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1.
Front Cell Dev Biol ; 12: 1449232, 2024.
Article in English | MEDLINE | ID: mdl-39239557

ABSTRACT

Despite recent advances in cancer diagnostics and treatment, the mortality associated with lung cancer is still the highest in the world. Late-stage diagnosis, often accompanied by metastasis, is a major contributor to the high mortality rates, emphasizing the urgent need for reliable and readily accessible diagnostic tools that can detect biomarkers unique to lung cancer. Circulating factors, such as circulating tumor DNA and extracellular vesicles, from liquid biopsy have been recognized as diagnostic or prognostic markers in lung cancer. Numerous clinical studies are currently underway to investigate the potential of circulating tumor DNA, circulating tumor RNA, exosomes, and exosomal microRNA within the context of lung cancer. Those clinical studies aim to address the poor diagnostics and limited treatment options for lung cancer, with the ultimate goal of developing clinical markers and personalized therapies. In this review, we discuss the roles of each circulating factor, its current research status, and ongoing clinical studies of circulating factors in non-small cell lung cancer. Additionally, we discuss the circulating factors specifically found in lung cancer stem cells and examine approved diagnostic assays designed to detect circulating biomarkers in lung cancer patients.

2.
JAMA Neurol ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39226035

ABSTRACT

Importance: A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion. Objective: To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus. Design, Setting, and Participants: This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration. Exposures: Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days). Main Outcomes and Measures: A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment. Results: Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not. Conclusions and Relevance: Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.

3.
Adv Sci (Weinh) ; : e2403245, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39119926

ABSTRACT

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture-induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms.

4.
Small ; : e2405493, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39087376

ABSTRACT

Simultaneous monitoring of critical parameters (e.g., pressure, shear, and temperature) at bony prominences is essential for the prevention of pressure injuries in a systematic manner. However, the development of wireless sensor array for accurate mapping of risk factors has been limited due to the challenges in the convergence of wireless technologies and wearable sensor arrays with a thin and small form factor. Herein, a battery-free, wireless, miniaturized multi-modal sensor array is introduced for continuous mapping of pressure, shear, and temperature at skin interfaces. The sensor array includes an integrated pressure and shear sensor consisting of 3D strain gauges and micromachined components. The mechanically decoupled design of the integrated sensor enables reliable data acquisition of pressure and shear at skin interfaces without the need for additional data processing. The sensor platform enables the analysis of interplay among localized pressure, shear, and temperature in response to changes in the patient's movement, posture, and bed inclination. The validation trials using a novel combination of wireless sensor arrays and customized pneumatic actuator demonstrate the efficacy of the platform in continuous monitoring and efficient redistribution of pressure and shear without repositioning, thereby improving the patient's quality of life.

5.
Mol Oncol ; 2024 Aug 11.
Article in English | MEDLINE | ID: mdl-39129344

ABSTRACT

Dysregulation of epidermal growth factor receptor (EGFR) is one of the most common mechanisms associated with the pathogenesis of various cancers. Mitogen-inducible gene 6 [MIG6; also known as ERBB receptor feedback inhibitor 1 (ERRFI1)], identified as a feedback inhibitor of EGFR, negatively regulates EGFR by directly inhibiting its kinase activity and facilitating its internalization, subsequently leading to degradation. Despite its proposed role as an EGFR-dependent tumor suppressor, the functional consequences and clinical relevance in cancer etiology remain incompletely understood. Here, we identify that the stoichiometric balance between MIG6 and EGFR is crucial in promoting EGFR-dependent oncogenic growth in various experimental model systems. In addition, a subset of ERRFI1 (the official gene symbol of MIG6) mutations exhibit impaired ability to suppress the enzymatic activation of EGFR at multiple levels. In summary, our data suggest that decreased or loss of MIG6 activity can lead to abnormal activation of EGFR, potentially contributing to cellular transformation. We propose that the mutation status of ERRFI1 and the expression levels of MIG6 can serve as additional biomarkers for guiding EGFR-targeted cancer therapies, including glioblastoma.

