Evaluation of inhibitory effect of tumor vaccine in colon carcinoma model mice / 中国生物制品学杂志

Objective@#To evaluate the inhibitory effect of tumor vaccines in colon carcinoma model mice.@*Methods@# Mouse bone marrow⁃derived dendritic cells（BMDCs）were stimulated by using CpG β⁃glucan nanoparticles（CNP）in vitro. The BMDCs were divided into PBS group，NP group（without CpG nanoparticles），Lysate group（MC38 cell lysate）and CpG group（CpG1826），which were determined for the expression of marker molecules on the surface by flow cytometry and for the contents of interleukin⁃6（IL⁃6）and IL⁃12p40 in the culture supernatant by ELISA. The tumor lysate nano⁃vaccine was pre⁃ pared by mixing 50 mg／mL tumor lysate（MC38 cell lysate）with 200 mg／mL CNP in a volume ratio of 1∶1，with which mice were subcutaneously immunized as Vaccine group. Vaccine group，PBS group，CNP group and Lysate group were im⁃ munized once a week，for three times in total. Mice were subcutaneously inoculated with MC38 cells，2 × 105 cells for each， in the right lower limb 1 h after the last immunization，and measured for tumor volume once every three days to plot the tumor growth curve. The ratios of CD3+ CD4+ T and CD3+ CD8+ T cells in the blood were analyzed by flow cytometry and the levels of tumor necrosis factor⁃α（TNF⁃α）and interferon γ（IFNγ）in the blood and spleen of mice were determined by ELISA.@*Results@# CNP effectively increased the expression of CD11c+ CD80+，CD11c+ CD86+，CD11c+ MHC⁃Ⅱ+ and the secretion of IL⁃6 and IL⁃12p40 in BMDCs in vitro，which were significantly higher than those in other 4 groups（t = 4. 3 ~ 46. 2，each P < 0. 05）. Compared with that of the other three groups，the tumor volume of mice in Vaccine group decreased significantly（t =2.6~3.4，eachP <0. 05）；TherewasnosignificantdifferenceinCD3+ CD8+ TandCD3+ CD8+ Tcellratios（t = 0.5~ 1. 9，each P > 0. 05）；The content of IFNγ in blood increased significantly（t = 3. 8 ~ 4. 6，P < 0. 05），while thatof TNF⁃α showed no significant difference（t = 0. 4 ~ 2. 0，each P > 0. 05）；However，the contents of IFN γ and TNF⁃α in spleen increased significantly（t = 6. 3 ~ 13. 0，each P < 0. 001）.@*Conclusion@#The prepared nano⁃vaccine of tumor lysate improvedtheimmune level in mice and effectively inhibited the growth of colon carcinoma.

Research progress of yeast microcapsules as oral drug delivery carrier / 中国药房

As a natural drug delivery carrier with rough and porous surface and hollow core， yeast microcapsules have good safety， high targeting and high stability， and have excellent application prospects in oral drug delivery systems. Yeast cells can be treated and washed with acid-base and organic solvents to obtain loose and porous yeast microcapsules. Yeast microcapsules can encapsulate drugs through electrostatic interactions， passive diffusion， hydrophobic interaction and other methods. The surface of yeast microcapsules is mainly composed of β-glucan， which can maintain stability in the gastrointestinal environment； it can be recognized by the surface-related receptors of immune cells， thus activating the immune response， and can be transported to the lesion site with the movement of lymphocytes after being ingested. Yeast microcapsules are safe and very suitable for delivering vaccines， anti-inflammatory drugs， and anti-tumor drugs. They can not only achieve oral delivery of the aforementioned drugs， but also enhance drug efficacy and improve drug targeting. In the future， more research on systemic transport mechanisms or the development of more efficient combination drug delivery systems can be carried out to fully exhibit the clinical value of yeast microcapsules.

Clinical value of 1, 3-β-D glucan and mannan IgM/IgG antibodies in the early diagnosis of invasive candidiasis / 中华微生物学和免疫学杂志

