Novel SERS Signal Amplification Strategy for Ultrasensitive and Specific Detection of Spinal Cord Injury-Related miRNA.

The expression of microRNA (miRNA) changes in many diseases plays an important role in the diagnosis, treatment, and prognosis of diseases. Spinal cord injury (SCI) is a serious disease of the central nervous system, accompanied by inflammation, cell apoptosis, neuronal necrosis, axonal rupture, demyelination, and other pathological processes, resulting in impaired sensory and motor functions of patients. Studies have shown that miRNA expression has changed after SCI, and miRNAs participate in the pathophysiological process and treatment of SCI. Therefore, quantitative analysis and monitoring of the expression of miRNA were of great significance for the diagnosis and treatment of SCI. Through the SCI-related miRNA chord plot, we screened out miRNA-21-5p and miRNA-let-7a with a higher correlation. However, for traditional detection strategies, it is still a great challenge to achieve a fast, accurate, and sensitive detection of miRNA in complex biological environments. The most frequently used method for detecting miRNAs is polymerase chain reaction (PCR), but it has disadvantages such as being time-consuming and cumbersome. In this paper, a novel SERS sensor for the quantitative detection of miRNA-21-5p and miRNA-let-7a in serum and cerebrospinal fluid (CSF) was developed. The SERS probe eventually formed a sandwich-like structure of Fe3O4@hpDNA@miRNA@hpDNA@GNCs with target miRNAs, which had high specificity and stability. This SERS sensor achieved a wide range of detection from 1 fM to 1 nM and had a good linear relationship. The limits of detection (LOD) for miRNA-21-5p and miRNA-let-7a were 0.015 and 0.011 fM, respectively. This new strategy realized quantitative detection and long-term monitoring of miRNA-21-5p and miRNA-let-7a in vivo. It is expected to become a powerful biomolecule analysis tool and will provide ideas for the diagnosis and treatment of many diseases.

Association between cardiovascular risk factors and atrial fibrillation.

Background: The most prevalent sustained arrhythmia in medical practice, atrial fibrillation (AF) is closely associated with a high risk of cardiovascular disease. Nevertheless, the risk of AF associated with cardiovascular risk factors has not been well elucidated. We pooled all published studies to provide a better depiction of the relationship among cardiovascular risk factors with AF. Methods: Studies were searched in the MEDLINE, Web of Science, and EMBASE databases since initiation until January 15, 2022. Prospective cohort studies assessing the relationship a minimum of single cardiovascular risk factors to AF incidence were included if they contained adequate data for obtaining relative risks (RR) and 95% confidence intervals (CI). Random-effects models were utilized to perform independent meta-analyses on each cardiovascular risk factor. PROSPERO registry number: CRD42022310882. Results: A total of 17,098,955 individuals and 738,843 incident cases were reported for data from 101 studies included in the analysis. In all, the risk of AF was 1.39 (95% CI, 1.30-1.49) for obesity, 1.27 (95% CI, 1.22-1.32) per 5 kg/m2 for increase in body mass index, 1.19 (95% CI, 1.10-1.28) for former smokers, 1.23 (95% CI, 1.09-1.38) for current smokers, 1.31 (95% CI, 1.23-1.39) for diabetes mellitus, 1.68 (95% CI, 1.51-1.87) for hypertension, and 1.12 (95% CI, 0.95-1.32) for dyslipidemia. Interpretation: Adverse cardiovascular risk factors correlate with an increased risk of AF, yet dyslipidemia does not increase the risk of AF in the general population, potentially providing new insights for AF screening strategies among patients with these risk factors. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO identifier (CRD42022310882).

Application of Nanotechnology-Based Products in Stroke.

Stroke is a disease with high disability and high mortality in the world. Due to the existence of the blood-brain barrier (BBB), complex brain structure, and numerous neural signal pathways, the treatment methods are limited, so new drugs and new treatments need to be developed urgently. Thankfully, the advent of nanotechnology offered a new opportunity for biomedical development because of the unique properties of nanoparticles that give them the ability to traverse the BBB and accumulate in relevant regions of the brain. More importantly, nanoparticles could be modified on the surface to meet a variety of specific properties that people need. Some could be used for effective drug delivery, including tissue plasminogen activator (tPA), neuroprotective agents, genes, and cytokines; some nanoparticles were used as contrast agents and biosensors in medical imaging for further diagnosis of stroke; some were used to track target cells for prognosis of stroke; and some were used to detect pathological markers of stroke that appear at different stages. This Review looks at the application and research progress of nanoparticles in the diagnosis and treatment of stroke, hoping to bring some help to researchers.

