Advancing cancer immunotherapy through siRNA-based gene silencing for immune checkpoint blockade.

Cancer immunotherapy represents a revolutionary strategy, leveraging the patient's immune system to inhibit tumor growth and alleviate the immunosuppressive effects of the tumor microenvironment (TME). The recent emergence of immune checkpoint blockade (ICB) therapies, particularly following the first approval of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors like ipilimumab, has led to significant growth in cancer immunotherapy. The extensive explorations on diverse immune checkpoint antibodies have broadened the therapeutic scope for various malignancies. However, the clinical response to these antibody-based ICB therapies remains limited, with less than 15% responsiveness and notable adverse effects in some patients. This review introduces the emerging strategies to overcome current limitations of antibody-based ICB therapies, mainly focusing on the development of small interfering ribonucleic acid (siRNA)-based ICB therapies and innovative delivery systems. We firstly highlight the diverse target immune checkpoint genes for siRNA-based ICB therapies, incorporating silencing of multiple genes to boost anti-tumor immune responses. Subsequently, we discuss improvements in siRNA delivery systems, enhanced by various nanocarriers, aimed at overcoming siRNA's clinical challenges such as vulnerability to enzymatic degradation, inadequate pharmacokinetics, and possible unintended target interactions. Additionally, the review presents various combination therapies that integrate chemotherapy, phototherapy, stimulatory checkpoints, ICB antibodies, and cancer vaccines. The important point is that when used in combination with siRNA-based ICB therapy, the synergistic effect of traditional therapies is strengthened, improving host immune surveillance and therapeutic outcomes. Conclusively, we discuss the insights into innovative and effective cancer immunotherapeutic strategies based on RNA interference (RNAi) technology utilizing siRNA and nanocarriers as a novel approach in ICB cancer immunotherapy.

Combined effect of heating temperature and content of pectin on the textural properties, rheology, and 3D printability of potato starch gel.

Three-dimensional (3D) printing is one of the emerging techniques which fabricates customized foods with desired sensory characteristics. Rheological properties of 3D printing materials are vitally important in printability which govern the flowability and structural stability. Due to its unique gel-forming characteristics, potato starch has been extensively used in myriad food applications, such as 3D printing. However, little attention has been paid to the combined effect of heating temperature and pectin addition on the properties of potato starch gels. Thus, this study investigated the impact of different pectin contents (1, 1.5, and 2 %) on printability and the rheological and textural properties of potato starch gels heated at different temperatures (70, 80, and 90 °C). The gel heating temperature governs pectin-driven modifications in potato starch gels. Pectin addition increased the 3D printability, viscosity, storage modulus, hardness, gumminess, and springiness of starch gel at higher temperatures (80 °C and 90 °C). In contrast, at lower temperatures (70 °C), pectin addition decreased printability, viscosity, storage modulus, hardness, gumminess, and springiness. Therefore, the gel heating temperature influences the impact of pectin on printability, rheology, and textural properties. Accordingly, the combined effects of pectin and heating temperature should be considered in pectin-based 3D food-printing ink formulations.

Individualized herbal prescriptions for delayed union: A case series.

Background Bone fractures are important clinical events for both patients and professionals. Active treatment options are limited for delayed unions and for nonunions; surgery is common but not entirely risk-free. This report describes three cases of delayed union successfully treated with herbal decoction. Participants Three patients had trapezoid and 3rd metacarpal bone fractures, 2nd, and 5th metatarsal bone fractures, respectively. All three patients were diagnosed with delayed union by an independent orthopedic surgeon based on computed tomography (CT) scan/radiographic imaging and fracture duration without a healing process. Patients took herbal decoction, Jeopgol-tang, with individually added herbs based on symptom manifestations, twice daily for 56, 85 and 91 days with no additional interventions except for a splint that they had been wearing since fracture diagnosis. Outcomes Improvement of delayed union was evaluated using radiographic imaging or CT during treatment with Jeopgol-tang. Results After taking herbal medicine, callus and bony bridging were confirmed on follow-up imagings and the patients described their experience with pain reduction at an interview after recovery. Conclusions This case series suggests that the herbal decoction Jeopgol-tang warrants further investigation to establish its role as a complementary and integrative medicine treatment option for delayed unions.

Inhibitory effects of Centella asiatica (L.) Urban on enlarged prostate through androgen receptor and PI3K/Akt signaling pathways.