Objective:To evaluate the diagnostic value of 1, 3-β-D glucan (BDG), mannan IgM antibody (Mn-IgM) and mannan IgG antibody (Mn-IgG) in invasive candidiasis and to compare the differences in the diagnostic capability of serological markers used alone or in combination.Methods:Serum samples of 126 patients with invasive candidiasis and 104 healthy people who took physical examination during the same period were collected. BDG was detected by dynamic chromogenic method, and Mn-IgM and Mn-IgG were detected by ELISA. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, coincidence rate and Kappa value of the three serological markers used alone or in combination in the diagnosis of invasive candidiasis were analyzed and compared. The receiver operating characteristic (ROC) curves were drawn and the areas under the curves (AUCs) were calculated.Results:The levels of BDG, Mn-IgM and Mn-IgG in patients with invasive candidiasis were significantly higher than those in healthy people ( P<0.01). The sensitivity, specificity, Kappa value and AUC of BDG were 48.41%, 92.31%, 0.389 and 0.842. The sensitivity, specificity, Kappa value and AUC of Mn-IgM were 64.29%, 91.35%, 0.540 and 0.829. The sensitivity, specificity, Kappa value and AUC of Mn-IgG were 27.78%, 95.19%, 0.214 and 0.737. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM were 76.19%, 88.46%, 0.637 and 0.921. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgG were 59.52%, 91.35%, 0.491 and 0.856. The sensitivity, specificity, Kappa value and AUC of Mn-IgM+ Mn-IgG were 69.84%, 90.38%, 0.588 and 0.891. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM+ Mn-IgG were 80.16%, 88.46%, 0.679 and 0.922. Conclusions:The sensitivity of Mn-IgM was higher than that of BDG and Mn-IgG in the diagnosis of invasive candidiasis. When the serological biomarkers were used in combination, BDG+ Mn-IgM and BDG+ Mn-IgM+ Mn-IgG had relatively high Kappa value and AUC, showing high accuracy. The clinical diagnostic value of multiple serological biomarkers used in combination was significantly higher than that of any serological biomarkers used alone. Early combined detection and continuous monitoring of multiple serological biomarkers in patients with high risk of invasive candidiasis could be used clinically to adjust antifungal treatment strategies timely.

Effects of CEACAM1 in oral keratinocytes on HO-1 expression induced by Candida β-glucan particles

Abstract Objective Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a member of the carcinoembryonic antigen family. Although its expression has been found in chronic oral inflammatory epithelium, this study aimed to know whether CEACAM1 in oral keratinocytes participates in host immune response against Candida albicans . Methodology We investigated CEACAM1 expression in oral keratinocytes induced by C. albicans as well as by Candida cell wall component β-glucan particles (β-GPs). Furthermore, the effects of CEACAM1 on β-GPs-induced heme oxygenase-1 (HO-1) expression and its related signals were examined. Results Fluorescence staining showed CEACAM1 expression in oral keratinocytes (RT7) cells, whereas quantitative reverse transcription (RT)-PCR indicated that both live and heat-killed C. albicans increased CEACAM1 mRNA expression in RT7 cells. Examinations using quantitative RT-PCR and western blotting indicated that CEACAM1 expression was also increased by β-GPs derived from C. albicans . Specific siRNA for CEACAM1 decreased HO-1 expression induced by β-GPs from C. albicans as well as the budding yeast microorganism Saccharomyces cerevisiae . Moreover, knockdown of CEACAM1 decreased β-GPs-induced ROS activity in the early phase and translocation of Nrf2 into the nucleus. Conclusion CEACAM1 in oral keratinocytes may have a critical role in regulation of HO-1 for host immune defense during Candida infection.

Expression of anti-fungal peptide, β-defensin 118 in oral fibroblasts induced by C. albicans β-glucan-containing particles

Abstract Objective: Although oral fibroblasts are thought to have the potential to enhance host defenses against Candida albicans , it is unknown whether they are able to recognize Candida cell components to increase the expression of antifungal peptides, such as defensin factors, against Candida infection. Methodology: We performed expression profiles of defensin genes induced by heat-killed C. albicans in oral immortalized fibroblasts (GT1) using cDNA microarray analysis. From those results, quantitative RT-PCR was used to examine the effects of Candida β-glucan-containing particles (β-GPs) on β-Defensin 118 (DEFB 118) expression in oral mucosal cells. Furthermore, the antifungal activities of recombinant DEFB 118 against C. albicans and C. glabrata were investigated using fungicidal assays. Results: Microarray analysis showed that DEFB118, β-Defensin 129 (DEFB129), and α-Defensin 1 (DEFA1) genes were induced by heat-killed C. albicans and that their mRNA expressions were also significantly increased by live as well as heat-killed C. albicans . Next, we focused on DEFB118, and found that GT1, primary fibroblasts, and RT7 (oral immortalized keratinocytes) constitutively expressed DEFB118 mRNA expression in RT-PCR. Furthermore, C. albicans β-GPs significantly increased the expression of DEFB118 mRNA in GT1 and primary fibroblasts. Although DEFB118 mRNA expression in RT7 was significantly induced by both live and heat-killed C. albicans, C. albicans β-GPs failed to have an effect on that expression. Finally, recombinant DEFB118 significantly decreased the survival of both strains of C. albicans in a dose-dependent manner, whereas no effects were seen for both C. glabrata strains. Conclusion: DEFB118, induced by C. albicans β-GPs from oral fibroblasts, may play an important role in oral immune responses against C. albicans infection.