Label-free SERS ultrasensitive and universal detection of low back pain fingerprint based on SERS substrate.

Low back pain (LBP) seriously endangers human health and quality of life, and the detection of thoracolumbar fasciitis (TLF) is vital for the prevention and treatment of LBP. Surface-enhanced Raman scattering (SERS) is considered as a powerful technique for fingerprint detection due to the inherent richness of the spectral data. In this work, a novel SERS strategy based on a three-dimensional substrate was developed for fingerprint analysis for early diagnosis of TLF. A rat TLF model was established and the model was evaluated from the immunological and behavioral perspectives. Vibrational fingerprints were obtained by SERS testing of isolated fascial tissue and were used to explore the material changes during fasciitis. SERS spectra were analyzed using principal component analysis (PCA) that allowed unambiguous distinction and monitoring of component changes during TLF. Furthermore, in order to further clarify the occurrence and development of TLF, we combined clinical samples for analysis, and investigated the inflammatory factor expression levels of CRP and SAA in TLF. Our results demonstrated that tryptophan, phenylalanine and glycogen could unambiguously distinguish TLF as confirmed by SERS analysis, a method that is capable of noninvasive characterization of and diagnosis of TLF during LBP. We have provided a new tool that may promote in-depth study of the mechanism and treatment of fasciitis.

A novel electrochemical IL-6 sensor based on Au nanoparticles-modified platinum carbon electrode.

Introduction: Interleukin-6 (IL-6) is a multifunctional polypeptide cytokine composed of two glycoprotein chains, which plays an important role in many cellular reactions, pathological processes, diagnosis and treatment of diseases and so on. The detection of IL-6 plays a promising role in the cognition of clinical diseases. Methods: 4-mercaptobenzoic acid (4-MBA) was immobilized on the gold nanoparticles modified platinum carbon (PC) electrode with the linker IL-6 antibody, and finally formed an electrochemical sensor that specifically recognized IL-6. Through the highly specific antigen-antibody reaction, the IL-6 concentration of the samples to be detected. The performance of the sensor was studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Results: The experimental results showed that the linear detection range of the sensor for IL-6 was 100 pg/mL-700 pg/mL and the detection limit was 3 pg/mL. In addition, the sensor had the advantages of high specificity, high sensitivity, high stability and reproducibility under the interference environment of bovine serum albumin (BSA), glutathione (GSH), glycine (Gly) and neuron specific enolase (NSE), which provided a prospect for specific antigen detection sensor. Discussion: The prepared electrochemical sensor successfully detected the content of IL-6 in standard and biological samples, showing excellent detection performance. No significant difference was found between the detection results of the sensor and that of ELISA. The sensor showed a very broad prospect in the application and detection of clinical samples.

Bone Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling of Degenerated Nucleus Pulposus Cells via the miR-101-3p/EIF4G2 Axis.

The etiology of lumbocrural pain is tightly concerned with intervertebral disk degeneration (IDD). Bone mesenchymal stem cell (BMSC)-based therapy bears potentials for IDD treatment. The properties of microRNA (miRNA)-modified BMSCs may be altered. This study investigated the role and mechanism of BMSCs promoting extracellular matrix (ECM) remodeling of degenerated nucleus pulposus cells (NPCs) via the miR-101-3p/EIF4G2 axis. NPCs were collected from patients with IDD and lumbar vertebral fracture (LVF). The expressions of miR-101-3p and ECM-related proteins, Collagen-I (Col-I) and Collagen-II (Col-II), were detected using the reverse transcription-quantitative polymerase chain reaction. The expressions of Col-I and Col-II, major non-collagenous component Aggrecan, and major catabolic factor Matrix metalloproteinase-13 (MMP-13) were detected using Western blotting. BMSCs were cocultured with degenerated NPCs from patients with IDD. Viability and apoptosis of NPCs were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. After the degenerated NPCs were transfected with the miR-101-3p inhibitor, the expressions of ECM-related proteins, cell viability, and apoptosis were detected. The targeting relationship between miR-101-3p and EIF4G2 was verified. Functional rescue experiments verified the effects of miR-101-3p and EIF4G2 on ECM remodeling of NPCs. Compared with the NPCs of patients with LVF, the degenerated NPCs of patients with IDD showed downregulated miR-101-3p, Col-II, and Aggrecan expressions and upregulated MMP-13 and Col-I expressions. BMSCs increased the expressions of miR-101-3p, Aggrecan, and Col-II, and decreased the expressions of MMP-13 and Col-I in degenerated NPCs. BMSCs enhanced NPC viability and repressed apoptosis. Downregulation of miR-101-3p suppressed the promoting effect of BMSCs on ECM remodeling. miR-101-3p targeted EIF4G2. Downregulation of EIF4G2 reversed the inhibiting effect of the miR-101-3p inhibitor on ECM remodeling. In conclusion, BMSCs increased the miR-101-3p expression in degenerated NPCs to target EIF4G2, thus promoting the ECM remodeling of NPCs.

