Exploring Cardiac Exosomal RNAs of Acute Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI), often a frequent symptom of coronary artery disease (CAD), is a leading cause of death and disability worldwide. Acute myocardial infarction (AMI), a major form of cardiovascular disease, necessitates a deep understanding of its complex pathophysiology to develop innovative therapeutic strategies. Exosomal RNAs (exoRNA), particularly microRNAs (miRNAs) within cardiac tissues, play a critical role in intercellular communication and pathophysiological processes of AMI. METHODS: This study aimed to delineate the exoRNA landscape, focusing especially on miRNAs in animal models using high-throughput sequencing. The approach included sequencing analysis to identify significant miRNAs in AMI, followed by validation of the functions of selected miRNAs through in vitro studies involving primary cardiomyocytes and fibroblasts. RESULTS: Numerous differentially expressed miRNAs in AMI were identified using five mice per group. The functions of 20 selected miRNAs were validated through in vitro studies with primary cardiomyocytes and fibroblasts. CONCLUSIONS: This research enhances understanding of post-AMI molecular changes in cardiac tissues and investigates the potential of exoRNAs as biomarkers or therapeutic targets. These findings offer new insights into the molecular mechanisms of AMIs, paving the way for RNA-based diagnostics and therapeutics and therapies and contributing to the advancement of cardiovascular medicine.

Cost and time-efficient construction of a 3'-end mRNA library from unpurified bulk RNA in a single tube.

The major drawbacks of RNA sequencing (RNA-seq), a remarkably accurate transcriptome profiling method, is its high cost and poor scalability. Here, we report a highly scalable and cost-effective method for transcriptomics profiling called Bulk transcriptOme profiling of cell Lysate in a single poT (BOLT-seq), which is performed using unpurified bulk 3'-end mRNA in crude cell lysates. During BOLT-seq, RNA/DNA hybrids are directly subjected to tagmentation, and second-strand cDNA synthesis and RNA purification are omitted, allowing libraries to be constructed in 2 h of hands-on time. BOLT-seq was successfully used to cluster small molecule drugs based on their mechanisms of action and intended targets. BOLT-seq competes effectively with alternative library construction and transcriptome profiling methods.

Effects of Melatonin, GM-CSF, IGF-1, and LIF in Culture Media on Embryonic Development: Potential Benefits of Individualization.

The implantation of good-quality embryos to the receptive endometrium is essential for successful live birth through in vitro fertilization (IVF). The higher the quality of embryos, the higher the live birth rate per cycle, and so efforts have been made to obtain as many high-quality embryos as possible after fertilization. In addition to an effective controlled ovarian stimulation process to obtain high-quality embryos, the composition of the embryo culture medium in direct contact with embryos in vitro is also important. During embryonic development, under the control of female sex hormones, the fallopian tubes and endometrium create a microenvironment that supplies the nutrients and substances necessary for embryos at each stage. During this process, the development of the embryo is finely regulated by signaling molecules, such as growth factors and cytokines secreted from the epithelial cells of the fallopian tube and uterine endometrium. The development of embryo culture media has continued since the first successful human birth through IVF in 1978. However, there are still limitations to mimicking a microenvironment similar to the reproductive organs of women suitable for embryo development in vitro. Efforts have been made to overcome the harsh in vitro culture environment and obtain high-quality embryos by adding various supplements, such as antioxidants and growth factors, to the embryo culture medium. Recently, there has been an increase in the number of studies on the effect of supplementation in different clinical situations such as old age, recurrent implantation failure (RIF), and unexplained infertility; in addition, anticipation of the potential benefits from individuation is rising. This article reviews the effects of representative supplements in culture media on embryo development.