β -Glucan Improves Protective Qi Status in Adults with Protective Qi Deficiency-A Randomized, Placebo-Controlled, and Double-Blinded Trial / 中国结合医学杂志

OBJECTIVE@#To test the hypothesis that β -glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against "external pernicious influences".@*METHODS@#A total of 138 participants with PQi deficiency (PQD) were randomized to receive β -glucan (200 mg daily) or placebo for 12 weeks. Participants' PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants' immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS).@*RESULTS@#PQi status was not significantly different between the β -glucan and placebo treatment groups at baseline but improved significantly in the β -glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1-5), risk score (scale: 0-1), and proportion of PQD participants (%) at finish line was 0.49 (0.35-0.62), 0.48 (0.35-0.61), and 0.36 (0.25-0.47), respectively. Additionally, β -glucan improved URTI symptom (scale: 1-9) and PROMIS physical (scale: 16.2-67.7) and mental (scale: 21.2-67.6) scores by a magnitude (95% CI) of 1.0 (0.21-1.86), 5.7 (2.33-9.07), and 3.0 (20.37-6.37), respectively, over placebo.@*CONCLUSIONS@#β -glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as β -glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974).

Clinical features of Pneumocystis jirovecii pneumonia / 中华检验医学杂志

Objective:The clinical features, laboratory indices, and imaging data of patients with Pneumocystis jirovecii pneumonia (PJP) were described and analyzed, aiming to provide helpful information for the diagnosis and treatment of PJP. Methods:A retrospective study were conducted with data from 154 PJP patients who visited China-Japan Friendship Hospital from May 2017 to August 2020. Their clinical characteristics, laboratory and imaging data, and clinical outcomes were collected for analysis. The patients were further divided into the death group (51 cases) and the survival group(103 cases). The differences between the groups were compared by using t-test, nonparametric test, and chi-square test. Results:Of the 154 PJP patients, there were 89 males and 65 females, with a mean age of (53.7±14.8) years. Among them, 85.7% (132/154) were on immunosuppressive/glucocorticoids agents within the past month. Besides, 27.9% (43/154) and 33.1% (51/154) had kidney diseases and connective tissue diseases, respectively. The major clinical manifestations in these patients involved fever 82.9% (126/154), cough 59.7% (92/154), and dyspnea 52.6% (81/154). For the laboratory data, the lactate dehydrogenase (LDH) was 561.0 (434.3, 749.0) IU/L and the value increased in 91.3% (95/104) of the patients. The CD4+T-cell lymphocytes in 88.0% (95/108) and 57.4% (62/108) of patients were lower than 400/μl and 200/μl, respectively. Furthermore, (1, 3)-β-D glucan (BG) increased in 74.4% (67/90) of PJP patients (≥100.0 ng/L). For the imaging results, chest computed tomography (CT) showed diffuse ground-glass shadows/grid shadows in 90% (117/130) patients. Compared with the survival group, higher LDH [690.5 (528.8, 932.3) IU/L vs 502.5 (381.8, 657.0) IU/L, Z=-3.375, P=0.001], white blood cell count (WBC) [9.8 (5.8, 12.6) ×10 9/L vs 7.3 (5.0, 10.1) ×10 9/L, Z=-2.392, P=0.017], and age [(69.8±14.5) years vs (50.6±14.0) years, t=-3.756, P=0.001] were found in the death group. Lower lymphocyte ratio [5.3 (3.2, 9.3) % vs 9.6 (5.6, 17.2) %, Z=?3.262, P=0.001] and oxygen partial pressure (PaO 2) levels [(73.2±20.5) mmHg vs (64.8±17.7) mmHg (1 mmHg=0.133 kPa), t=2.345, P=0.021] were also observed in the death group. Furthermore, in the death group, the bacterial and fungal infection rate was higher than the rates in the survival group [55.1% (27/51) vs 21.5% (22/103), χ 2=15.372, P=0.001]. Conclusions:Long-term use of immunosuppressive agents or glucocorticoids predispose to PJP. CD4+T-lymphocytes, LDH, and BG might be used as important auxiliary examinations for PJP patients. Age, LDH, WBC, lymphocyte ratio, PaO 2 and possible combinations with bacterial or fungal infections are more closely related to the prognostic of PJP patients.