6.
Korean J Fam Med ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39164030

ABSTRACT

Background: The liver plays an important role in gonadal steroid hormone metabolism, which can affect reproductive health, including the menstrual cycle. However, evidence from large population-based studies is limited. Therefore, this study aimed to investigate the association between liver function markers and menstrual cycle irregularities in premenopausal Korean women using nationwide data. Methods: This study analyzed Data from the Korea National Health and Nutrition Examination Survey 2010-2011. We investigated 3,045 premenopausal women aged 19-59 years. Liver function markers including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase, and fatty liver index were analyzed. Multivariable logistic regression analysis was performed to investigate the association between liver function markers and menstrual cycle irregularity while adjusting for confounding factors. Values were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analysis was also performed. Results: Baseline characteristic analysis showed that approximately 14.4% of the study population experienced menstrual cycle irregularity. The mean age was 34.5±0.7 years. The highest quartile of serum ALT and AST levels showed significantly higher ORs for menstrual cycle irregularity (adjusted OR, 1.83; 95% CI, 1.26-2.64 and adjusted OR, 1.67; 95% CI, 1.17-2.39, respectively). A similar result was observed in the subgroup analysis. Conclusion: Liver function markers were positively associated with menstrual cycle irregularities. In clinical settings, women of reproductive age with relatively decreased liver function should be considered for regular followup of their reproductive health status.

7.
Molecules ; 29(16)2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39203042

ABSTRACT

Nanofiber (NF) membrane systems that can provide cascade catalytic reaction and ferroptosis induction were developed for oral cancer therapy. Glucose oxidase (GOx) and aminoferrocene (AF) were introduced into the NF system for glucose deprivation/H2O2 generation and OH radical generation, respectively. GOx offers starvation therapy and AF (including iron) provides chemodynamic therapy/ferroptosis for combating oral cancer. GOx (water-soluble) and AF (poorly water-soluble) molecules were successfully entrapped in the NF membrane via an electrospinning process. GOx and AF were incorporated into the polyvinyl alcohol (PVA)-based NF, resulting in PVA/GOx/AF NF with fast disintegration and immediate drug-release properties. In oral squamous cell carcinoma (YD-9 cells), the PVA/GOx/AF NF group exhibited higher cytotoxicity, antiproliferation potential, cellular ROS level, apoptosis induction, lipid ROS level, and malondialdehyde level compared to the other NF groups. The electrospun PVA/GOx/AF NF can be directly applied to oral cancer without causing pain, offering starvation/chemodynamic therapy and ferroptosis induction.


Subject(s)
Carcinoma, Squamous Cell , Ferroptosis , Hydroxyl Radical , Mouth Neoplasms , Nanofibers , Humans , Mouth Neoplasms/drug therapy , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Nanofibers/chemistry , Ferroptosis/drug effects , Hydroxyl Radical/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Glucose Oxidase/metabolism , Glucose Oxidase/chemistry , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Polyvinyl Alcohol/chemistry , Cell Proliferation/drug effects
8.
J Mater Chem B ; 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39206756

ABSTRACT

In clinical practice, determining programmed death-ligand 1 (PD-L1) expression is crucial for selecting patients and monitoring immune checkpoint blockade therapies. Currently, PD-L1 expression is quantified using immunohistochemistry (IHC). However, IHC-based methods do not capture the heterogeneous and dynamic nature of PD-L1 expression. Thus, there is a pressing need for a rapid and efficient method for monitoring PD-L1 expression both in vitro and in vivo, which would considerably aid in prognosis and treatment selection. In this study, we present for the first time an activatable near-infrared (NIR) fluorescence imaging probe (Q-Atezol) for the real-time monitoring of PD-L1 expression in vitro and in vivo. The ability of Q-Atezol to detect PD-L1 expression quickly and in real-time was evaluated in both tumor spheroid and lung cancer xenograft models. An always-on optical probe (ON-Atezol) was synthesized and tested for comparison. In vivo NIR fluorescence imaging studies were conducted on A549 and H1975 tumor-bearing mice, and their tumor-to-background ratios (TBRs) were analyzed. The quenched NIR fluorescence of Q-Atezol is activated upon binding to PD-L1 proteins on the surface of cancer cells, thereby enabling PD-L1 detection in the three-dimensional (3D) tumor spheroids without a washing step. Notably, PD-L1-positive H1975 tumors were clearly visualized with a high TBR 6 hours after Q-Atezol injection, whereas ON-Atezol treatment could not detect H1975 tumors even 24 hours post-injection. The activatable fluorescence probe Q-Atezol demonstrated great potential as an exceptional sensor for assessing PD-L1 expression in 3D cell structures and for in vivo applications.