Centella asiatica (L.) Urban (C. asiatica) is a traditional herbal medicine that has been used for wound healing and anti-inflammation since ancient times. Various biological effects of C. asiatica ethanolic extract (CAE) were previously reported. However, in our previous study, C. asiatica aqueous extract (CAA) exhibited higher inhibitory activity on benign prostatic hyperplasia (BPH) than CAE. Therefore, the aim of this study was to investigate the effect of CAA on BPH, and elucidate the inhibitory mechanism through in vitro and in vivo experiments as well as metabolite analysis of CAA. A BPH rat model was induced by daily subcutaneous injection of testosterone propionate (TP, 3 mg kg-1) dissolved in corn oil for 4 weeks after castration. The experimental group, the CAA treatment group, was orally administered CAA (100 mg kg-1) for 4 weeks while inducing prostatic hyperplasia. Saw palmetto extract (Saw, 100 mg kg-1) and Finasteride (Fi, 1 mg kg-1) were used as positive controls and were administered orally for 4 weeks. CAA significantly inhibited androgen receptor signaling related factors overexpressed by dihydrotestosterone (DHT) treatment in prostate cell lines. Afterwards, the testosterone-induced BPH model was used to verify the alleviation efficacy of CAA in prostatic hyperplasia. Prostate size and the thickness of the prostate tissue epithelium were significantly decreased in the group treated with CAA compared to those in the BPH group. The results of protein expression in the prostate tissue confirmed that CAA inhibited androgen receptor signaling in BPH and decreased the expression of growth factors. Moreover, CAA suppressed the expression of the PI3K/Akt pathway and cell proliferation-related factors compared to the BPH group. Taken together, these results indicate that CAA improves the inhibitory efficacy of BPH by inhibiting the androgen receptor and PI3K/Akt pathways, suggesting that CAA may be a promising candidate for biopharmaceutical formulations of BPH.

Comparative Analysis of Metabolite Profiling of Momordica charantia Leaf and the Anti-Obesity Effect through Regulating Lipid Metabolism.

This study investigated the effects of Momordica charantia (M. charantia) extract in obesity and abnormal lipid metabolism in mice fed high fat diet (HFD). Fruit, root, stem, and leaf extracts of M. charantia were obtained using distilled water, 70% ethanol and 95% hexane. M. charantia leaf distilled water extract (MCLW) showed the highest antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity tests and reducing power. Metabolite profiles of M. charantia leaf extracts were analyzed for identification of bioactive compounds. HFD-fed mice were treated with MCLW (oral dose of 200 mg/kg/d) for 4 weeks. MCLW reduced lipid accumulation, body weight, organ weight, and adipose tissue volume and significantly improved glucose tolerance and insulin resistance in HFD mice. Furthermore, MCLW administration reduced serum total cholesterol and low-density lipoprotein cholesterol, and increased serum high-density lipoprotein cholesterol compared with HFD mice. Moreover, MCLW significantly reduced the levels of serum urea nitrogen, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase; alleviated liver and kidney injury. MCLW decreases expression of genes that fatty acid synthesis; increase the expression of catabolic-related genes. These results indicate that MCLW has an inhibitory effect on obese induced by high fat diet intake, and the mechanism may be related to the regulation of abnormal lipid metabolism in liver and adipose tissue, suggesting that MCLW may be a suitable candidate for the treatment of obesity.

Increased sensitization rates to tree pollens in allergic children and adolescents and a change in the pollen season in the metropolitan area of Seoul, Korea.

INTRODUCTION: Children with allergies are at greater risk of becoming sensitized to allergenic pollens in response to environmental changes. This study investigated the relationship between changes in pollination associated with meteorologic changes and the sensitization rates of children to tree pollen allergens in the metropolitan area of Seoul, Korea. METHODS: The study population consisted of 8,295 children who visited the pediatric allergy clinics at Hanyang University Seoul and Guri Hospital for allergy symptoms between January 1, 1998, and December 31, 2019. Pollen was collected at the two hospitals during the study using a Burkard 7-day sampler. Meteorologic data were obtained from the National Weather Service. RESULTS: Among the major tree pollens, the largest increase in allergic sensitization was to oak, hazel, and alder pollens (0.28% annually). The pollen-sensitization rates increased annually within younger age groups. The duration of the pollen season was 98 days in 1998 and 140 days in 2019. Positive correlations were determined between the duration of the pollen season and the rates of sensitization to tree pollens, as well as between the pollen-sensitization rates and increasing temperature. CONCLUSIONS: This study demonstrated the correlation between weather changes and the resulting changes in the pollen season with sensitization rates to allergenic pollens in children living in the Seoul metropolitan area. An annual increase in sensitization rates in younger children was determined. This pattern is expected to continue due to continuing climate change.

The Impact of Climate Change on Pollen Season and Allergic Sensitization to Pollens.

