[Analysis of reproductive outcomes in the first IVF-ET cycle after laparoscopic treatment in patients with endometriosis].

Objective: To explore the effect of endometriosis (EM) on reproductive outcomes of young patient with EM after laparoscopic treatment in the first in vitro fertilization-embryo transfer (IVF-ET) cycle. Methods: The clinical data and reproductive outcomes of 394 infertile patients with EM after laparoscopic treatment (EM group) and 3 242 infertile patients caused by gamete transport disorder (control group) in the first IVF-ET cycle were collected in Chongqing Health Center for Women and Children from January 2016 to June 2021. The information included baseline characteristics, oocyte retrieval, embryo development, clinical pregnancy, miscarriage, and live birth. Propensity score matching (PSM) method was used to perform 1∶2 matching between EM group and control group. The impact of EM on reproductive outcomes was analyzed in the retrospective observational study. Results: In the initial data, compared with control group, the number of two pronucleus (2PN) zygotes (9.7±4.8 vs 9.0±4.4), the number of transferable embryos (6.2±3.6 vs 5.5±3.4) and the rate of transferable embryos (64.0% vs 60.8%) on the third day were significantly lower in EM group, and the differences were statistically significant (all P<0.05). After PSM was performed, there were 394 and 787 cases in EM group and control group, respectively. Compared with control group, the number of 2PN zygotes (9.7±4.9 vs 9.0±4.4), the 2PN fertility rate (77.1% vs 75.3%), the number of transferable embryos on the third day (6.2±3.6 vs 5.5±3.4), the transferable embryos rate on the third day (63.8% vs 60.8%) were significantly lower in EM group, and the differences were statically significant (all P<0.05). The study did not find the effect of EM on embryo implantation rate, pregnancy rate, early miscarriage rate, live birth rate and preterm birth rate (all P>0.05). Conclusions: EM might interfere with the development of oocytes and embryos. Obtaining top-quality embryos may be an effective way to improve the prognosis of patients with EM after laparoscopic treatment.

Comparative analysis and differentiation between SAPHO syndrome and spondyloarthropathies using whole-spine MRI.

AIM: To determine the imaging characteristics of SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome and seronegative spondyloarthropathies (SpAs) on whole-spine magnetic resonance imaging (WS-MRI) and evaluate the role of WS-MRI in the diagnosis and differentiation of the two diseases. MATERIALS AND METHODS: Twenty-eight patients with SAPHO and 44 with SpAs were included. All patients were symptomatic and clinically diagnosed with SAPHO or SpAs, and all underwent WS-MRI for comparison of imaging characteristics. RESULTS: The mean age of the SAPHO patients was 48.7 ± 12.7 years, while that of the SpA patients was 34.7 ± 12.3 years (p<0.001). WS-MRI showed that the frequency of cervical, thoracic, and lumbar spine involvement was 53.6% versus 52.3%, 75% versus 88.6%, and 60.7% versus 63.6%, respectively (p=0.70, 0.13, and 0.80). The frequency of sacroiliac joint involvement was 7.1% and 100% (p<0.001). Continuous spinal involvement accounted for 50% versus 43.2%, 60.7% versus 84.1%, and 39.3% versus 40.9% in the cervical, thoracic, and lumbar vertebrae, respectively (p=0.03). WS-MRI showed that bone marrow oedema of spinal anterior corner was observed in 50% versus 75% (p=0.03). Vertebral body and posterior attachment involvement accounted for 85.7% versus 93.2% and 14.3% versus 34.1% (p=0.3, 0.06). The frequency of bone erosion in mobile spine was 75% and 36.4%, respectively (p=0.02). The frequency of intervertebral disc, endplate, anterior thoracic wall, and paraspinal soft-tissue swelling was 42.9% versus 18.2%, 53.6% versus 22.7%, 85.7% versus 42.2%, and 50% versus 11.4% (p=0.02, 0.00). CONCLUSIONS: Factors differentiating the two groups at WS-MRI were bone marrow oedema of the spinal anterior corner, bone erosion, and swelling of the intervertebral disc, endplate, anterior thoracic wall, and paraspinal soft-tissue.