9.
Pharmaceutics ; 16(8)2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39204379

ABSTRACT

The efficacy of glioblastoma treatment is closely associated with complete tumor resection. However, conventional surgical techniques often result in incomplete removal, leading to poor prognosis. A major challenge is the accurate delineation of tumor margins from healthy tissues. Imaging-guided surgery, particularly using fluorescent probes, is a promising solution for intraoperative guidance. The recently developed 'always-on' types of targeted fluorescence probes generate signals irrespective of their presence in tumor cells or in blood circulation, hampering their effectiveness. Here, we propose a novel activatable fluorescence imaging probe, Q-cRGD, that targets glioma cells via the specific binding of the cyclic Arg-Gly Asp-containing pentapeptide (cRGD) to integrins. The Q-cRGD probe was synthesized by conjugating a near-infrared (NIR) dye to a tryptophan quencher via a disulfide linkage, including a cRGD-targeting ligand. This activatable probe remained inactive until the redox-responsive cleavage of the disulfide linkage occurred within the target cell. The zwitterionic nature of NIR dyes minimizes nonspecific interactions with serum proteins, thereby enhancing the tumor-to-background signal ratio (TBR). An in vivo fluorescence imaging study demonstrated a TBR value of 2.65 within 3 h of the intravenous injection of Q-cRGD, confirming its potential utility in imaging-guided brain cancer surgery.

10.
Lipids Health Dis ; 23(1): 272, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39198834

ABSTRACT

BACKGROUND AND PURPOSE: Genome-wide association studies (GWAS) of metabolic syndrome (MetS) have predominantly focused on non-Asian populations, with limited representation from East Asian cohorts. Moreover, previous GWAS analyses have primarily emphasized the significance of top single nucleotide polymorphisms (SNPs), poorly explaining other SNP signals in linkage disequilibrium. This study aimed to reveal the interaction between rs651821 and rs2266788, the principal variants of apolipoprotein A5 (APOA5), within the most significant loci identified through GWAS on MetS. METHODS: GWAS on MetS and its components was conducted using the data from the Korean Genome and Epidemiology Study (KoGES) city cohort comprising 58,600 individuals with available biochemical, demographic, lifestyle factors, and the most significant APOA5 locus was analyzed further in depth. RESULTS: According to GWAS of MetS and its diagnostic components, a significant association between the APOA5 SNPs rs651821/rs2266788 and MetS/triglycerides/high-density lipoprotein phenotypes was revealed. However, a conditional analysis employing rs651821 unveiled a reversal in the odds ratio for rs2266788. Therefore, rs651821 and rs2266788 emerged as independent and opposing signals in the extended GWAS analysis, i.e., the multilayered effects. Further gene-environment interaction analyses regarding lifestyle factors such as smoking, alcohol consumption, and physical activity underscored these multilayered effects. CONCLUSION: This study unveils the intricate interplay between rs651821 and rs2266788 derived from MetS GWAS. Removing the influence of lead SNP reveals an independent protective signal associated with rs2266788, suggesting a multilayered effect between these SNPs. These findings underline the need for novel perspectives in future MetS GWAS.


Subject(s)
Apolipoprotein A-V , Genome-Wide Association Study , Metabolic Syndrome , Polymorphism, Single Nucleotide , Humans , Apolipoprotein A-V/genetics , Metabolic Syndrome/genetics , Male , Middle Aged , Female , Republic of Korea/epidemiology , Asian People/genetics , Genetic Predisposition to Disease , Linkage Disequilibrium , Adult , Aged , Triglycerides/blood , Lipoproteins, HDL/genetics , East Asian People
11.
Nat Immunol ; 25(9): 1742-1753, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39164477

ABSTRACT

The differentiation and specificity of human CD4+ T follicular helper cells (TFH cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4+ TFH cell response. The first vaccination induced an increase in the frequency of circulating TFH (cTFH) and LN TFH cells at week 1 postvaccination. This increase was transient for cTFH cells, whereas the LN TFH cells further expanded during week 2 and remained elevated in frequency for at least 3 months. We observed several distinct subsets of TFH cells in the LN, including pre-TFH cells, memory TFH cells, germinal center (GC) TFH cells and interleukin-10+ TFH cell subsets beginning at baseline and at all time points postvaccination. The shift toward a GC TFH cell phenotype occurred with faster kinetics after the second vaccine compared to the first vaccine. We identified several influenza-specific TFH cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each TFH cell state was attainable within a clonal lineage. Thus, human TFH cells form a durable and dynamic multitissue network.