What is the effectiveness of beta-glucan for treatment of acute otitis media? / Qual é a eficácia do beta-glucano no tratamento da otite média aguda?

Abstract Introduction: As a supplement, beta-glucan has various therapeutic healing effects generated by the immune cells. It has been scientifically approved and proven to be a biological defense modifier. The aim of this study was to investigate the effects of beta-glucan on treatments administered in an acute otitis media model Objectives: This study investigated the effect of beta-glucan on the treatment of acute otitis media in an acute otitis media -induced animal model. Efficacy was evaluated both immunologically and histologically. Methods: The study sample comprised 35 adult rats, randomly separated into 5 groups of 7: Group 1 (control), Group 2 (acute otitis media, no treatment), Group 3 (acute otitis media + antibiotic), Group 4 (acute otitis media + beta-glucan) and Group 5 (acute otitis media + beta-glucan + antibiotic). Analyses were made of the histopathology and immunology examination results in respect of thickening of the tympanic membrane, epithelium damage, inflammation, and sclerosis. In all groups the serum levels of TNF-α, IL-4, IL-6 and IL-1β were evaluated. Results: All serum cytokine levels were significantly lower in the beta-glucan and antibiotictreated groups compared to the acute otitis media Group. Significant differences in tympanic membrane thickness, inflammation, epithelium damage, and sclerosis values were observed between the acute otitis media + antibiotic and acute otitis media + beta-glucan Groups. According to these parameters, the values in aute otitis media + antibiotic + beta-glucan Group were markedly lower than those of the other groups. There was a significant difference in the acute otitis media + antibiotic + beta-glucan Groups compared to acute otitis media Group (p < 0.001). Conclusions: Both antibiotic and beta-glucan treatment reduced acute otitis media signs of inflammations in an acute otitis media-induced rat model, decreasing histological damage and cytokine levels. Co-administration of antibiotic and beta-glucan led to a significant reduction in tympanic membrane thickness, inflammation, and epithelium damage. Antibiotic + beta-glucan treatment resulted in a greater decrease in tympanic membrane thickness, inflammation, and epithelium damage than in the other groups. From these results, it can be suggested that beta-glucan, in combination with antibiotics may provide an alternative for the treatment of acute otitis media.

Resumo Introdução: Como suplemento, o beta-glucano apresenta vários efeitos terapêuticos gerados pelas células imunológicas. Cientificamente aprovado, mostrou ser um modificador de defesa biológica. Objetivo: Investigar os efeitos do beta-glucano nos tratamentos administrados em um modelo de otite média aguda induzida em um modeloanimal. A eficácia foi avaliada imunológica e histologicamente. Método: A amostra do estudo foi composta por 35 ratos adultos, divididos aleatoriamente em 5 grupos de 7: grupo 1 (controle), grupo 2 (otite média aguda, sem tratamento), grupo 3 (otite média aguda + antibiótico), grupo 4 (otite média aguda + beta-glucano) e grupo 5 (otite média aguda + beta-glucano + antibiótico). Foram feitas análises dos resultados dos exames histopatológicos e imunológicos em relação ao espessamento da membrana timpânica, dano ao epitélio, inflamação e esclerose. Os níveis séricos de TNF-α, IL-4, IL-6 e IL-β foram avaliados em todos os grupos. Resultados: Todos os níveis séricos de citocinas foram significativamente mais baixos nos grupos tratados com beta-glucano e antibióticos em comparação com o grupo otite média aguda. Diferenças significativas na espessura da membrana timpânica, inflamação, dano do epitélio e esclerose foram observadas entre os grupos otite média aguda + antibiótico e otite média aguda + beta-glucano. De acordo com esses parâmetros, os valores no grupo otite média aguda + antibiótico + beta-glucano foram acentuadamente inferiores aos dos demais grupos. Houve uma diferença significante no grupo otite média aguda + antibiótico + beta-glucano em comparação ao grupo otite média aguda (p < 0,001). Conclusão: Ambos os tratamentos com antibiótico e com beta-glucano reduziram os sinais de inflamação da otite média aguda em um modelo de rato com otite média aguda induzida, diminuíram os danos histológicos e os níveis de citocinas. A administração concomitante de antibiótico e beta-glucano levou a uma redução significativa na espessura da membrana timpânica, inflamação e danos ao epitélio. O tratamento com antibióticos + beta-glucano resultou em maior diminuição na espessura da membrana timpânica, inflamação e danos no epitélio do que nos outros grupos. A partir desses resultados, pode-se sugerir que o beta-glucano, em combinação com antibióticos, pode fornecer uma opção para o tratamento da otite média aguda.