Prevalence and correlates of sleep problems among Chinese prisoners.

PURPOSE: This study aimed to investigate the prevalence and correlates of sleep problems in a large prison in China. METHODS: A total of 1491 incarcerated male adults (35.44 ± 9.67 years, range 18-69) were assessed by a self-administered structured questionnaire. Sleep duration, insomnia, sleep quality, substance abuse history, gambling history, traumatic life events, posttraumatic stress disorder (PTSD) and depressive symptoms were measured. Type of offense, history of incarceration, sentence length, and duration in prison were recorded. Multivariate logistic regression was used to examine correlated factors of sleep problems. RESULTS: Overall, 17.4% (95% CI 15.6-19.5%) slept less than 6 h at night, 35.6% (95% CI 33.2-38.0%) slept 6-7 h, and 47.0% (95% CI 44.5-49.6%) slept 7 h or more. The prevalence rates were 26.2% (95% CI 24.0-28.5%) for insomnia and 45.9% (95% CI 43.4-48.4%) for poor sleep quality. Multiple models showed that older age, being divorced/widowed, poor physical health, long duration in prison, drug use before incarceration, PTSD and depression were associated with short sleep duration; while older age, poor physical health, PTSD, depression, and gambling before incarceration were associated with increased incidence of insomnia, and that being divorced/widowed, poor physical health, PTSD, depression, smoking before incarceration were related to poor sleep quality. CONCLUSIONS: These findings indicate that sleep loss, insomnia, and poor sleep quality are common in prisoners, and that sleep problems are associated with multiple psychosocial factors.

Grape Seed Proanthocyanidin Extract Ameliorates Cardiac Remodelling After Myocardial Infarction Through PI3K/AKT Pathway in Mice.

Myocardial infarction is one of the most serious fatal diseases in the world, which is due to acute occlusion of coronary arteries. Grape seed proanthocyanidin extract (GSPE) is an active compound extracted from grape seeds that has anti-oxidative, anti-inflammatory and anti-tumor pharmacological effects. Natural products are cheap, easy to obtain, widely used and effective. It has been used to treat numerous diseases, such as cancer, brain injury and diabetes complications. However, there are limited studies on its role and associated mechanisms in myocardial infarction in mice. This study showed that GSPE treatment in mice significantly reduced cardiac dysfunction and improved the pathological changes due to MI injury. In vitro, GSPE inhibited the apoptosis of H9C2 cells after hypoxia culture, resulting in the expression of Bax decreased and the expression of Bcl-2 increased. The high expression of p-PI3K and p-AKT was detected in MI model in vivo and in vitro. The use of the specific PI3K/AKT pathway inhibitor LY294002 regressed the cardio-protection of GSPE. Our results showed that GSPE could improve the cardiac dysfunction and remodeling induced by MI and inhibit cardiomyocytes apoptosis in hypoxic conditions through the PI3K/AKT signaling pathway.

Role of Maternal Nutrition in the Health Outcomes of Mothers and Their Children: A Retrospective Analysis.

BACKGROUND Low nutrition status of mothers plays an important role in increasing the prevalence of poor pregnancy outcomes. Poor pregnancy outcomes are the most common in the Guangzhou region of China. The objective of the study was to evaluate the role of maternal nutrition in the improvement of health outcomes for mothers and their children in the Guangzhou region of China. MATERIAL AND METHODS In this study, pregnancy medical records of women were analyzed. Data related to questionnaires which had been provided during hospital stays for nutritional consumption were gathered. Demographic characteristics and health outcomes of mothers and their children were recorded. Correlations of health outcomes with maternal nutrition were tested with respect to Z-scores at 95% confidence level. RESULTS Based on the health outcomes of mothers and their children, the study divided participants into 2 groups. The first group was mothers and their children with good health outcomes (live births with weighing ≥2.5 kg; the GHO group, n=130) and the second group was mothers and their children with poor health outcomes (miscarriage or premature birth with weighing less than 2.5 kg; the PHO group, n=70). These results showed positive correlation between financial status of the mother (salaried, P<0.001), maternal body mass index (P=0.001), maternal nutrition (P<0.001), maternal education (in years, P<0.001), and maternal age (P=0.004)) with health outcomes of mothers and their children. CONCLUSIONS The financial status of the mother, maternal nutrition, maternal age, and maternal education were the key determinants for predicting health outcomes of mothers and their children.