Enhanced Osteocyte Differentiation: Cathepsin D and L Secretion by Human Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) have the potential to differentiate into bone, cartilage, fat, and neural cells and promote tissue regeneration and healing. It is known that they can have variable responses to hypoxic conditions. In the present study, we aimed to explore diverse changes in the cells and secretome of ASCs under a hypoxic environment over time and to present the possibility of ASCs as therapeutic agents from a different perspective. The expression differences of proteins between normoxic and hypoxic conditions (6, 12, or 24 h) were specifically investigated in human ASCs using 2-DE combined with MALDI-TOF MS analysis, and secreted proteins in ASC-derived conditioned media (ASC-derived CM) were examined by an adipokine array. In addition, genetic and/or proteomic interactions were assessed using a DAVID and miRNet functional annotation bioinformatics analysis. We found that 64 and 5 proteins were differentially expressed in hypoxic ASCs and in hypoxic ASC-derived CM, respectively. Moreover, 7 proteins among the 64 markedly changed spots in hypoxic ASCs were associated with bone-related diseases. We found that two proteins, cathepsin D (CTSD) and cathepsin L (CTSL), identified through an adipokine array independently exhibited significant efficacy in promoting osteocyte differentiation in bone-marrow-derived mesenchymal stem cells (BM-MSCs). This finding introduces a promising avenue for utilizing hypoxia-preconditioned ASC-derived CM as a potential therapeutic approach for bone-related diseases.

An Automatic-Vertical Profile Monitoring System for Fresh-Saline Water Zones in Coastal Aquifer.

Coastal aquifers are complex systems governed by fresh-saline water interactions and ocean tidal effects. The vertical electrical conductivity (EC) and temperature (T) are general indicators for detecting the fresh-saline water interface (FSI) and sea water intrusion in groundwater wells located in coastal aquifers. In this method brief, we developed a cost-effective Arduino-based automatic-vertical profile monitoring system (A-VPMS) to continuously record vertical EC and T in groundwater wells, with the aim of testing its effectiveness in spatiotemporal monitoring of the FSI in a coastal aquifer located in eastern Korea. By analyzing the high-density EC and T data obtained by the A-VPMS, we evaluated the characteristics of the FSI, such as depth and spatial distribution. Our established EC and T data collection method using the A-VPMS proved to be efficient and reliable, providing an excellent tool for fine-scale temporal and spatial understanding of sea water intrusion. The results of this study demonstrate the potential of the A-VPMS for continuous monitoring of the FSI in coastal aquifers, which is crucial for sustainable management of groundwater resources.

MARS2 drives metabolic switch of non-small-cell lung cancer cells via interaction with MCU.

Mitochondrial methionyl-tRNA synthetase (MARS2) canonically mediates the formation of fMet-tRNAifMet for mitochondrial translation initiation. Mitochondrial calcium uniporter (MCU) is a major gate of Ca2+ flux from cytosol into the mitochondrial matrix. We found that MARS2 interacts with MCU and stimulates mitochondrial Ca2+ influx. Methionine binding to MARS2 would act as a molecular switch that regulates MARS2-MCU interaction. Endogenous knockdown of MARS2 attenuates mitochondrial Ca2+ influx and induces p53 upregulation through the Ca2+-dependent CaMKII/CREB signaling. Subsequently, metabolic rewiring from glycolysis into pentose phosphate pathway is triggered and cellular reactive oxygen species level decreases. This metabolic switch induces inhibition of epithelial-mesenchymal transition (EMT) via cellular redox regulation. Expression of MARS2 is regulated by ZEB1 transcription factor in response to Wnt signaling. Our results suggest the mechanisms of mitochondrial Ca2+ uptake and metabolic control of cancer that are exerted by the key factors of the mitochondrial translational machinery and Ca2+ homeostasis.

A Low Concentration of Citreoviridin Prevents Both Intracellular Calcium Deposition in Vascular Smooth Muscle Cell and Osteoclast Activation In Vitro.

Vascular calcification (VC) and osteoporosis are age-related diseases and significant risk factors for the mortality of elderly. VC and osteoporosis may share common risk factors such as renin-angiotensin system (RAS)-related hypertension. In fact, inhibitors of RAS pathway, such as angiotensin type 1 receptor blockers (ARBs), improved both vascular calcification and hip fracture in elderly. However, a sex-dependent discrepancy in the responsiveness to ARB treatment in hip fracture was observed, possibly due to the estrogen deficiency in older women, suggesting that blocking the angiotensin signaling pathway may not be effective to suppress bone resorption, especially if an individual has underlying osteoclast activating conditions such as estrogen deficiency. Therefore, it has its own significance to find alternative modality for inhibiting both vascular calcification and osteoporosis by directly targeting osteoclast activation to circumvent the shortcoming of ARBs in preventing bone resorption in estrogen deficient individuals. In the present study, a natural compound library was screened to find chemical agents that are effective in preventing both calcium deposition in vascular smooth muscle cells (vSMCs) and activation of osteoclast using experimental methods such as Alizarin red staining and Tartrate-resistant acid phosphatase staining. According to our data, citreoviridin (CIT) has both an anti-VC effect and anti-osteoclastic effect in vSMCs and in Raw 264.7 cells, respectively, suggesting its potential as an effective therapeutic agent for both VC and osteoporosis.

