Value of 2D speckle tracking technique combined with real-time 3-dimensional echocardiography in the evaluation of the right atrial function in patients with 3-branch coronary artery disease without myocardial infarction.

To evaluate the right atrial function in patients with 3-branch coronary artery disease (TBCAD) without myocardial infarction by 2D speckle tracking echocardiography (2D-STE) combined with real-time 3-dimensional echocardiography (RT-3DE). Fifty-six patients admitted to our hospital without myocardial infarction with TBCAD were selected. We divided them into 2 groups according to the coronary angiography results: 28 patients in group B (the rate of stenosis is 50% ~< 75%); 28 patients in group C (the rate of stenosis is ≥75%); in addition, 30 healthy volunteers were screened as group A. All subjects underwent RT-3DE to obtain the right atrial volume (RAVmax, RAVmin, and RAVp), and then we calculated the right atrial passive and active ejection fraction (RAPEF, RAAEF), and maximum volume index (RAVImax). In addition, to measure the strain rates (RASRs, RASRe, RASRa) of the right atrium during systole, early diastole, and late diastole, 2D-STE was applied. Correlations between the 2D-STE parameters and the results of N-terminal pro-brain natriuretic peptide (NT-proBNP) and Gensini scores were analyzed by Pearson linear analysis. Compared with group A, RAPEF and RASRe were reduced, while RAAEF and RASRa were elevated in group B (P < .05). RAPEF, RASRs, RASRe, and RASRa were decreased compared with groups A and B, while RAVmax, RAVmin, RAVp, RAVImax, and RAAEF were increased in group C (P < .05). There was a significant correlation between 2D-STE parameters and the results of NT-proBNP and Gensini scores (P < .05). The storage, conduit, and pump functions of the right atrium are reduced in patients with 3-branch coronary artery disease without myocardial infarction; 2D-STE combined with RT-3DE is valuable in the evaluation of the right atrium in patients with coronary artery disease.

Antibody mimetics: The next generation antibody engineering, a retrospective and prospective analysis.

Antibody mimetics represent the fourth generation of antibody engineering, following polyclonal antibodies, monoclonal antibodies, and genetically engineered antibody fragments. Despite cumulative studies highlighting the advantages of antibody mimetics, including enhanced recognition properties, superior affinity, stability, penetrability, and cost-effectiveness, a comprehensive review of this evolving field is notably absent. In this study, spanning 1986-2023 and analyzing 24,318 publications, we undertake a retrospective and prospective analysis to elucidate the evolution roadmap of antibody mimetics, providing insights into the current landscape, global contributions, and future trajectories. Concurrently, our aim is to establish standardized terminology and delineate the research scope within the realm of antibody mimetics. These endeavors not only chart the trajectory and scope of antibody mimetics research but also underscore its potential to revolutionize medicine, technology, and science.

Development of indirect competitive ELISA and CLEIA for quantitative analysis of melatonin in health products.

Melatonin (MT), as a hormone regulating the rhythm of sleep, is widely used in health products. However, illicit and excessive use of MT might cause undesirable effects. Therefore, it is essential to establish highly sensitive and specific rapid methods for MT analysis in health products. In this study, we established indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and indirect competitive chemiluminescent enzyme immunoassay (ic-CLEIA) for sensitive and selective detection of MT in health products. Under optimal conditions, half-maximum inhibitory concentration (IC50 value) and limit of detection (LOD, IC10 value) for MT by ic-ELISA were 0.25 ng mL-1 and 0.03 ng mL-1 respectively, while the IC50 and LOD of ic-CLEIA were lower at 0.17 ng mL-1 and 0.03 ng mL-1 respectively. Three MT-free Chinese patent medicines were spiked with MT and the recovery rates ranged from 71.89% to 117% (ic-ELISA) and 83.66% to 107.17% (ic-CLEIA). The level of MT in six MT-containing health products was assessed in parallel using the developed methods and HPLC. Both ic-ELISA and ic-CLEIA showed good consistencies (R2 = 0.999 and 0.993, respectively) with HPLC, indicating that the two methods developed were sensitive, fast, and reliable for application in MT analysis.

ZBTB20-AS1 promoted Alzheimer's disease progression through ZBTB20/GSK-3ß/Tau pathway.