Incidence, risk factors, and fracture healing of atypical femoral fractures: a multicenter case-control study.

The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment. INTRODUCTION: To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing. METHODS: We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing. RESULTS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1-17 years). The use of BPs was significantly associated with AFFs (p < 0.001, odds ratio = 25.65; 95% confidence interval = 10.74-61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment. CONCLUSIONS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.

CXCR3-deficient mesenchymal stem cells fail to infiltrate into the nephritic kidney and do not ameliorate lupus symptoms in MRL. Faslpr mice.

Mesenchymal stem cell therapy is a promising candidate for the treatment of systemic lupus erythematosus (SLE). To exert their efficacy fully, mesenchymal stem cells must infiltrate efficiently into the lesion sites. Here, we examined the role of CXCR3 in mesenchymal stem cell infiltration into the kidney of MRL. Faslpr mice, which highly expressed CXCL10. The phenotypes, production of immunosuppressive mediators, and capacity to inhibit T and B cells of CXCR3-deficient mesenchymal stem cells were similar to those of wild-type mesenchymal stem cells. However, they showed less infiltration into the nephritic kidney, less conjugation with endothelial cells and weaker MMP-9 expression than did wild-type mesenchymal stem cells. Consequently, CXCR3-deficient mesenchymal stem cells did not ameliorate lupus symptoms in MRL. Faslpr mice in comparison with wild-type mesenchymal stem cells. In summary, our data suggest that upregulation of CXCR3 in mesenchymal stem cells will be a good strategy to increase their infiltration into the kidney, which will improve therapeutic outcomes in SLE.

The Natural History of Severe Acute Liver Injury.

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10x elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure. RESULTS: Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death. CONCLUSIONS: A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.

Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation.

BACKGROUND: ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. There are few detailed comparisons regarding biliary complications, infective complications and patient survival between ABO-compatible (ABO-C) and ABO-I LDLT. The aim was to compare the outcomes of ABO-I LDLT with those of ABO-C LDLT using the matched-pairs method. METHODS: Patients who underwent ABO-I LDLT procedures between 2010 and 2013 were studied. They were matched for significant variables with patients who had ABO-C LDLT (1:2 matching). RESULTS: Forty-seven ABO-I LDLT procedures were included. Ninety-four patients who had ABO-C LDLT were selected as a comparator group. The incidence of cytomegalovirus, bacterial and fungal infections during the first 3 months was similar after ABO-I LDLT and ABO-C LDLT (85 versus 76 per cent, 28 versus 37 per cent, and 13 versus 20 per cent, respectively). Antibody-mediated rejection occurred after two procedures within 2 weeks of transplantation, but liver function improved with plasma exchange in both patients. There were no differences in the rate of acute rejection and biliary complications between ABO-I and ABO-C groups (P = 0.478 and P = 0.511 respectively). Three patients who had ABO-I LDLT developed diffuse intrahepatic biliary complications and progressed to graft failure. The 1-, 2- and 3-year patient survival rates after ABO-I LDLT and ABO-C LDLT were 89 versus 87 per cent, 85 versus 83 per cent, and 85 versus 79 per cent, respectively. CONCLUSION: The short-term outcomes of ABO-I LDLT were comparable to those of ABO-C LDLT in this study. ABO-I LDLT is an effective and safe transplant option with the potential to expand the pool of live donors.

Seroepidemiology of varicella-zoster virus in Korean adolescents and adults using fluorescent antibody to membrane antigen test.