Subject(s)
Cell Differentiation , Germinal Center , Influenza Vaccines , Influenza, Human , T Follicular Helper Cells , Vaccination , Humans , Influenza Vaccines/immunology , T Follicular Helper Cells/immunology , Influenza, Human/immunology , Influenza, Human/prevention & control , Germinal Center/immunology , Cell Differentiation/immunology , Lymph Nodes/immunology , Adult , Female , Male , Middle Aged , Interleukin-10/immunology , Interleukin-10/metabolism , Immunologic Memory/immunology , T-Lymphocytes, Helper-Inducer/immunology , Young Adult
13.
Article in English | MEDLINE | ID: mdl-38986517

ABSTRACT

Objective: Stereoelectroencephalography (SEEG) is increasingly being recognized as an important invasive modality for presurgical evaluation of epilepsy. This study focuses on the clinical and technical considerations of SEEG investigations when using conventional frame-based stereotaxy, drawing on institutional experience and a comprehensive review of relevant literature. Methods: This retrospective observational study encompassed the surgical implantation of 201 SEEG electrodes in 16 epilepsy patients using a frame-based stereotactic instrument at a single tertiary-level center. We provide detailed descriptions of the operative procedures and technical nuances for bilateral and multiple SEEG insertions, along with several illustrative cases. Additionally, we present a literature review on the technical aspects of the SEEG procedure, discussing its clinical implications and potential risks. Results: Frame-based SEEG electrode placements were successfully performed through sagittal arc application, with the majority (81.2%) of cases being bilateral and involving up to 18 electrodes in a single operation. The median skin-to-skin operation time was 162 minutes (interquartile range [IQR], 145-200), with a median of 13 minutes (IQR, 12-15) per electrode placement for time efficiency. There were two occurrences (1.0%) of electrode misplacement and one instance (0.5%) of a postoperative complication, which manifested as a delayed intraparenchymal hemorrhage. Following SEEG investigation, 11 patients proceeded with surgical intervention, resulting in favorable seizure outcomes for nine (81.8%) and complete remission for eight cases (72.7%). Conclusion: Conventional frame-based stereotactic techniques remain a reliable and effective option for bilateral and multiple SEEG electrode placements. While SEEG is a suitable approach for selected patients who are strong candidates for epilepsy surgery, it is important to remain vigilant concerning the potential risks of electrode misplacement and hemorrhagic complications.

14.
Front Neurol ; 15: 1427142, 2024.
Article in English | MEDLINE | ID: mdl-39022726

ABSTRACT

Background: Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. Methods: This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. Discussion: This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT06270238.

15.
Cancer Res Treat ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010797

ABSTRACT

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea's cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

16.
Int J Mol Sci ; 25(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39000349

ABSTRACT

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.


Subject(s)
Aorta , Cyclic GMP , Emulsions , Labetalol , Nitric Oxide Synthase Type III , Vasodilation , Animals , Vasodilation/drug effects , Rats , Aorta/drug effects , Aorta/metabolism , Labetalol/pharmacology , Male , Nitric Oxide Synthase Type III/metabolism , Cyclic GMP/metabolism , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Rats, Sprague-Dawley , Humans , Lipids , Phosphorylation/drug effects , Calcium/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism
17.
Sci Rep ; 14(1): 15605, 2024 07 06.
Article in English | MEDLINE | ID: mdl-38971850

ABSTRACT

Low blood pressure (BP) is associated with poor outcomes in patients with heart failure (HF). We investigated the influence of initial BP on the prognosis of HF patients at admission, and prescribing patterns of HF medications, such as angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and beta-blockers (BB). Data were sourced from a multicentre cohort of patients admitted for acute HF. Patients were grouped into heart failure reduced ejection fraction (HFrEF) and HF mildly reduced/preserved ejection fraction (HFmrEF/HFpEF) groups. Initial systolic and diastolic BPs were categorized into specific ranges. Among 2778 patients, those with HFrEF were prescribed ACEi, ARB, or BB at discharge, regardless of their initial BP. However, medication use in HFmrEF/HFpEF patients tended to decrease as BP decreased. Lower initial BP in HFrEF patients correlated with an increased incidence of all-cause death and composite clinical events, including HF readmission or all-cause death. However, no significant differences in clinical outcomes were observed in HFmrEF/HFpEF patients according to BP. Initial systolic (< 120 mmHg) and diastolic (< 80 mmHg) BPs were independently associated with a 1.81-fold (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.349-2.417, p < 0.001) and 2.24-fold (OR 2.24, 95% CI 1.645-3.053, p < 0.001) increased risk of long-term mortality in HFrEF patients, respectively. In conclusion, low initial BP in HFrEF patients correlated with adverse clinical outcomes, and BP < 120/80 mmHg independently increased mortality. However, this relationship was not observed in HFmrEF/HFpEF patients.