Bioequivalence of Oral Formulations of Anastrozole in Healthy Chinese Male Volunteers: A Randomized, Single-Dose, Two-Period, Two-Sequence Crossover Study.

Anastrozole is currently used as first-line treatment in locally advanced or metastatic breast cancer. A generic anastrozole tablet was developed to offer an alternative to the marketed tablet formulation. The aim of the current study was to evaluate the bioequivalence between the test and reference formulations of anastrozole in a single-dose, 2-period, 2-sequence crossover study with a 14-day washout interval. A total of 20 healthy male Chinese volunteers were enrolled and completed the study, after oral administration of a single dose of 1.0-mg test and reference formulations of anastrozole. The blood samples were collected at different times and were determined by a fully validated high-pressure liquid chromatography-tandem mass spectrometry method. The evaluated pharmacokinetic parameters, including Cmax , AUC0-t , and AUC0-∞ , were assessed for bioequivalence based on current guidelines. The observed pharmacokinetic parameters of anastrozole of the test drug were similar to those of the reference formulation. The 90% confidence intervals of test/reference ratios for Cmax , AUC0-t , and AUC0-∞ were within the bioequivalence acceptance range of 80%-125%. The results obtained from these healthy Chinese subjects in this study suggest that the test formulation of anastrozole 1.0-mg tablet is bioequivalent to the reference formulation (Arimidex 1.0-mg tablet).

Etoposide combined with ruxolitinib for refractory hemophagocytic lymphohistiocytosis during pregnancy: a case report and literature review.

Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder caused by uncontrolled inflammatory responses and the activation of T lymphocytes. This life-threatening disease, characterized by fever, cytopenia and hepatosplenomegaly, is extremely rare during pregnancy with high mortality. Despite the improvement of treatment regimen in recent years, HLH is still a great challenge for clinicians. Here, we described a 26-year-old woman who admitted to our hospital at her first pregnancy with pyrexia. Her condition continued to deteriorate after receiving broad-spectrum antimicrobials, presenting with fever, pancytopenia, hepatosplenomegaly, ferritin ≥ 500 µg/L, hemophagocytosis and low NK-cell activity. HLH was eventually diagnosed by clinical manifestation and laboratory examination results. Then the patient recovered well after treatment with etoposide combined with ruxolitinib therapy and underwent successful induced-labor operation. Additionally, we summarized similar cases from the literature to improve the management of HLH during pregnancy. In conclusion, this study highlights the challenges and difficulties in the diagnosis and management of patients with HLH during pregnancy. Moreover, this is the first case report of etoposide combined with ruxolitinib in the treatment of patients with refractory secondary HLH during pregnancy.

Osthole attenuates myocardial ischemia/reperfusion injury in rats by inhibiting apoptosis and inflammation.

This study was performed to evaluate the cardioprotective effects of osthole (OST) in a rat model of myocardial ischemia/reperfusion injury (MI/RI) and the underlying mechanism. We exposed rat hearts to left anterior descending coronary artery ligation for 30 min followed by 24 h of reperfusion. The results showed that pretreatment with OST ameliorated MI/RI as evidenced by histopathological examination. Moreover, the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay demonstrated that OST suppressed myocardial apoptosis, which may be related to an increase in the Bcl-2/Bax ratio and inhibition of caspase-3 and caspase-9 activation. Furthermore, we determined that OST ameliorated impaired mitochondrial morphology and the oxidation system; OST also attenuated levels of pro-inflammatory cytokines, including tumor necrosis factor α and interleukins 6 and 1ß. In conclusion, OST exerted a strong favorable cardioprotective effect on MI/RI, possibly by suppressing the inflammatory response and inhibiting cell apoptosis.

Retracted Article: Chrysin attenuates myocardial ischemia-reperfusion injury by inhibiting myocardial inflammation.