We conducted a cross-sectional seroepidemiological study in 2012-2013 to determine the seroprevalence of varicella-zoster virus (VZV) in adolescents and adults living in Korea, where varicella vaccination has been recommended universally at age 12-15 months since 2005. Residual serum samples were collected from 1196 healthy adults and adolescents aged ⩾10 years between November 2012 and March 2013. The fluorescent antibody to membrane antigen (FAMA) test and enzyme-linked immunosorbent assay (ELISA) were performed to determine the seroprevalence of VZV. The seroprevalences of VZV were compared between six age groups: 10-19, 20-29, 30-39, 40-49, 50-59, and ⩾60 years. The seroprevalence of VZV in the entire study cohort was 99·1% according to the FAMA test and 93·1% as determined by ELISA. The seroprevalences of the six age groups were as follows: 96·0%, 99·5%, 99·5%, 99·5%, 100%, and 100%, respectively, by the FAMA test, and 83·3%, 93·0%, 93·0%, 97·5%, 94·5%, and 97·5%, respectively, by ELISA. Seroprevalence increased significantly with age (P < 0·001); moreover, the seroprevalence in subjects aged 10-19 years was significantly lower than in other age groups (P < 0·001), as measured by both the FAMA test and ELISA. Thus, strategies to increase protective immunity against VZV in teenagers are necessary.

Physical characterization and in vitro skin permeation of solid lipid nanoparticles for transdermal delivery of quercetin.

OBJECTIVE: Quercetin, a phenolic compound isolated from plants, can act as an antioxidant to protect the skin from oxidative stress induced by ultraviolet rays. The aims of this work were (i) to compare the physical characterization of quercetin-loaded solid lipid nanoparticles (QSLNs) and (ii) to investigate the enhanced skin permeation of quercetin using QSLNs. METHODS: QSLNs were prepared with a certain amount lipid (palmitic acid) and the different ratio of surfactant (Tween(®) 80) by homogenization and ultrasonification method. RESULTS: QSLNs showed mono-dispersed particle size distribution in the ranges of 274.0-986.6 nm and zeta potential from -50.4 to -29.4 mV. Entrapment efficiency of QSLN was 15.2-46.2%, and their crystallinity index was low (0-18.2%). In vitro occlusion test showed QSLN-2 has the highest occlusive effect due to its smallest particle size (274.0 nm), and through these result, QSLN-2 was selected as the optimum formulation. Transmission electron microscopy (TEM) analysis further confirmed the uniform spherical shape of QSLN-2 particles. Field emission-scanning electron microscope (FE-SEM) analysis and histological observation of hairless rat skin showed that the lipid particles of QSLN-2 formed a fused lipid film and, subsequently, it hydrated the surface of the rat skin. Franz diffusion cell was used to measure in vitro skin permeation of quercetin dissolved in propylene glycol (QPG), QSLN-2 and QSLN-3. The results showed that QSLN-2 (33.5 µg cm(-2) , 21.9%) exhibited higher skin permeability than QPG (6.6 µg cm(-2) , 4.2%) and QSLN-3 (14.2 µg cm(-2) , 9.1%), which was visually confirmed by confocal laser scanning microscope (CLSM) image analysis as well. CONCLUSION: The results suggest that QSLN-2, prepared with a surfactant content of 2%, could be used as useful skin delivery system for transdermal delivery of hydrophobic antioxidants such as quercetin.

Risk factors for in-hospital acquisition of carbapenem-resistant Enterobacterales in patients with severe burns.

BACKGROUND: Although patients with severe burns are prone to severe infections with antibiotic-resistant bacteria and inevitably have some risk factors for carbapenem-resistant Enterobacterales (CRE) acquisition, risk factors for CRE infection or colonization in these patients have not been investigated. AIM: To identify the independent risk factors for CRE acquisition in patients with severe burns. METHODS: Patients admitted to the burn intensive care unit (BICU) for acute burn care were categorized based on culture results during BICU care into the CRE group and non-CRE group, which included the carbapenem-susceptible Enterobacterales (CSE) and control groups. Clinical and microbiological factors were compared between the CRE and non-CRE groups, and between the CRE and CSE groups to identify independent risk factors for in-hospital CRE acquisition. FINDINGS: Among the included 489 patients, 101 (20.7%) and 388 (79.3%) patients were classified in the CRE and non-CRE groups, respectively. The non-CRE group included 91 (18.6%) and 297 (60.7%) patients in the CSE and control groups, respectively. In multivariate analysis between the CRE and non-CRE groups, exposure to other CRE-acquired patients (P = 0.018), abbreviated burn severity index score ≥9 (P = 0.012), and mechanical ventilation (P < 0.001) were associated with CRE acquisition. In multivariate analysis between the CRE and CSE groups, exposure to other CRE-acquired patients was associated with CRE acquisition (P = 0.048). CONCLUSION: Considering the limitation of controlling the burn severity in hospitalized patients, enhanced infection control measures for preventing in-hospital CRE transmission among patients with severe burns should be emphasized.

Clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia in children with febrile neutropenia.

PURPOSE: This retrospective study was performed in order to investigate the clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia (VSB) in febrile neutropenic children in the context of the increase in incidence and antibiotic resistance of VSB. METHODS: We conducted this study among neutropenic children with underlying hematology/oncology diseases who were diagnosed with VSB at a single institution from April 2009 to June 2012. Clinical and laboratory characteristics of the children as well as antibiotic susceptibility of the causative viridans streptococci were evaluated. RESULTS: Fifty-seven episodes of VSB were diagnosed in 50 children. Severe complications occurred in four children (7.0%), and a death of one child (1.8%) was attributable to VSB. Acute myeloid leukemia was the most common underlying disease (70.2% of all cases), and 71.9% of all cases received chemotherapy including high-dose cytarabine. VSB occurred at a median of 13 days (range 8-21 days) after the beginning of chemotherapy, and fever lasted for a median of 4 days (range 1-21 days). The C-reactive protein level significantly increased within a week after the occurrence of VSB (p < 0.001) and the maximum C-reactive protein level showed a positive correlation with fever duration (r = 0.362, p = 0.007). Second blood cultures were done before the use of glycopeptides in 33 children, and negative results were observed in 30 children (90.9%). Susceptibilities to cefotaxime, cefepime, and vancomycin were 58.9, 69.1, and 100%, respectively. CONCLUSIONS: Severe complications of VSB in neutropenic febrile children were rare. We suggest glycopeptide use according to the results of blood culture and antibiotic susceptibility tests based on the susceptibility to cefepime and the microbiologic response to empirical antibiotic treatment not including glycopeptides in this study.

Synovial fluid CD34⁻ CD44⁺ CD90⁺ mesenchymal stem cell levels are associated with the severity of primary knee osteoarthritis.

To the best of our knowledge, no reports have directly compared synovial fluid (SF)- and synovial membrane (SM)-derived mesenchymal stem cells (MSCs) from primary knee osteoarthritis patients in terms of MSC proportion, either immediately after isolation or during culture. Any possible correlation between SM- and SF-MSC purity and osteoarthritis severity, also remains unclear. We therefore assessed quantitative and phenotypic differences in MSCs isolated from SF and SM. We also evaluated the correlation between sample MSC purity, and disease severity, in patients with osteoarthritis. The main result of the current study was that the mean SF-MSC proportion at passage 0 was negatively correlated with Kellgren-Lawrence (KL) grade (r = -0.565, P = 0.002). In addition, KL grade was a only significant independent negative predictor of SF-MSC proportion at passage 0 (ß = -0.356, P = 0.039). Conclusively, the proportion of SF-MSCs in fresh samples, evaluated at the single cell level, was inversely correlated with osteoarthritis severity.

An update on the status of COVID-19: a comprehensive review.

The last two decades have witnessed two large-scale pandemics caused by coronaviruses, including severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). At the end of 2019, another novel coronavirus, designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hit Wuhan, a city in the center of China, and subsequently spread rapidly to the whole world. Latest reports revealed that more than 800 thousand people in over 200 countries are involved in the epidemic disease by SARS-CoV-2. Due to the high mortality rate and the lack of optimum therapeutics, it is crucial to understand the biological characteristics of the virus and its possible pathogenesis to respond to the SARS-CoV-2. Rapid diagnostics and effective therapeutics are also important interventions for the management of infection control. However, the rapid evolution of SARS-CoV-2 exerted tremendous challenges on its diagnostics and therapeutics. Therefore, there is an urgent need to summarize the existing research results to guide decision-making on the prioritization of resources for research and development. In this review, we focus on our current understanding of epidemiology, pathogenesis, diagnostics and therapeutics of coronavirus disease 2019 (COVID-19).

Glutathione peroxidase 1 deficiency attenuates concanavalin A-induced hepatic injury by modulation of T-cell activation.