Proof-of-Concept and Feasibility Study to Evaluate the Effect of β-Glucan on Protective Qi Deficiency in Adults / 中国结合医学杂志

OBJECTIVE@#To preliminarily explore the potential effect of β-glucan on Chinese medicine (CM) concept protective qi deficiency (PQD), and the methodology for future definitive studies.@*METHODS@#To have a standardized assessment of PQD, a list of 13 potentially PQD-relevant parameters were firstly created, each with defined quantitative or categorial scales. Using the data from 37 participants with (21 cases) or without (16 cases) PQD, multivariate logistic modeling was conducted to create a preliminary diagnostic PQD risk score. Subsequently, 21 participants diagnosed with PQD were treated with β-glucan in a dose of 200 mg/day for 8 weeks. Data were collected for trial acceptability measures (rate of recruitment, withdrawal, and compliance), and the participants were assessed for PQD status at baseline and every 2 weeks thereafter.@*RESULTS@#The preliminary logistic model consisted of 3 parameters (low voice and apathy, aversion to wind and cold, and Cun pulse). The resulting risk score demonstrated a degree of PQD-predicting accuracy that, as evaluated by statistical (discrimination and classification) methods, was higher than those obtained from any of the individual candidate parameters. The 21 PQD participants treated with β-glucan demonstrated good receptibility and a time-dependent improvement in PQD status as evidenced by the decrease of PQD participant to 9.5% at the end of study.@*CONCLUSIONS@#This study demonstrated the effect of proof-of-concept of β-glucan on improving PQD and the proof-of-concept of a multivariate-model-derived diagnostic PQD risk score. It also indicated feasibility for future definitive studies. Studies like this embody an innovative approach that uses therapies derived from the mainstream biomedicine to enrich therapeutics guided by CM principle. (Trial registration No. NCT03829228).

Effect of berberine hydrochloride on cell wall integrity of Candida albicans hypha / 中国中药杂志

The aim of this paper was to investigate the effect of berberine hydrochloride on the cell wall integrity of Candida albicans hypha. The minimal inhibitory concentration(MIC) of berberine hydrochloride against clinical and standard C. albicans strains was detected by micro liquid-based dilution method; the effect of berberine hydrochloride on the colony formation of C. albicans SC5314 was investigated by spot assay; the effect of berberine hydrochloride on the metabolism of C. albicans SC5314 hypha was checked by XTT reduction assay, and the viability of C. albicans SC5314 hypha was tested by fluorescent staining assay. The effect of berberine hydrochloride on the morphology of C. albicans SC5314 hypha was examined by scanning electron microscope. The changes in the cell wall of C. albicans SC5314 hypha after berberine hydrochloride treatment were detected by transmission electron microscopy. The effect of berberine hydrochloride on β-glucan from C. albicans SC5314 was detected by flow cytometry. The effect of berberine hydrochloride on hypha-specific gene ECE1 and β-glucan synthase genes FKS1 and FKS2 in C. albicans was examined by qRT-PCR. The results showed that berberine hydrochloride showed a strong inhibitory effect on both clinical and standard strains of C. albicans, and the MIC was 64-128 μg·mL~(-1). Spot assay, XTT redunction assay and fluorescent staining assay showed that with the increase of berberine hydrochloride concentration, the viability of C. albicans SC5314 gradually decreased. The transmission electron microscopy scanning assay showed that this compound could cause cell wall damage of C. albicans. The flow cytometry analysis showed the exposure degree of C. albicans β-glucan. The qRT-PCR further showed that berberine hydrochloride could significantly down-regulate hypha-specific gene ECE1 and β-glucan synthase-related gene FKS1 and FKS2. In conclusion, this compound can down-regulate C. albicans and β-glucan synthase-related gene expressions, so as to destroy the cell wall structure of C. albicans, expose β-glucan and damage the integrity of the wall.

Micro-particulate Ganoderma lucidum spore β-glucanin enhances the antitumor activity of gemcitabin via remodeling immunosuppressive microenvironment in Lewis lung cancer / 药学学报