To elucidate the potential molecular mechanisms of ZBTB20-AS1 on ZBTB20 and GSK-3ß/Tau signaling pathway in the pathogenesis of Alzheimer's disease (AD), SH-SY5Y cells were obtained for in vitro experiments and AD models were constructed using ß-Amyloid 1-42. CCK8 assay was implemented for determining cell viability. Flow cytometry was used for cell apoptosis detection. Dual-luciferase reporter and RNA-RNA pull down assay was employed for elucidating molecular interactions. Immunohistochemistry, RT-qPCR and western blotting were performed for measuring gene expression. The results showed that expression of LncRNA ZBTB20-AS1 was significantly upregulated, while ZBTB20 was downregulated in SH-SY5Y-AD cells. ZBTB20 was the target gene of LncRNA ZBTB20-AS1. Overexpression of ZBTB20 or knockdown of LncRNA ZBTB20-AS1 inhibited SH-SY5Y-AD cells apoptosis and suppressed GSK3ß/Tau pathway, and knockdown of ZBTB20-AS1 increased cell viability and decreased apoptosis. In conclusion, overexpression of ZBTB20-AS1 inhibited ZBTB20 expression and promoted GSK-3ß expression and Tau phosphorylation, contributing to the development of AD.

Anti-Yo antibody-positive paraneoplastic cerebellar degeneration in a patient with possible cholangiocarcinoma: A case report and review of the literature.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD), which is rare in clinical practice, is closely related to autoimmunity. Cases positive for anti-Yo antibodies (anti-Purkinje cytoplasmic antibody 1) are the main subtype of PCD. PCD is subacute cerebellar degeneration, and while it progresses over weeks to months, its resultant deficits last much longer. Cancer patients with anti-Yo antibody-positive PCD are very rare. Most of them are breast cancer or ovarian cancer patients but also occasionally lung cancer patients. CASE SUMMARY: A 61-year-old woman presented with sudden vertigo, nausea, and vomiting for approximately 10 d. The patient's neurological examination showed torsion with downbeat nystagmus and ataxia of the right limb and trunk. Laboratory examination found that the patient's cerebrospinal fluid and serum were anti-Yo antibody-positive, positron emission tomography computed tomography showed an increased metabolic rate in the retroperitoneal lymph nodes, and the pathology of lymph node punctures in the retroperitoneum and neck suggested adenocarcinoma of the pancreaticobiliary duct, which strengthens the hypothesis of paraneoplastic origin. Intravenous immunoglobulin (IVIg) 0.4 g/kg/d for 5 d and methylprednisolone 160 mg for 3 d were initiated, which was reduced to 80 mg for 3 d and then to 40 mg for 7 d. After treatment with IVIg and a steroid, the patient's vertigo and ataxia alleviated. CONCLUSION: The patient's vertigo and ataxia alleviated after treatment, suggesting that early immunotherapeutic intervention may have certain value in stopping neurological loss.

5-Lipoxygenase as an emerging target against age-related brain disorders.

Neuroinflammation is a common feature of age-related brain disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and cerebral ischemia. 5-lipoxygenase (5-LOX), a proinflammatory enzyme, modulates inflammation by generating leukotrienes. Abnormal activation of 5-LOX and excessive production of leukotrienes have been detected in the development of age-related brain pathology. In this review, we provide an update on the current understanding of 5-LOX activation and several groups of functionally related inhibitors. In addition, the modulatory roles of 5-LOX in the pathogenesis and progression of the age-related brain disorders have been comprehensively highlighted and discussed. Inhibition of 5-LOX activation may represent a promising therapeutic strategy for AD, PD and cerebral ischemia.

Ti3+ Tuning the Ratio of Cu+ /Cu0 in the Ultrafine Cu Nanoparticles for Boosting the Hydrogenation Reaction.

Hydrogenation of diesters to diols is a vital process for chemical industry. The inexpensive Cu+ /Cu0 -based catalysts are highly active for the hydrogenation of esters, however, how to efficiently tune the ratio of Cu+ /Cu0 and stabilize the Cu+ is a great challenge. In this work, it is demonstrated that doped Ti ions can tune the ratio of Cu+ /Cu0 and stabilize the Cu+ by the TiOCu bonds in Ti-doped SiO2 supported Cu nanoparticle (Cu/Ti-SiO2 ) catalysts for the high conversion of dimethyl adipate to 1,6-hexanediol. In the synthesis of the catalysts, the Ti4+ OCu2+ bonds promote the reduction of Cu2+ to Cu+ by forming Ti3+ OV Cu+ (OV : oxygen vacancy) bonds and the amount of Ti doping can tune the ratio of Cu+ /Cu0 . In the catalytic reaction, the O vacancy activates CO in the ester by forming new Ti3+ δ OR Cu1+ δ bonds (OR : reactant oxygen), and Cu0 activates hydrogen. After the products are desorbed, the Ti3+ δ OR Cu1+ δ bonds return to the initial state of Ti3+ OV Cu+ bonds. The reversible TiOCu bonds greatly improve the activity and stability of the Cu/Ti-SiO2 catalysts. When the content of Ti is controlled at 0.4 wt%, the conversion and selectivity can reach 100% and 98.8%, respectively, and remain stable for 260 h without performance degradation.

Modulation of neuroinflammation by cysteinyl leukotriene 1 and 2 receptors: implications for cerebral ischemia and neurodegenerative diseases.