Concanavalin A (Con A)-induced hepatitis model is well-established experimental T cell-mediated liver disease. Reactive oxygen species (ROS) is associated with T-cell activation and proliferation, but continued ROS exposure induces T-cell hyporesponsiveness. Because glutathione peroxidase 1 (Gpx1) is an antioxidant enzyme and is involved in T-cell development, we investigated the role of Gpx1 during Con A-induced liver injury in Gpx1 knockout (KO) mice. Male wild-type (WT) mice and Gpx1 KO mice were intravenously injected with Con A (10 mg/kg), and then killed after 8 h after Con A injection. Serum levels of aspartate transaminase and alanine transaminase were measured to assess hepatic injury. To identify that Gpx1 affects T cell-mediated inflammation, we pretreated Gpx1 inhibitor to Human Jurkat T cells then treated Con A. Con A-induced massive liver damage in WT mice but its damage was attenuated in Gpx1 KO mice. Con A-induced Th1 cytokines such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL)-2 were also decreased in the liver and spleen of Gpx1 KO mice compared with WT mice. In Jurkat T cells, Con A-induced mRNA levels of IL-2, IFN-γ and TNF-α were downregulated by pretreatment of Gpx inhibitor, mercaptosuccinic acid. We also observed that Gpx1 KO mice showed increasing oxidative stress in the liver and spleen compared with WT mice. These results suggest that Gpx1 deficiency attenuates Con A-induced liver injury by induction of T-cell hyporesponsiveness through chronic ROS exposure.

MDR-1 gene expression is a minor factor in determining the multidrug resistance phenotype of MCF7/ADR and KB-V1 cells.

The relevance of MDR-1 gene expression to the multidrug resistance phenotype was investigated. Drug-resistant cells, KB-V1 and MCF7/ADR, constantly expressed mRNA of the MDR-1 gene and were more resistant to vinblastine and adriamycin than drug-sensitive cells, KB-3-1 and MCF7. The drug efflux rate of KB-V1 was the same as KB-3-1 although the MDR-1 gene was expressed in only the resistant cell. The higher intracellular drug concentration of KB-3-1 than KB-V1 was due to the large drug influx. In the case of MCF7 and MCF7/ADR, the influx and efflux of the drug had nearly the same pattern and drug efflux was not affected by verapamil. The amount of ATP, cofactor of drug pumping activity of P-glycoprotein, was not changed by the resistance. These observations suggested that drug efflux mediated by MDR-1 gene expression was not a major determining factor of drug resistance in the present cell systems, and that the drug resistance could be derived from the change in drug uptake and other mechanisms.

Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus.

We investigated the mechanism of the immunomodulatory action of polysaccharide (ASP) isolated from a cell culture of Acanthopanax senticosus. ASP was found to directly increase the proliferation and differentiation of B cells, and the cytokine production of macrophage, but not the proliferation and cytokine production of T cells. Since ASP cannot penetrate the cell membrane due to its large molecular mass, such cellular activation may be caused by the surface binding of ASP to receptors expressed on B cells and macrophages. The possibility that TLRs, which are known to be involved in immune-related responses, may be the receptor(s) of ASP was investigated. The immunomodulating activities of ASP on the B cells and macrophages of C3H/HeJ mice, expressing a defective toll-like receptor (TLR)-4, were decreased versus the corresponding cells from C3H/HeN mice. In addition, the activities of ASP on B cells and macrophages were significantly reduced by treating the cells with antibodies to TLR4 and TLR2 prior to ASP, suggesting that both of them are the possible receptors of ASP. The ligation of TLRs induced by ASP was able to activate mitogen-activated protein kinases (MAPKs), such as Erk1/2, p38 and JNK, and the transcription factor NF-kappaB. Although ASP was shown to activate the TLR signaling cascades in the same manner as lipopolysaccharide (LPS), these two could be differentiated by the finding that polymyxin B (PMB), a specific inhibitor of LPS, did not significantly affect the activities of ASP on B cells and macrophages. Taken together, our results demonstrate that ASP, isolated from a cell culture of A. senticosus, activates B cells and macrophages by interacting with TLRs and leading to the subsequent activation of mitogen-activated protein kinases and NF-kappaB.