Gemcitabine (GEM) is a commonly used drug in the clinical treatment of non-small cell lung cancer. Due to the accumulation of cells mediating immune escape and T cell depletion after chemotherapy, tumor microenvironment (TME) tends to be immunosuppressive status, which ultimately leads to tumor metastasis. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. Therefore, we observed the immunomodulatory effects of micro-particulate Ganoderma lucidum spore β-glucan (PGSG) on macrophages in vitro experiments. Next, mice subcutaneous Lewis lung cancer models were established to observe the anti-tumor effects of PGSG through oral administration of PGSG combined with GEM. Flow cytometry analysis was used to analyze the ratio of anti-tumor T cells in tumors and spleen, as well as the proportion of myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM) and regulatory cells (Tregs). The results showed that PGSG can up-regulate the expression of major histocompatibility antigens (MHC-II), CD40, CD86 and CD80 on the surface of macrophages, enhance the ability to phagocytosis of neutral red and further mediate the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-10 (IL-10). In vivo experiments, combined administration can significantly decrease the volume and weight of tumors, reduce the ratio of MDSC (CD11b+Gr-1+), M-MDSC (CD11b+Ly6G-Ly6Chigh) and Treg (CD4+Foxp3+). At the same time, PGSG promoted the conversion of M2 (F4/80+CD206+) to M1 (F4/80+MHC-II+) and enhanced the response of helper T cell-1 (Th1) (CD4+IFN-γ+) and cytotoxic T lymphocyte (CTL) (CD8+IFN-γ+), which is of great significance for killing tumors. These results suggest that PGSG can regulate innate and adaptive antitumor immune responses, reshape the immunosuppressive microenvironment and enhance the anti-lung cancer effect of GEM.

Synthesis of novel papulacandin D analogs and evaluation of their antifungal potential

Systemic fungal infections are a growing problem in contemporary medicine and few drugs are licensed for therapy of invasive fungal infections. Differences between fungi and humans, like the presence of a cell wall in fungal cells, can be explored for designing new drugs. (1,3)-β-D-glucan synthase, an enzyme that catalyzes the synthesis of (1,3)-β-D-glucan, a structural and essential component of the fungal cell wall, is absent in mammals and this makes it an excellent target for the development of new antifungal agents. Papulacandins are a family of natural antifungal agents targeting (1,3)-β-D-glucan synthase. In this study we describe the synthesis and biological evaluation of two new Papulacandin analogs as potential (1,3)-β-D-glucan synthase inhibitors.

Effect of High β-glucan Barley on Postprandial Blood Glucose and Insulin Levels in Type 2 Diabetic Patients

Alkali extraction of Ganoderma lucidum β-glucan and its anti-tumor immune regulation / 药学学报

In this study, an immunostimulating particulate β-glucan was isolated from a hot alkaline extract of the fruiting bodies of Ganoderma lucidum. The optimum conditions of 8 hours treatment time, 1∶20 solid - liquid ratio and 55 ℃ for the alkaline extract process were obtained after investigating by single-factor experiments and Box-Benhnken design in terms of the Ganoderma lucidum particulate β-glucan (GLG) increment, and these conditions resulted in a GLG yield of 8.57%. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. The result showed that resident macrophages were effectively activated by GLG, such as with the up-regulation of co-stimulatory molecules, the secretion of cytokines and phagocytic uptake. GLG could also promote the proliferation of spleen lymphocytes in mice. In addition, IFN-γ production of spleen CD4+ T cells and cytotoxic T lymphocyte (CTL) responses were significantly enhanced on GLG orally treatment, which ultimately resulted in significantly decreased tumor burden. Taken together, these data suggest that GLG might act as an immune stimulator to exert antitumor effects.

Β-Glucan of candida albicans cell wall extract inhibits salmonella typhimurium colonization by potentiating cellular immunity (cd8 + and cd4 + t cells)

Abstract INTRODUCTION: Antimicrobial resistance has been reported in the drugs used for the treatment of typhoid fever. The immunomodulatory substance β-glucan can be used as an alternative therapy as it potentiates host immunity. The aims of this study are to observe the effect of Candida albicans cell wall (CCW) extract towards host immunity (TCD8+ and TCD4+ cells in spleen, intestinal sIgA) and its capacity to kill Salmonella in the intestine and liver of typhoid fever mice models. METHODS: Typhoid fever mice models were created by infecting mice with S. Typhimurium orally. Mice were divided into four groups: the Non-Infected, Infected, CCW (infected mice treated with 300 µg CCW extract/mouse once a day), and Ciprofloxacin groups (infected mice treated with 15 mg/kg BW ciprofloxacin twice a day). RESULTS: Secretory IgA (sIgA) concentrations of mice in the CCW group remained unchanged. However, their TCD4+ and TCD8+ cells increased substantially compared to those in the Non-Infected group. In the Ciprofloxacin group, sIgA concentrations increased markedly compared to those in the Non-Infected and CCW groups; TCD4+ and TCD8+ cells also increased significantly compared to those in the Infected Group, but not significant compared to those in the CCW group. Colonization of S. Typhimurium in the intestine and liver decreased significantly in the CCW and Ciprofloxacin groups compared to that in the Infected group, with the lowest reduction being found in the Ciprofloxacin group. CONCLUSIONS The inhibition of S. Typhimurium colonization by CCW is associated with the increase in TCD4+ and TCD8+ cells.