Neuroinflammation is a complex biological process and has been known to play an important role in age-related cerebrovascular and neurodegenerative disorders, such as cerebral ischemia, Alzheimer's disease, and Parkinson's disease. Cysteinyl leukotrienes (CysLTs) are potent inflammatory lipid mediators that exhibit actions mainly through activating type 1 and type 2 CysLT receptors (CysLT1 and CysLT2). Accumulating evidence shows that CysLT1 and CysLT2 are activated at different stages of pathological process in various cell types in the brain such as vascular endothelial cells, astrocytes, microglia, and neurons in response to insults. However, the precise roles and mechanisms of CysLT1 and CysLT2 in regulating the pathogenesis of cerebral ischemia, Alzheimer's disease, and Parkinson's disease are not fully understood. In this article, we focus on current advances that link activation of CysLT1 and CysLT2 to the pathological process during brain ischemia and neurodegeneration and discuss mechanisms by which CysLT1 and CysLT2 mediate inflammatory process and brain injury. Multitarget anti-inflammatory potentials of CysLT1 and CysLT2 antagonism for neuroinflammation and brain injury will also be reviewed.

Benign paroxysmal positional vertigo in spontaneous intracranial hypotension.

OBJECTIVES: To assess the prevalence and related factors of benign paroxysmal positional vertigo (BPPV) in patients with spontaneous intracranial hypotension (SIH). METHODS: We retrospectively reviewed 156 consecutive inpatients with SIH, and collected the clinical and radiological data. These patients were divided into BPPV group and non-BPPV group according to the clinical manifestation and the results of Dix-Hallpike or supine roll tests during hospitalization period. We performed a univariate analysis and a further multiple logistic regression analysis to identify the related factors of the development of BPPV in SIH patients. RESULTS: BPPV was detected in 18 patients among the total 156 SIH patients (11.54%). The univariate analysis showed a low cerebrospinal fluid (CSF) pressure (P = 0.018), a small pontomesencephalic angle (P = 0.012) and a positive venous distension sign (VDS) (P = 0.045) were associated with the presence of BPPV. But the multivariate analysis only demonstrated a low CSF pressure was related to the presence of BPPV (OR = 1.022, 95% CI: 1.001-1.043, P = 0.044). CONCLUSION: BPPV is common in SIH patients. SIH patients with low CSF pressure may be prone to develop BPPV.

Chemical composition, water vapor permeability, and mechanical properties of yuba film influenced by soymilk depth and concentration.

BACKGROUND: Yuba is a soy protein-lipid film formed during heating of soymilk. This study described yuba as an edible film by analyzing its chemical composition, water vapor permeability (WVP), and mechanical properties. Three yuba films were prepared by using different concentrations and depths of soymilk: HS (86 g kg-1 and 2.3 cm), LS (70 g kg-1 and 2.3 cm), and LD (70 g kg-1 and 3.0 cm). RESULTS: As yuba was successively skimmed, the protein, lipid, and SH content decreased, but carbohydrate and SS content increased. Though both the initial concentration and the depth of soymilk affect the properties of the films, the depth of soymilk influences WVP and tensile strength (TS) more. The WVP of the HS and LS changed the least (13-17 g mm kPa-1 m-2 day1 ), while that of the LD changed the most (13-35 g mm kPa-1 m-2 day-1 ). There were no differences (P > 0.05) in the TS between the HS and LS. LD had the greatest decrease of TS and the lowest TS among the groups. The earlier the yuba films were collected, the greater the elongation of the films was: 129% (HS), 113% (LS), and 155% (LD). CONCLUSION: The initial concentration and the depth of soymilk changed the chemical composition and structure of the yuba films. The LS yuba produced more uniform edible films with good mechanical properties. © 2017 Society of Chemical Industry.

Effects of moisture content on mechanical properties, transparency, and thermal stability of yuba film.

Yuba is the skin formed at the surface during the heating of soymilk. The 3rd, 7th, and 11th films were evaluated for properties at different RH. At 39% RH, the 11th film had the lowest moisture, while the 3rd film had the highest moisture. However, at 75% RH, reverse moisture results were obtained. The tensile strengths of the 3rd and 11th films were highest at 15% moisture, whereas the tensile strength of the 7th film was highest at 25% moisture. Elongation of the 3rd (127%) and 11th (85%) films were highest at 25% moisture. The light transmittance of the films was low and opaque at 5% moisture. The films were transparent at 23%-28% moisture, but became opaque as the moisture increased. The films at 39% RH (ΔH, 113-203J/g) had higher thermal stability than those at 87% RH (ΔH, 315-493J/g). Moisture content markedly changed the yuba film properties.