Subject(s)
Heart Failure , Humans , Heart Failure/physiopathology , Heart Failure/drug therapy , Heart Failure/mortality , Male , Female , Aged , Prognosis , Hypotension/physiopathology , Blood Pressure , Acute Disease , Middle Aged , Aged, 80 and over , Stroke Volume , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use
18.
Biomedicines ; 12(7)2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39062186

ABSTRACT

Stiffness and adhesions following rotator cuff tears (RCTs) are common complications that negatively affect surgical outcomes and impede healing, thereby increasing the risk of morbidity and failure of surgical interventions. Tissue engineering, particularly through the use of nanofiber scaffolds, has emerged as a promising regenerative medicine strategy to address these complications. This review critically assesses the efficacy and limitations of nanofiber-based methods in promoting rotator cuff (RC) regeneration and managing postrepair stiffness and adhesions. It also discusses the need for a multidisciplinary approach to advance this field and highlights important considerations for future clinical trials.

19.
J Pers Med ; 14(7)2024 Jun 22.
Article in English | MEDLINE | ID: mdl-39063927

ABSTRACT

BACKGROUND: Femoral fractures often lead to complications such as altered pulmonary hemodynamics. Right ventricular global longitudinal strain (RV GLS), which correlates with pulmonary hemodynamics, indicates the subclinical function of the right ventricle (RV). This study aimed to investigate the predictive value of RV GLS for the risk of adverse clinical composite outcomes in patients with femoral fractures. METHODS: Data were obtained from a prospective single-center cohort of patients hospitalized for femoral fractures and followed up for at least 1 year between March 2021 and October 2022. The primary outcome was the development of an adverse composite clinical event, which included pneumonia, pulmonary oedema or effusion, pulmonary thromboembolism, and all-cause mortality within the 1-year period following surgery. RESULTS: Among the 163 patients, 36 (22.09%) experienced adverse composite clinical events during 1-year follow-up. The adverse outcome group demonstrated poorer RV GLS and RV free wall strain values than the non-adverse outcome group. The optimal cut-off value of RV GLS for predicting composite adverse clinical events was -12.55%. The cumulative composite event-free survival rate was significantly lower in the RV GLS ≥ -12.55% group (log-rank p-value = 0.003). After adjusting for confounding factors, multivariate Cox proportional hazards regression analyses showed that RV GLS ≥ -12.55% independently increased the risk of composite adverse clinical events by 2.65-fold. CONCLUSIONS: Poor RV GLS is a significant predictor of adverse clinical outcomes in patients with femoral fractures. Specifically, an RV GLS value of ≥ -12.55% indicated a substantially increased risk of adverse events.

20.
Clin Hypertens ; 30(1): 16, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38945999

ABSTRACT

BACKGROUND: The current standard approach to measuring home blood pressure (BP) involves taking measurements while sitting in a chair. In cultures where floor sitting is common, including Korea, assessing BP while sitting on the floor would be more feasible. However, there is still a lack of research investigating whether BP measurements obtained while seated in a chair and while sitting on the floor can be regarded as interchangeable. The aim of the study was to evaluate whether there is a difference between BP measurements taken while sitting in a chair and while sitting on the floor in a Korean adult. METHODS: Among the participants who visited for evaluation of pulse wave velocity, a total of 116 participants who agreed to participate in the study were randomly selected. All subjects rested for 5 min, and BP measurements were taken at 1-min intervals according to a randomly assigned order of standard method (chair-sitting) and BP in a seated on the floor (floor-sitting). RESULTS: Of the 116 participants, the median age was 68 (with an interquartile range of 59 to 75), and 82% were men. There were no significant differences in systolic BP (SBP, 129.1 ± 17.8 mmHg in chair-sitting and 130.1 ± 18.9 mmHg in floor-sitting, P = 0.228) and diastolic BP (DBP, 73.9 ± 11.4 mmHg in chair-sitting and 73.7 ± 11.4 mmHg in floor-sitting, P = 0.839) between the two positions. In addition, there was a high level of agreement between BP measurements taken in the two positions (intraclass correlation coefficients: 0.882 for SBP and 0.890 for DBP). CONCLUSION: These findings provide important insights into securing the reliability of home BP measurements through the commonly practiced floor-sitting posture in cultures where floor sitting is common. Furthermore, this could serve as substantial evidence for providing specific home BP measurement guidelines to patients who adhere to a floor-sitting lifestyle.

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