The aim of this study was to investigate the effects of chrysin (CH) on myocardial ischemia-reperfusion injury. Cytokines were reduced by CH in coronary artery occlusion-induced rats and also in H9C2 cells. The ST segment was also restored by CH. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that CH could alleviate myocardial injury. Results in H9C2 cells showed that CH improved heart injury in hypoxia/reoxygenation (H/R) of H9C2 cells. In addition, the expressions of the HMGB1-related inflammation pathway in rats and H9C2 cells were significantly decreased by CH. The present study shows the protective effects of CH on myocardial injury via inflammation.

Pitavastatin attenuates atherosclerosis by suppressing NF-κB signaling in a high-cholesterol diet plus balloon catheter injury rabbit model.

Atherosclerosis (AS) induced by endothelial cell (EC) dysfunction significantly contributes to the onset and development of cardiovascular disease. Pitavastatin is a member of the lipid-lowering drugs, statins that are widely used in clinics. In the current study, we evaluated the effect of pitavastatin on AS and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in abdominal aortic ECs. We induced AS in rabbits by high-cholesterol diet plus balloon catheter injury. The anti-AS effect of pitavastatin was assessed by measuring the intima-media thickness of the abdominal aorta, minimal lumen area (MLA), minimal lumen diameter (MLD), and other hemodynamic parameters. In addition, we measured the production of total cholesterol (CHOL, high density lipoproteins (HDL), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) in the rabbits. To explore the underlying mechanism of pitavastatin on atherosclerosis, we isolated abdominal aortic ECs and determined the activity of NF-κB signaling. In our model, we found that the affected animals had structural impairments of the heart and arteries: reduced left atrium diameter, right ventricular internal diameter, MLA, and MLD and increased interventricular septal thickness, left ventricular internal diameter, left ventricular posterior wall thickness, right atrium diameter, and intima-media thickness of abdominal aorta. Most of these changes were restored by administration of pitavastatin. Moreover, concentrations of plasma lipids were also attenuated by pitavastatin. At the molecular level, pitavastatin inhibited the expression of NF-κB and Bax and induced the production of IL-1ß and Bcl-2. In addition, we demonstrated that the anti-AS effect of pitavastatin depends on restoring normal function of ECs and eliminating dysfunctional ECs by inducing apoptosis.

Effects of small interfering RNA targeting TLR4 on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome with hypertension in a rat model.

We explored the effects of RNA interference-mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real-time polymerase chain reaction (qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference-mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines.

Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type.

Macrophage polarization is flexible, and involves in different signaling pathways and various transcription factors. Suppressor of cytokine signaling (SOCS) is an important inhibitor of cytokine signaling pathways and also a key physiological regulator for natural and acquired immunity systems. Following transfection of SOCS1 short hairpin (sh)RNA into mouse macrophage cells, reverse transcription­quantitative polymerase chain reaction demonstrated that the mRNA levels of Janus kinase (JAK)1 and signal transducer and activator of transcription (STAT)1 increased significantly. In addition, western blotting indicated that JAK1, STAT1 and p­STAT1 expression was significantly enhanced. Fludarabine can inhibit phosphorylation of STAT1 and SOCS1 expression. When fludarabine was added and SOCS1 shRNA was transfected, the inhibition of fludarabine was weakened, and p­STAT1 expression was upregulated. Flow cytometry detection indicated that, following the downregulation of SOCS1 expression, M1­type cells significantly increased, but the proportion of M2­type cells did not change significantly. Fludarabine can reduce the effect of SOCS1 shRNA on promoting M1­type cell polarization, and macrophages can polarize into both M1 and M2 phenotypes. Further ELISA results presented that, when downregulating SOCS1 expression, interleukin (IL)­4 and IL­10 expression was both downregulated, and tumor necrosis factor (TNF)­α and interferon (IFN)­Î³ expression was significantly upregulated. When adding fludarabine or injecting with the traditional Chinese medicine Xuebijing, IL­4 and IL­10 expression was both significantly upregulated, and TNF­α and IFN­Î³ expression was significantly downregulated. When adding fludarabine and downregulating SOCS1, IL­4, IL­10, TNF­α and IFN­Î³ expression presented no significant changes. The above results indicated that, when SOCS1 expression is downregulated, it will activate the JAK1/STAT1 pathway, and thereby promote the polarization of macrophages into M1 type. The findings are of great importance for understanding occurrence, development and treatment of various immune­related diseases.

A bioequivalence study of two memantine formulations in healthy Chinese male volunteers
.