Wireless dielectrophoresis trapping and remote impedance sensing via resonant wireless power transfer.

Nearly all biosensing platforms can be described using two fundamental steps-collection and detection. Target analytes must be delivered to a sensing element, which can then relay the transduced signal. For point-of-care technologies, where operation is to be kept simple, typically the collection step is passive diffusion driven-which can be slow or limiting under low concentrations. This work demonstrates an integration of both active collection and detection by using resonant wireless power transfer coupled to a nanogap capacitor. Nanoparticles suspended in deionized water are actively trapped using wireless dielectrophoresis and positioned within the most sensitive fringe field regions for wireless impedance-based detection. Trapping of 40 nm particles and larger is demonstrated using a 3.5 VRMS, 1 MHz radiofrequency signal delivered over a distance greater than 8 cm from the nanogap capacitor. Wireless trapping and release of 1 µm polystyrene beads is simultaneously detected in real-time over a distance of 2.5 cm from the nanogap capacitor. Herein, geometric scaling strategies coupled with optimal circuit design is presented to motivate combined collection and detection biosensing platforms amenable to wireless and/or smartphone operation.

High Mean Platelet Volume Is Associated with Cerebral White Matter Hyperintensities in Non-Stroke Individuals.

PURPOSE: The mean platelet volume (MPV) is regarded as a marker for thrombosis, atherosclerosis, and inflammation in various vascular diseases. However, it still remains unclear whether plasma MPV is associated with cerebral white matter hyperintensities (WMH) and cerebral microvascular pathology in the elderly population. MATERIALS AND METHODS: We examined whether MPV level is associated with the presence of cerebral WMH on brain magnetic resonance imaging from 870 non-stroke outpatient subjects. The subjects were divided into three groups according to the consecutive level of MPV (low T1, middle T2, and high T3 MPV tertile groups). To determine the association of MPV levels with the WMH, logistic regression and receiver operating characteristic curve analyses were conducted. RESULTS: Subjects with higher MPV level were older and more likely to have hypertension, diabetes mellitus, and low renal function. Cerebral WMH were more prevalent in subjects with higher MPV level. After adjusting for confounding factors, moderate to severe cerebral WMH were significantly associated with high MPV tertile level. This association remained significant after adjusting for other cerebral vascular pathologies. T2 [odds ratio (OR): 1.49, 95% confidence interval (CI): 1.03-2.15] and T3 MPV tertile groups (OR: 1.51, 95%CI: 1.04-2.20) had more cerebral WMH lesions compared to T1 MPV tertile group. In addition, the subjects with higher Fazekas scores showed higher MPV level (p=0.020). CONCLUSION: We found that high MPV level is independently associated with cerebral WMH. This result suggests that platelet activation plays a role in the development of cerebral WMH.

Protective effects of Capsicum fruits and their constituents on damage in TNF-α-stimulated human dermal fibroblasts.

