978
DOI: 10.1093/jbmr/zjae057 -
JBMR Plus May 2024Calcitriol circulates at low levels in normal human and rodent fetuses, in part due to increased 24-hydroxylation of calcitriol and 25-hydroxyvitamin D by 24-hydroxylase...
Calcitriol circulates at low levels in normal human and rodent fetuses, in part due to increased 24-hydroxylation of calcitriol and 25-hydroxyvitamin D by 24-hydroxylase (CYP24A1). Inactivating mutations of cause high postnatal levels of calcitriol and the human condition of infantile hypercalcemia type 1, but whether the fetus is disturbed by the loss of CYP24A1 is unknown. We hypothesized that loss of in fetal mice will cause high calcitriol, hypercalcemia, and increased placental calcium transport. The mice were mated to create pregnancies with wildtype, , and null fetuses. The null fetuses were hypercalcemic, modestly hypophosphatemic (compared to fetuses only), with 3.5-fold increased calcitriol, 4-fold increased fibroblast growth factor 23 (FGF23), and unchanged parathyroid hormone. The quantitative RT-PCR confirmed the absence of and 2-fold increases in , sodium-calcium exchanger type 1, and calcium-sensing receptor in null placentas but not in fetal kidneys; these changes predicted an increase in placental calcium transport. However, placental Ca and P transport were unchanged in null fetuses. Fetal ash weight and mineral content, placental weight, crown-rump length, and skeletal morphology did not differ among the genotypes. Serum procollagen 1 intact N-terminal propeptide and bone expression of sclerostin and were reduced while calcitonin receptor was increased in nulls. In conclusion, loss of in fetal mice causes hypercalcemia, modest hypophosphatemia, and increased FGF23, but no alteration in skeletal development. Reduced incorporation of calcium into bone may contribute to the hypercalcemia without causing a detectable decrease in the skeletal mineral content. The results predict that human fetuses bearing homozygous or compound heterozygous inactivating mutations of will also be hypercalcemic in utero but with normal skeletal development.
PubMed: 38577520
DOI: 10.1093/jbmrpl/ziae012 -
The Journal of Clinical Investigation Apr 2024BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific... (Clinical Trial)
Clinical Trial
BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).
Topics: Humans; Biomarkers; Male; Female; Child; Child, Preschool; Respiratory Distress Syndrome; Infant; Inflammation; Prospective Studies; Adolescent; Multiple Organ Failure; Cytokines
PubMed: 38573766
DOI: 10.1172/JCI177896 -
Journal of Ethnopharmacology Jul 2024Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat...
ETHNOPHARMACOLOGICAL RELEVANCE
Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood.
AIM OF THE STUDY
To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites.
MATERIALS AND METHODS
C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type Ⅰ amino-terminal peptide (PⅠNP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites.
RESULTS
BX improved OP in OVX mice by increasing BMD, BV/TV, serum PⅠNP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group, Blautia, Rs-E47_termite_group, UCG-009, and Clostridia_UCG-014, were identified as the intrinsic link between GM and metabolites.
CONCLUSIONS
The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP.
Topics: Animals; Psoralea; Female; Mice, Inbred C57BL; Ovariectomy; Osteoporosis; Coumarins; Gastrointestinal Microbiome; Mice; Bone Density; Metabolomics; Disease Models, Animal; Fruit; Multiomics
PubMed: 38565407
DOI: 10.1016/j.jep.2024.118130 -
Endocrine and Metabolic Science Mar 2024Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the...
Prenatal but not continued postpartum vitamin D supplementation reduces maternal bone resorption as measured by C-terminal telopeptide of type 1 collagen without effects on other biomarkers of bone metabolism.
Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the Maternal Vitamin D for Infant Growth (MDIG) trial in Dhaka, Bangladesh, we aimed to investigate the effects of prenatal and postpartum vitamin D supplementation on circulating biomarkers of bone formation and resorption at delivery and 6 months postpartum. MDIG trial participants were randomized to receive a prenatal;postpartum regimen of placebo or vitamin D (IU/week) as either 0;0 (Group A), 4200;0 (B), 16,800;0 (C), 28,000;0 (D) or 28,000;28,000 (E) from 17 to 24 weeks' gestation to 6 months postpartum. As this sub-study was not pre-planned, the study sample included MDIG participants who had data for at least 1 biomarker of interest at delivery or 6 months postpartum, with a corresponding baseline measurement ( = 690; 53 % of 1300 enrolled trial participants). Biomarkers related to bone turnover were measured in maternal venous blood samples collected at enrolment, delivery, and 6 months postpartum: osteoprotegerin (OPG), osteocalcin (OC), receptor activator nuclear factor kappa-B ligand (RANKL), fibroblast growth factor 23 (FGF23), procollagen type 1 N-terminal propeptide, (P1NP) and carboxy terminal telopeptide of type 1 collagen (CTx). Supplementation effects were expressed as percent differences between each vitamin D group and placebo with 95 % confidence intervals (95 % CI). Of 690 participants, 64 % had 25-hydroxyvitamin D concentrations (25OHD) <30 nmol/L and 94 % had 25OHD < 50 nmol/L at trial enrolment. At delivery, mean CTx concentrations were 27 % lower in group E versus placebo (95 % CI: -38, -13; < 0.001), adjusting for enrolment concentrations. However, at 6 months postpartum, CTx concentrations were not statistically different in group E versus placebo (14 %; 95 % CI: -5.3, 37; = 0.168), adjusting for delivery CTx concentrations. Effects on other biomarkers at delivery or postpartum were not statistically significant. In conclusion, prenatal high-dose vitamin D supplementation reduced bone resorption during pregnancy, albeit by only one biomarker, and without evidence of a sustained effect in the postpartum period. However, further evidence is needed to substantiate potential maternal bone health benefits of vitamin D in the postpartum period.
PubMed: 38558882
DOI: 10.1016/j.endmts.2023.100154 -
Endocrine Practice : Official Journal... Jun 2024Advances in the management of people with type 1 diabetes (T1D) led to longer life expectancy, but with it an aging population with age-associated conditions. While... (Review)
Review
Advances in the management of people with type 1 diabetes (T1D) led to longer life expectancy, but with it an aging population with age-associated conditions. While macrovascular and microvascular complications are widely recognized, bone fragility has received considerably less attention, although fractures lead to high morbidity and mortality. Hip fracture risk is up to sixfold higher in T1D than in nondiabetic controls and significantly higher than in type 2 diabetes. Hip fractures occur at a younger age, and the consequences are worse. The risk of nonvertebral fractures is also significantly increased. Altered bone quality is a major underlying mechanism. Areal BMD measured by DXA underestimates fracture risk. BMD testing is recommended in T1D patients with poor glycemic control and/or microvascular complications. Trabecular bone score is mildly reduced, and its ability to predict fractures in T1D is unknown. Bone turnover markers, particularly procollagen type 1 N-terminal propeptide, are suppressed and do not predict fracture risk in T1D. T1D-related risk factors for fractures include disease onset at age <20 years, longer disease duration, HbA1c ≥8%, hypoglycemic episodes and microvascular complications. Data regarding the efficacy of therapeutic interventions to prevent or treat skeletal fragility in T1D is scant. Adequate calcium and vitamin D intake and fall prevention are recommended. Antiosteoporosis therapies are recommended in T1D patients with previous hip or vertebral fragility fracture, more than 1 other fragility fracture, BMD T-score < -2.5 at the femoral neck or spine, and increased FRAX score. Fracture risk assessment needs to be part of the management of people with T1D.
Topics: Humans; Diabetes Mellitus, Type 1; Fractures, Bone; Bone Density; Adult; Risk Factors; Osteoporosis
PubMed: 38556079
DOI: 10.1016/j.eprac.2024.03.392 -
Current Issues in Molecular Biology Mar 2024Inflammation and collagen-degrading enzymes' overexpression promote collagen decomposition, which affects the structural integrity of the extracellular matrix. The...
Inflammation and collagen-degrading enzymes' overexpression promote collagen decomposition, which affects the structural integrity of the extracellular matrix. The polysaccharide and peptide extracts of the green alga () have been proven to have anti-inflammatory, wound healing, and antioxidant effects in vivo and in vitro. However, the biological properties of the non-water-soluble components of are still unknown. In the present study, we demonstrated the higher effective anti-inflammatory functions of ethyl acetate (EA) extract than water extract up to 16-30% in LPS-induced HaCaT cells, including reducing the production of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Furthermore, the excellent collagen homeostasis effects from were proven by suppressing the matrix metalloproteinase-1 (MMP-1) secretion, enhancing type 1 procollagen and collagen expressions dose-dependently in WS1 cells. Moreover, using UHPLC-QTOF-MS analysis, four terpenoids, siphonaxanthin, caulerpenyne, caulerpal A, and caulerpal B, were identified and may be involved in the superior collagen homeostasis and anti-inflammatory effects of the EA extract.
PubMed: 38534786
DOI: 10.3390/cimb46030170