OBJECTIVE: The aim of the current study is to evaluate the bioequivalence between the test and reference formulations of memantine in a single-dose, two-period and two-sequence crossover study with a 44-day washout interval. MATERIALS AND METHODS: A total of 20 healthy Chinese male volunteers were enrolled and completed the study, after oral administration of single doses of 10 mg test and reference formulations of memantine. The blood samples were collected at different time points and memantine concentrations were determined by a fully validated HPLC-MS/MS method. The evaluated pharmacokinetic parameters (test vs. reference) including Cmax (18 ± 3.2 vs. 17.8 ± 3.4), AUC0-t (1,188.5 ± 222.2 vs. 1,170.9 ± 135.7), and AUC0-∞ (1,353.3 ± 258.6 vs. 1,291.3 ± 136.7) values were assessed for bioequivalence based on current guidelines. RESULTS: The observed pharmacokinetic parameters of memantine test drug were similar to those of the reference formulation. The 90% confidence intervals of test/reference ratios for Cmax, AUC0-t, and AUC0-∞ were within the bioequivalence acceptance range of 80 - 125%. CONCLUSION: The results obtained from the healthy Chinese subjects in this study suggests that the test formulation of memantine 10 mg tablet is bioequivalent to the reference formulation (Ebixa®10 mg tablet).
.

Rhein attenuates inflammation through inhibition of NF-κB and NALP3 inflammasome in vivo and in vitro.

Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein. In addition, the production of proinflammatory cytokines, including IL-6, IL-1ß, and tumor necrosis factor-α, were significantly reduced in lipopolysaccharide (LPS)-induced RAW264.7 macrophages treated with rhein. Parallel to the inhibition of proinflammatory cytokines, rhein significantly reduced phosphorylation levels of NF-κB p65 and inducible nitric oxide synthase, as well as COX-2 protein expression levels. Furthermore, rhein significantly reduced NALP3 and cleaved IL-1ß expression in LPS + ATP-induced RAW264.7 macrophages. Thus, the present study demonstrates that rhein may exhibit its anti-inflammatory action via inhibition of NF-κB and NALP3 inflammasome pathways.

Soluble Egg Antigen Activates M2 Macrophages via the STAT6 and PI3K Pathways, and Schistosoma Japonicum Alternatively Activates Macrophage Polarization to Improve the Survival Rate of Septic Mice.

Sepsis is one of the most challenging health problems worldwide. Our previous study showed that chronic schistosoma japonica (SJ) infection might increase serum anti-inflammatory factors to play a protective role, thus improving the survival rate of septic mice. Further research revealed that SJ infection promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS-induced activation of M1 macrophages; up-regulated CD163, IL-10, and TGF-ß1 expression; inhibited TNF-α and iNOS expression; and blocked the effect of LPS-promoted TNF-α and iNOS expression. Furthermore, adoptive transfer of ex vivo programed M2 macrophages significantly increased the survival rate of septic mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played the same role as worm infection but had no impact on M1 macrophages. SEA reduced LPS-induced TNF-α and iNOS expression, decreased the inhibitory effect of LPS on IL-10 and TGF-ß1 expression, increased STAT6 phosphorylation, and up-regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K inhibitors were added, SEA-induced expression of CD163, IL-10, and arg1 might be reduced. Therefore, worm infection has a protective effect in septic mice in which SEA may play a key role via the STAT6 and PI3K pathways. This finding may provide a favorable solution for the treatment of sepsis, especially early cases. J. Cell. Biochem. 118: 4230-4239, 2017. © 2017 Wiley Periodicals, Inc.

Bone marrow mesenchymal stem cells inhibit dendritic cells differentiation and maturation by microRNA-23b.

Research on regulation and its mechanism of bone marrow mesenchymal stem cells (BMSCs) on dendritic cells (DCs), which is the initiating factor in immune response has applicable clinical value. Although BMSCs have a significant regulatory effect on the maturation of DCs, its molecular mechanism is still unclear. BMSCs and DCs, were co-cultured by different concentration ratios. Flow cytometry was used to detect the expression of DC markers (CD83, CD11c). Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of related genes in RNA level. Expression of the target proteins was detected with using Western blot assay. miRNA inhibitor and miRNA mimic were used to suppress and up-regulate the expression of the target gene. In this research, our results demonstrated that BMSCs notably inhibited maturation of DCs in the co-culture system of BMSCs and DCs and confirmed that this inhibition is due to overexpression of miR-23b Furthermore, this research found that miR-23b overexpression inhibited the expression of p50/p65, thus blocked the activation of the NF-κB pathway. In conclusion, BMSCs affected the activation of NF-κB pathway through miR-23b overexpression resulting in inhibition of the maturation and differentiation of DCs.