BACKGROUND: Antioxidant and anti-inflammatory effects of natural products on skin cells have been proved to be effective in improving skin damage. Capsicum species contain capsaicinoids that have antioxidant and anti-inflammatory properties, and various subspecies are cultivated. In this study, the effects of four Capsicum fruits and major constituents on oxidative stress and inflammatory reactions were measured using human dermal fibroblasts (HDFs) to verify their effects on skin damage. RESULTS: The inhibitory effects of nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2 ) by cucumber hot pepper, red pepper (RDP), Shishito pepper (SSP), and Cheongyang pepper were determined in HDFs. RDP and SSP inhibited the production of NO, ROS, and PGE2 in tumor necrosis factor-alpha-stimulated HDFs. Additionally, SSP seeds restored tumor necrosis factor-alpha-induced increase in matrix metalloproteinase-1 and decreased procollagen I α1 (COLIA1). In high-performance liquid chromatography analysis of the capsaicinoids capsaicin (CAP) and dihydrocapsaicin (DHC), CAP was detected at a higher level than DHC in the peel and seeds of all four types of Capsicum fruits, and the total amount of capsaicinoids was the highest in SSP. CAP and DHC, which are major constituents of Capsicum fruits, also inhibited NO, ROS, and PGE2 and restored matrix metalloproteinase-1 and procollagen I α1. CONCLUSION: RDP and SSP were shown to have a significant protective effect on skin damage, including oxidative stress, inflammatory reactions, and reduction of collagens. Capsaicinoids CAP and DHC were proved as active constituents. This research may provide basic data for developing Capsicum fruits as ingredients to improve skin damage, such as inflammation and skin aging. © 2022 Society of Chemical Industry.

Reliability and Validity of the Korean Version of Disruptive Behavior Disorders Rating Scale, DSM-5 Version-Parent Form.

OBJECTIVE: Disruptive behavior disorder (DBD) adversely impacts children and adolescents. However, a comprehensive and cost-effective scale to assess DBD is lacking in Korea. Therefore, this study translated the Disruptive Behavior Disorders Rating Scale (DBDRS) into Korean and analyzed its psychometric properties. METHODS: Parents and primary caregivers of non-clinical (n=429) and clinical (n=28) children and adolescents aged 6-15 years were included in the analysis. Confirmatory factor analysis was conducted; further, concurrent validity and internal consistency were investigated using correlation analysis and Cronbach's alpha, respectively. Furthermore, discriminative capacity was estimated using receiver operating characteristic curve analysis. RESULTS: The four-factor model of K-DBDRS showed good model fit indices and factor loadings, which supported the construct validity of the scale. Strong correlations between K-DBDRS and related measurements were observed, and a robust level of Cronbach's alpha was confirmed (0.891-0.933). The discriminative capacity of the scale was good, based on the area under the curve values (0.933-0.953). CONCLUSION: This study indicated that the K-DBDRS is an appropriate screening tool for Korean children and adolescents. Thus, this scale can be applied in clinical and community settings to identify children and adolescents with disruptive behavior disorders.

Beneficial role of Boehmeria nivea in health and phytochemical constituents.

The leaf and stem extracts of Boehmeria nivea (BN) collected from three different regions in Korea were screened for their antioxidant, neuroprotective, estrogenic, insulin secretion, and α-glucosidase inhibitory activity. We also examined whether BN extracts regulate cancer cell growth, inflammatory-related gene expression, and lipid accumulation in cellular system. Leaf extracts possessed greater antioxidant, anti-proliferative in cancer cells, neuroprotective, estrogenic activity, and inhibitory effect on pro-inflammatory gene expression than stem extracts. Leaf and stem extracts inhibited lipid accumulation in three T3-L1 adipocytes but did not affect glucose-stimulated insulin secretion in INS-1 cells. We isolated and identified the phytochemical constituents in the n-butanol and ethyl acetate fractions of BN leaves by combining silica gel column chromatography with mass spectrometry and 1 H- and 13 C-NMR analysis. The active compounds (caffeic acid, isoquercitrin, p-coumaric acid, and rutin) exhibited ABTS and DPPH radical scavenging activity, which may contribute to the biological activities of BN leaf extract. An analytical method was developed to quantify marker compounds for the discrimination of BN collected from different regions. Our results support the use of this analysis method for accurate identification and quantification of marker compounds in BN for the development of functional foods. PRACTICAL APPLICATIONS: Boehmeria nivea (BN) has been used as a raw material for the textile industry or traditional herbal medicine. The current study established the biological activities and active components of BN. Our results showed that BN leaf and stem extracts exhibit antioxidant, neuroprotective, and estrogenic activity. BN leaf extract also inhibited cancer cell growth, inflammatory mediators and cytokines production, and lipid accumulation in vitro. Moreover, the bioactive compounds, such as caffeic acid, isoquercitrin, p-coumaric acid, and rutin, exert ABTS and DPPH radical scavenging activities. Therefore, BN could potentially be a promising source of bioactive phytochemicals for the development of functional foods or drugs.