Beta-glucan attenuates cerebral ischemia/reperfusion-induced neuronal injury in a C57BL/J6 mouse model

Beta-glucans (ßg), that have many useful effects on human health, are natural polysaccharides. Our aim in this study was to determine useful effect of ßg against oxidative and neuronal damage caused by global cerebral ischemia/reperfusion (IR) in stroke imitated mice via surgical operation. A total of 40 mice divided into four equal groups randomly. The group 1 (sham operated) was kept as control. Bilateral carotid arteries of subjects in group 2 (I/R) and group 4 (I/ R + ßg) were clipped for 15 min, and the mice in group 4 (I/R + ßg) were treated with ßg (50 mg/kg/day), while the mice in group 2 (I/R) were treated with only vehicle for 10 days. The mice of group 3 (ßg) were treated with ßg for 10 days without carotid occlusion. Global cerebral I/R significantly increased oxidative stress and decreased members of anti-oxidant defense system. In addition, I/R caused histopathological damage in the brain tissue. However, ßg treatment ameliorated both oxidative and histopathological effects of I/R. Our present study showed that ßg treatment significantly ameliorated oxidative and histological damage in the brain tissue caused by cerebral I/R. Therefore, ßg treatment can be used as supportive care for ischemic stroke patients

Effect of High β-glucan Barley on Postprandial Blood Glucose Levels in Subjects with Normal Glucose Tolerance: Assessment by Meal Tolerance Test and Continuous Glucose Monitoring System

The effect of white rice (WR) mixed with high β-glucan-containing barley at 50% on improvement of postprandial blood glucose levels was assessed by meal tolerance test and continuous glucose monitoring (CGM) in 15 healthy subjects with normal glucose tolerance (age 31.6 ± 12.9 years old, 4 males and 11 females). A meal tolerance test (500 kcal) was conducted using 2 types of test meals: a test meal only with WR and a test meal WR mixed 50% barley, and the side dish was the same in both meals. Blood glucose levels of the subjects 180 minutes after ingestion of the test meals were compared. In addition, a CGM device was attached to the subjects for 2 days when the WR or barley as a staple food was provided 3 times a day for consecutive days, and the daily variation of glucose was investigated. The glucose levels 30 minutes after dietary loads and the area under the blood concentration-time curve over 180 minutes were significantly decreased in the barley consumption group. In CGM, 24-hour mean blood glucose and 24-hour standard deviation of blood glucose were also significantly decreased after ingestion of the barley. Postprandial glucose level elevation was suppressed by mixing high-β-glucan barley with WR in subjects with normal glucose tolerance.

Role of recombinant major surface glycoprotein C consensus antigen of Pneumocystis jirovecii in serological diagnosis of Pneumocystis pneumonia / 中国感染与化疗杂志

Objective To evaluate the clinical value of recombinant major surface glycoprotein C(Msg C)consensus antigen of Pneumocystis jirovecii in serological diagnosis of Pneumocystis pneumonia(PCP), and explore serological diagnosis for PCP. Methods ELISA method was established for testing IgM antibody of Pneumocystis jirovecii Msg C consensus antigen. Serum antiMsg C consensus antigen IgM antibody and(1, 3)-β-D glucan were determined in 48 patients at high risk of PCP and 51 healthy subjects. The results of ELISA and(1, 3)-β-D glucan assay were compared with the results of PCR in bronchoalveolar lavage fluid. Results In a total of 99 specimens, Msg C consensus antigen IgM antibody detection(28.3％, 28/99)showed similar positive rate as(1, 3)-β-D glucan assay(25.3％, 25/99)(P>0.05). For the 48 patients at high risk of PCP, the positive rate of Msg C consensus antigen IgM antibody and(1, 3)-β-D glucan assay was 35.4％(17/48)and 33.3％(16/48), respectively(P>0.05). The two methods showed 67.7％ agreement in testing 99 specimens and 52.1％ agreement in testing 48 high-risk specimens. The bronchial lavage fluid samples of 48 patients at high risk were also tested by PCR. The result was positive in 15 cases(31.3％), showing no significant difference from Msg C consensus antigen IgM antibody test(P=0.665). The agreement between Msg C consensus antigen IgM antibody test and PCR was 58.3％. The agreement with PCR result increased to 84.0％ in the 25 specimens with the same result by two serological methods.When taking the positive result of either serological method as reference, serological method can detect majority of the PCR positive cases(86.7％, 13/15). Conclusions IgM antibody against Msg C consensus antigen in combination with serological marker(1, 3)-β-D glucan is valuable for PCP diagnosis. Further examination such as lower respiratory tract specimen PCR and conventional cytology should be carried out to confirm the diagnosis when both IgM antibody against Msg C consensus antigen and(1, 3)-β-D glucan are positive.