Activation of mitogen-activated protein kinase pathways by angelan in murine macrophages.

In our previous studies, we showed that angelan, a polysaccharide purified from Angelica gigas Nakai, specifically activated macrophages to induce cytokines including inducible nitric oxide synthase (iNOS) which has strong anti-tumor activities [Immunopharmacology, 1999; 43: 1.]. In the present study, we investigated the intracellular signal transduction pathways involved in the angelan-induced iNOS synthesis by murine macrophages. Protein tyrosine phosphorylation was induced within 5 min by angelan, and the blocking of protein tyrosine kinases (PTKs) inhibited down-stream pathways leading to iNOS production in response to angelan. Treament of RAW 264.7 cells with angelan resulted in significant activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38, while stress-activated protein kinase/c-Jun NH2 terminal kinase (SAPK/JNK) was not activated by angelan. The specific p38 inhibitor SB203580 abrogated the angelan-induced iNOS synthesis, whereas the selective mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD98059 did not affect the iNOS induction. In conclusion, we demonstrate that PTK and p38 MAPK activation are required to transduce signals leading to iNOS expression in angelan-stimulated murine macrophages.

Characterization of B cell membrane receptors of polysaccharide isolated from the root of Acanthopanax koreanum.

We investigated the immunomodulatory activity of polysaccharide isolated from the root of Acanthopanax koreanum (AK) at the cellular level. AK directly increased B cell proliferation and antibody production, but did not affect the expression of IL-2, IFN-gamma or IL-4 by T cells, or T cell proliferation in vitro. Since AK cannot penetrate cells due to its large molecular mass, B cell activation may be caused by the surface binding of AK to B cell-specific receptors. The role of TLR4 as an AK receptor was shown by the fact that AK activity in B cells from C3H/HeJ mice, which are known to have a defective Toll-like receptor (TLR)-4, was found to be reduced compared with that in control cells from C3H/HeN mice. AK activity was also reduced by antibodies blocking TLR2, TLR4, CD19 or CD79b, but not by an antibody blocking CD38, which suggests AK receptor profiling in B cells. Two main differences between AK and lipopolysaccharide (LPS) were observed. First, LPS activity was inhibited by antibodies to either TLR2 or TLR4, but not by antibodies to CD19, CD79b or CD38. Another was that LPS-induced B cell proliferation was inhibited by polymyxin B (PMB), a specific inhibitor of LPS, whereas AK activity was not affected. Taken together, our results demonstrate that AK directly activates B cells, but not T cells, and suggest that AK has a broader receptor profile than LPS in B cells.

Polysaccharide isolated from the radix of Platycodon grandiflorum selectively activates B cells and macrophages but not T cells.

Many polysaccharides isolated from plants are considered to be biological response modifiers and have been shown to enhance various immune responses in vivo and in vitro. Here, we demonstrate that polysaccharide isolated from the radix of Platycodon grandiflorum (PG) has a unique mode of immunostimulation with regard to its cell-type specificity. PG was found to markedly increase polyclonal IgM antibody production and the proliferation of B cells, and to activate iNOS transcription and NO production in macrophages. Moreover, the intraperitoneal administration of PG in mice resulted in increased IgM antibody production in B cells, which were immunized by using T-dependent antigen sheep red blood cells (sRBCs). However, PG did not affect the proliferation of T cells, the IL-2 expression of Th1 cells, or the IL-4 expression of Th2 cells. Although PG and lipopolysaccharide (LPS) had a similar mode of action in B cells and macrophages, they were differentiated by the fact that PG-induced cellular activation was not inhibited by polymyxin B, a specific inhibitor of LPS. Anti-CD19 or anti-CD79b antibody blocked B cell proliferation and anti-CD14 or anti-CD 11b antibody decreased macrophage NO production, indicating the possible cellular binding sites of PG. Our results demonstrate that PG is a specific activator of B cells and macrophages but not of T cells, and suggest that PG is quite distinct from other well-known immunostimulants, such as lentinan and schizophyllan, which mainly act upon macrophages and T cells.