Onepot-Seq: capturing single-cell transcriptomes simultaneously in a continuous medium via transient localization of mRNA.

The development of single-cell RNA-seq has broadened the spectrum for biological research by providing a high-resolution analysis of cellular heterogeneity. However, the requirement for sophisticated devices for the compartmentalization of cells has limited its widespread applicability. Here, we develop Onepot-Seq, a device-free method, that harnesses the transient localization of mRNA after lysis to capture single-cell transcriptomes simultaneously in a continuous fluid medium. In mixed-species experiments, we obtained high-quality single-cell profiles. Further, cell type-specific poly(A)-conjugated antibodies allow Onepot-Seq to effectively capture target cells in complex populations. Chemical perturbations to cells can be profiled by Onepot-Seq at single-cell resolution. Onepot-Seq should allow routine transcriptional profiling at single-cell resolution, accelerating clinical and scientific discoveries in many fields of science.

This article describes a strategy for single-cell RNA sequencing that avoids the usual imitation required by first physically compartmentalizing single cells. Based on the slow rate of mRNA diffusion relative to mRNA capture on beads, the authors devised a method that profiles single-cell mRNA among a multiple cell population, within one reaction mixture, termed 'Onepot-Seq'. This approach uses a time-constrained, transient reaction chamber that forms around each cell, with only slow diffusion of the cell contents after gentle lysis. The sparse distribution of cells and beads allows the beads to capture the profile of a single cell with minimal intercellular mRNA contamination.

Clinical outcomes of patients with multiple courses of radiosurgery for brain metastases from non-small cell lung cancer.

We investigated the long-term clinical outcomes of patients who underwent multiple courses (≥ 5) of gamma knife radiosurgery (GKRS) due to recurrent brain metastases (BM) from non-small cell lung cancer (NSCLC). Between December 2001 and July 2019, consecutive 2571 patients underwent GKRS for BM from NSCLC. Clinical and radiological outcomes were investigated in 76 patients who underwent GKRS ≥ 5 times. The median follow-up period after the diagnosis of NSCLC was 54.6 months (range 14.5-159.1 months). The median number of GKRS procedures per patient was six (range 5-15). Actuarial post-GKRS survival rates at 1, 2, 3, 4, and 5 years following initial GKRS were 88.1%, 79.5%, 65.3%, 51.4%, and 37.3%, respectively. No significant difference in overall survival was observed between patients (n = 22) with whole-brain radiotherapy (WBRT) and patients (n = 54) without WBRT (p = 0.076). The incidence of radiation-induced leukoencephalopathy was 64% and 18% in patients with and without WBRT, respectively (p < 0.0001). Multiple courses of SRS are a tolerable and effective treatment option for recurrent BM from NSCLC. Repeat SRS may be an alternative treatment option to avoid or delay WBRT.

Factors Associated with Acute Obstructive Hydrocephalus After Retrosigmoid Approach for Extra-Axial Cerebellopontine Angle Tumors.

BACKGROUND: This study aimed to identify the risk factors for acute obstructive hydrocephalus (AOHCP) after extra-axial cerebellopontine angle (CPA) tumor surgery using the retrosigmoid (RS) approach. METHODS: This retrospective study assessed 154 patients (100 vestibular schwannomas, 34 CPA meningiomas [MNGs], 9 trigeminal schwannomas, and 11 petroclival MNGs) who underwent surgical resection using the RS approach by a single surgeon between August 2010 and September 2019. AOHCP was defined as postoperative ventricular enlargement due to cerebrospinal fluid flow obstruction caused by surgery-related cerebellar injury within 1 week. The radiological characteristics of the tumors were classified, and the surgical outcomes were reviewed. We analyzed the impact of different factors on the development of AOHCP after surgery. RESULTS: AOHCP developed in 17 (11%) patients, all of whom were treated with external ventricular drain insertion. Multivariate analysis showed that CPA MNGs (odds ratio [OR], 37.98), grade of tumor extension beyond the petroclival junction (grade 1: OR, 16.42; grade 2: OR, 17.47), major fourth ventricle compression (OR, 17.77), and surgery-related hemorrhage (OR, 7.64) were associated with AOHCP. Surgery-related hemorrhage was observed in 17 (11%) patients. 9 (6%) patients underwent ventriculoperitoneal shunt surgery because of persistent HCP. CONCLUSIONS: An increased risk of AOHCP after the RS approach was observed in patients with extra-axial CPA tumors with clival extension and major fourth ventricle compression. Compulsive and meticulous hemostasis must be achieved because postoperative hemorrhage is associated with AOHCP.