Clinical features of candidemia and the diagnostic value of (1, 3) -β-D glucan / 中国感染与化疗杂志

Objective To understand the etiology and clinical characteristics of candidemia, and the diagnostic value of(1, 3)-β-Dglucan. Methods This analysis included 31 patients with candidemia, 39 patients with Candida deep colonization, and 50 healthy subjects, who were enrolled from Wuyi Chinese Hospital Affiliated to Jinan University during the period from September 2015 to March 2018. Clinical data such as fungal culture, clinical features, and serum(1, 3)-β-D-glucan level were analyzed and compared between groups. Results Overall, 13 strains of Candida albicans and 18 strains of non-albicans Candida were isolated from the 31 patients with candidemia. The incidence of candidemia was associated with old age(>65 years), prior surgery(≤7 days), indwelling catheter(≥2 catheters and lasting ≥5 days), duration of mechanical ventilation(≥5 days)(P<0.05), but not associated with sex, underlying disease, prior use of anmicrobial and antifungal agents, immunosuppressant or glucocorticoid, or hypoproteinemia(P>0.05). Serum level of(1, 3)-β-D-glucan was significantly higher in candidemia patients than in the patients with candida deep colonization and healthy controls(P<0.05). The sensitivity and specificity of(1, 3)-β-D-glucan in diagnosing candidemia were 87.1％ and 96.0％, respectively. The level of(1, 3)-β-D-glucan was significantly higher in candidemia with bacterial infection than candidemia without bacterial infection(P<0.05). The level of of(1, 3)-β-D-glucan was also significantly higher in the candidemia caused by Candida albicans alone than that caused by non-albicans Candida alone(P<0.05). Conclusions Non-albicans Candida is more prevalent than Candida albicans in candidiasis, but Candida albicans is still the most important Candida species. The incidence of candidemia is asociated with advanced age(>65 years), prior surgery within 7 days, indwelling catheters(≥2 catheters and lasting ≥5 days), and mechanical ventilation(≥5 days). Serum(1, 3)-β-D-glucan level is valuable for early diagnosis of candidemia.

Clinical value of plasma (1-3)-β-D-glucan for diagnosis of fungal bloodstream infection / 第二军医大学学报

[Abstract] Objective To investigate the clinical value of plasma (1-3)-β-D-glucan test (G test) for diagnosis of fungal bloodstream infection. Methods The blood samples for fungal culturing and G test were collected in Changhai Hospital of Naval Medical University (Second Military Medical University) from Jan. 2015 to Dec. 2017. The department distribution and strain distribution of 264 positive specimens detected by fungal blood culture were analyzed. A total of 1 678 samples were collected during this period for fungal blood culture and plasma G test. Taking fungal blood culture as the criterion, with a cut-off of 100.5 pg/mL for G test, we analyzed the sensitivity, specificity, positive forecast value, and negative forecast value of G test for diagnosis of fungal bloodstream infection. Statistical analysis was performed using SPSS 19.0 software, and the diagnostic value of G test for bloodstream infection was judged by the receiver operating characteristic (ROC) curve. Results A total of 264 strains of fungal blood culture were positive from 2015 to 2017, mainly from the departments of hepatobiliary surgery (81 strains), cardiac surgery (57 strains), emergency (24 strains), thoracic surgery (22 strains), and hematology (16 strains). Candida is the main genus, of which Candida parapsilosis is the most common one, with 142 strains (53.8%), followed by Candida corneum (36 stains, 13.6%), Candida albicans (20 strains, 7.6%) and Candida tropical (18 strains, 6.8%). Taking fungal blood culture as the criterion, we found that the sensitivity, specificity, positive forecast value, and negative forecast value of G test for diagnosis of fungal infection were 61.3%, 87.9%, 31.1%, and 96.2%, respectively. ROC curve analysis showed that G test was valuable for diagnosis of fungal bloodstream infection, with the area under the curve being 0.771 (95% confidence interval: 0.723-0.819). Among 137 cases of bloodstream infection, 102 cases (69.6%) were tested for G test 2-5 d before blood culture, and 71 cases were positive. Conclusion Plasma G test kit is still ideal in terms of specificity and has a certain clinical value for the early diagnosis of fungal bloodstream infection.