Involvement of cysteinyl leukotriene signaling in microglial morphological changes and CASP1 expression in vitro / 中国药理学与毒理学杂志

OBJECTIVE We have recently reported that cysteinyl leukotriene (CysLT) signaling plays an important role in microglial interleukin (IL)-1β secretion and subsequent neurotoxicity. The present study aimed to examine microglial morphological changes and the upstream molecular underlying IL-1βproduction in CysLT receptor agonist leukotriene D4 (LTD4)-treated BV2 microglia in vitro. METHODS Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4 (1-100 nmol·L- 1), the cell proliferation and morphology were observed. The expression level of cysteinyl aspartate-specific protease 1 (CASP1) protein was measured by Western blotin BV2 cells. In addition, BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were evaluated. RESULTS The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4, but no significant differences were observed between the control and LTD4-treated cells (P>0.05). Under basal and resting conditions, BV2 microglial cells displayed a ramified morphology. However, LTD4 at 100 nmool · L- 1 drove microglial morphological changes from a ramified towards an amoeboid shape. The expression of CASP1 protein was significantly upregulated in 100 nmool·L-1 LTD4-treated BV2 microglia (P<0.01). Furthermore, pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells (P<0.05). CONCLUSION CysLT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia, which can be inhibited by CysLT1 antagonist. These results suggest the involvement of CysLT signaling in microglial morphological changes and CASP1 expression.

CysLT2 receptor mediates lipopolysaccharide-induced microglial inflammation and consequent neurotoxicity in vitro.

Neuroinflammation induced by microglial activation plays a critical role in many neurodegenerative diseases, including Parkinson's disease (PD). Recent studies have indicated that cysteinyl leukotriene receptor 2 (CysLT2R) is involved in inflammation and brain injury after cerebral ischemia. However, the role of CysLT2R in microglial responses associated with PD remains unclear. In the present study, we determined the regulatory roles of CysLT2R in microglial inflammation and subsequent neurotoxicity in an in vitro brain inflammation model induced by the microglial activator lipopolysaccharide (LPS). We found that LPS induced phagocytosis of a murine microglial cell line (BV-2 cells) and increased production of the proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). The expression of CysLT2R protein was up-regulated and the nuclear translocation of CysLT2R was induced in LPS-activated BV-2 cells. CysLT2R selective antagonist HAMI 3379 significantly inhibited LPS-induced phagocytosis and overproduction of the cytokines in BV-2 cells. Similarly, the CysLT2R silencing by specific short hairpin RNA (shRNA) had the same effects as those of HAMI 3379, suggesting that the effect might be CysLT2R-dependent. Furthermore, the conditioned medium (CM) derived from LPS-treated BV-2 cells induced the cell death of a rat adrenal pheochromocytoma cell line (PC12). HAMI 3379 and CysLT2R shRNA attenuated neuronal death by suppressing the production of neurotoxic cytokines released from LPS-activated microglia. Collectively, these results suggest that CysLT2R mediates LPS-induced microglial inflammation and consequent neurotoxicity. CysLT2R may be a promising molecular target that modulates microglia-related neuroinflammation in neurodegenerative disorders, such as PD.

Regulation of rotenone-induced microglial activation by 5-lipoxygenase and cysteinyl leukotriene receptor 1.

The 5-lipoxygenase (5-LOX) products cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators. CysLTs mediate their biological actions through activating CysLT receptors (CysLT(1)R and CysLT(2)R). We have recently reported that 5-LOX and CysLT(1)R mediated PC12 cell injury induced by high concentrations of rotenone (0.3-10 µM), which was reduced by the selective 5-LOX inhibitor zileuton and CysLT(1)R antagonist montelukast. The purpose of this study was to examine the regulatory roles of the 5-LOX/CysLT(1)R pathway in microglial activation induced by low concentration rotenone. After mouse microglial BV2 cells were stimulated with rotenone (0.3-3 nM), phagocytosis and release of pro-inflammatory cytokine were assayed as indicators of microglial activation. We found that rotenone (1 and 3 nM) increased BV2 microglial phagocytosis and the release of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Zileuton and montelukast prevented rotenone (3 nM)-induced phagocytosis and cytokine release. Furthermore, rotenone significantly up-regulated 5-LOX expression, induced 5-LOX translocation to the nuclear envelope, and increased the production of CysLTs. These responses were inhibited by zileuton. Rotenone also increased CysLT(1)R expression and induced nuclear translocation of CysLT(1)R. In primary rat microglia, rotenone (10 nM) increased release of IL-1ß and TNF-α, whereas zileuton (0.1 µΜ) and montelukast (0.01 µΜ) significantly inhibited this response. These results indicated that 5-LOX and CysLT(1)R might be key regulators of microglial activation induced by low concentration of rotenone. Interference of 5-LOX/CysLT(1)R pathway may be an effective therapeutic strategy for microglial inflammation.