Phenolic acids and flavonoids from Salvia plebeia and HPLC-UV profiling of four Salvia species.

We isolated and purified phenolic acids and flavonoids from the ethanolic extract of Salvia plebeia using silica gel and a Sephadex LH-20 column chromatography. Spectroscopy revealed the isolated compounds were caffeic acid, rosmarinic acid, hispidulin, luteolin, jaceosidin, nepitrin, homoplantaginin, 6-hydroxyluteolin 7-O-glucoside, 6-methoxynaringenin 7-O-glucoside, naasanone, and cosmosiin. Quantitative analyses, using high-performance liquid chromatography coupled with UV (HPLC-UV), revealed that the major flavonoid from S. plebeia was 6-hydroxyluteolin 7-O-glucoside (100.63 mg/g) and the most abundant phenolic acid was rosmarinic acid (47.73 mg/g). Furthermore, among four other Salvia species, S. officinalis contained the highest overall phenolic acid and flavonoid level but these were still lower than S. plebeia. These results can help assess the potential of phenolic acids and flavonoids as potent sources of pharmacological ingredients from different Salvia species extracts.

Histopathology and surgical outcome of symptomatic treatment-related changes after gamma knife radiosurgery in patients with brain metastases.

A late-onset treatment-related changes (TRCs), which represent radiographic radiation necrosis (RN), frequently occur after stereotactic radiosurgery (SRS) for brain metastases and often need surgical treatment. This study aimed to validate the true pathology and investigate clinical implication of surgically resected TRCs on advanced magnetic resonance imaging (MRI). Retrospective analyses of 86 patients who underwent surgical resection after radiosurgery of brain metastases were performed. Fifty-four patients displayed TRCs on preoperative MRI, comprising pure RN in 19 patients (TRC-RN group) and mixed viable tumor cells in 35 patients (TRC-PD group). Thirty-two patients revealed the consistent diagnosis of progressive disease in both MRI and histopathology (PD-PD group). The TRC-PD group showed larger prescription isodose volume (9.4 cm3) than the TRC-RN (4.06 cm3, p = 0.014) group and a shorter time interval from SRS to preoperative MRI diagnosis (median 4.07 months) than the PD-PD group (median 8.77 months, p = 0.004). Progression-free survival was significantly different among the three groups (p < 0.001), but not between TRC-RN and TRC-PD (post hoc test, p = 1.00), while no difference was observed in overall survival (p = 0.067). Brain metastases featured as TRCs after SRS frequently contained viable tumor cells. However, this histologic heterogeneity had a minor impact on benign local prognosis of TRCs after surgical resection.

Brite Adipocyte FGF21 Attenuates Cardiac Ischemia/Reperfusion Injury in Rat Hearts by Modulating NRF2.

Although the optimal therapy for myocardial infarction includes reperfusion to restore blood flow to the ischemic area, myocardial injury after ischemia/reperfusion usually leads to an inflammatory response, oxidative stress, and cardiomyocyte apoptosis. In this study, rat adipose-derived stem cells were differentiated into low-thermogenic beige adipocytes (LBACs) and high-thermogenic beige adipocytes (HBACs) to study the different cardioprotective effects of heterogeneous expression of brown adipocytes. We found that antioxidant and antiapoptotic factors in H9c2 cardiomyocytes were upregulated by high levels of secreted FGF21 in HBAC conditioned medium (HBAC-CM), whereas FGF21 in HBAC-CM did not affect antioxidative or antiapoptotic cell death in H9c2 cardiomyocytes with Nrf2 knockdown. These results show that NRF2 mediates antioxidative and antiapoptotic effects through the HBAC-secreted factor FGF21. Consistent with this finding, the expression of antioxidant and antiapoptotic genes was upregulated by highly secreted FGF21 after HBAC-CM treatment compared to LBAC-CM treatment in H9c2 cardiomyocytes via NRF2 activation. Furthermore, HBAC-CM significantly attenuated ischemic rat heart tissue injury via NRF2 activation. Based on these findings, we propose that HBAC-CM exerts beneficial effects in rat cardiac ischemia/reperfusion injury by modulating NRF2 and has potential as a promising therapeutic agent for myocardial infarction.

Serum Prolactin Level to Tumor Size Ratio as a Potential Parameter for Preoperative Differentiation of Prolactinomas from Hyperprolactinemia-Causing Non-functional Pituitary Adenomas.

OBJECTIVE: Preoperative diagnosis of prolactinomas is critical because dopamine agonists have been regarded as a primary treatment. However, serum prolactin level alone is suboptimal for differentiating prolactinomas from hyperprolactinemia-causing non-functioning pituitary adenomas (NFPAs). By using the tumor size, the authors tried to investigate an effective parameter for the discrimination. METHODS: We performed a retrospective review of patients who underwent trans-sphenoidal surgery for pituitary lesions in a single institute between January 2015 and May 2021. Using receiver operating curve (ROC) analyses, we compared performances of serum prolactin levels (PRL), a ratio of serum PRL levels to maximal tumor diameter (MD) (PRL/MD; PDR1), and MD squared (PRL/[MD]2; PDR2) in preoperative diagnosis of prolactinomas. RESULTS: A total of 223 patients with NFPAs (n = 175) and prolactinomas (n = 48) were included in the analysis. A moderate correlation was found between serum prolactin levels and MDs in prolactinomas (Pearson's rprl = 0.43, P = 0.002), whereas a weak correlation was observed in NFPAs (Pearson's rnfpa = 0.17, P = 0.028). Among diagnostic parameters, PDR2 exhibited the optimal diagnostic performance with the cutoff value of 0.83 [㎍/L]/mm2 (area under the curve [AUC] = 0.945), compared with the PDR1 (8.93 [㎍/L]/mm with AUC 0.938) and PRL (99.4 ㎍/L with AUC 0.910). In the external validation study, PDR2 maintained superior performance over PDR1 and PRL (accuracy of 94.8%, 91.8%, and 75.8%, respectively). CONCLUSIONS: PDR2 was a more effective indicator than prolactin alone in the preoperative differential diagnosis of prolactinomas and NFPAs, which may help select patients who need medical treatment first.

Cold-pressed oil from Citrus aurantifolia inhibits the proliferation of vascular smooth muscle cells via regulation of PI3K/MAPK signaling pathways.

Vascular occlusive disease is a chronic disease with significant morbidity and mortality. Although a variety of therapies and medications have been developed, the likelihood of disease re-emergence is high and this can be life-threatening. Based on a previous screening experiment related to vascular obstructive diseases using 34 types of essential oils, cold-pressed oil (CpO) from Citrus aurantifolia (lime) has been demonstrated to have the best effect for the inhibition of vascular smooth muscle cells (VSMCs) proliferation. The aim of the present study was to evaluate the effect of lime CpO on the pathological changes of VSMCs. To determine this, the effect of lime CpO on VSMC proliferation, a major cause of vascular disease, was investigated. To determine the safe concentration interval for toxicity of CpO during VSMC culture, a dilution of 1x10-5 was determined using Cell Counting Kit-8 assay, which was confirmed to be non-toxic using a lactate dehydrogenase assay. To examine the effect of lime CpO in cellular signaling pathways, changes in phosphorylation of both the PI3K/AKT/mTOR and extracellular signal-regulated MEK/ERK signaling pathways with serum were investigated. Furthermore, lime CpO with FBS also significantly decreased the expression levels of the cell cycle regulators cyclin D1 and proliferating cell nuclear antigen. Additionally, lime CpO with FBS significantly inhibited the sprouting of VSMCs in an ex vivo culture system. These results suggested that lime CpO inhibited the abnormal proliferation of VSMCs and can be developed as a nature-based therapeutic agent for obstructive vascular disease.