Pollens are a major cause of seasonal allergic diseases. Weather may alter the production of pollens. Increased atmospheric temperatures lead to earlier pollination of many plants and longer duration of pollination, resulting in extended pollen seasons, with early spring or late winter. Longer pollen seasons increase duration of exposure, resulting in more sensitization, and higher pollen concentrations may lead to more severe symptoms. Climate changes in contact to pollens may affect both allergic sensitization and symptom prevalence with severity. The future consequences of climate change, however, are speculative, because the influence on humans, is complex.

Effects of Mechanical Drying on the Removal of Pollen Allergens.

PURPOSE: Pollen may spread indoors through clothes contaminated during outdoor activities. This study aimed to evaluate the pollen removal efficacy of a mechanical dryer. METHODS: Cotton clothes served as laundry, and fabrics measuring 2 × 5 cm served as test samples. Pollen was spread evenly on the test fabrics. The fabrics were then fixed on the cloth and left for 8 h to imitate real-life conditions. This experiment was conducted under 2 conditions, wet (after washing clothes) and dry (without washing). After drying, we counted pollen on the test fabrics to evaluate the pollen removal rate. We measured the remaining allergens in extracts from the contaminated fabrics after mechanical drying. The concentrations of allergens (Amb a 1, Bet v 1, Crp j 1, and Phl p 1) in each extracted solution were measured using 2-site ELISA. RESULTS: For ragweed, Japanese cedar, birch, and timothy grass, the mean pollen removal ratios for the dry samples were 99.88 ± 0.09%, 99.96 ± 0.03%, 99.89 ± 0.02%, and 99.82 ± 0.11%, respectively, and those for the wet samples were 98.83 ± 0.87%, 97.91 ± 1.81%, 97.29 ± 1.19%, and 96.3 ± 0.92%, respectively. Further, for the pollen allergens Amb a 1 [ragweed], Crp j 1 [Japanese cedar], Bet v 1 [birch], and Phl p 1 [timothy grass], the mean pollen allergen removal ratios for the dry samples were 99.81 ± 0.06%, 99.94 ± 0.23%, 99.90 ± 0.11%, and 99.84 ± 0.17%, respectively, and those for the wet samples were 98.11 ± 0.14%, 96.04 ± 1.52%, 97.21 ± 0.83%, and 95.23 ± 0.92%, respectively. There was no statistically significant difference for each species. CONCLUSIONS: Mechanical drying effectively removed pollen and allergens from dry and wet fabrics. We expect that further studies on the removal of other indoor allergens would contribute to improved environmental control for allergy patients.

Sulforaphane mitigates mast cell-mediated allergic inflammatory reactions in in silico simulation and in vitro models.

Objectives: Sulforaphane, a major ingredient isolated from Brassica oleracea var. italica (broccoli), is known to exhibit anti-inflammatory, anti-cancer, and anti-diabetic effects. In this study, we employed an in vitro model of phorbol 12-myristate 13-acetate and a23187 (PMACI)-stimulated human mast cells (HMC-1 cells) to investigate the anti-allergic inflammatory effects and mechanisms of sulforaphane and Brassica oleracea var. italica extracts.Methods: Cytokine levels were measured by ELISA and quantitative real-time-PCR methods. Caspase-1 activity was determined by caspase-1 assay. Binding mode of sulforaphane within caspase-1 was determined by molecular docking simulation. Protein expression was determined by Western blotting.Results: Water extract of Brassica oleracea var. italica (WE) significantly reduced thymic stromal lymphopoietin (TSLP) secretion and caspase-1 activity on activated HMC-1 cells. In the molecular docking simulation and in vitro caspase-1 assays, sulforaphane regulated caspase-1 activity by docking with the identical binding site of caspase-1. Sulforaphane significantly inhibited the levels of inflammatory mediators including TSLP, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-8 in a dose-dependent manner. Immunoblotting experiments revealed that sulforaphane and WE reduced translocation of NF-κBp65 into the nucleus and phosphorylation of IκBα in the cytosol. Furthermore, phosphorylation of mitogen-activated protein kinases (MAPK) was down-regulated by treatment with sulforaphane or WE.Conclusion: Our findings suggest that sulforaphane and WE have anti-allergic inflammatory effects by intercepting caspase-1/NF-κB/MAPKs signaling pathways.

Inhibitory Effect of Centella asiatica Extract on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused mainly by immune dysregulation. This study explored the anti-inflammatory and immunomodulatory effects of the Centella asiatica ethanol extract (CA) on an AD-like dermal disorder. Treatment with CA inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a dose-dependent manner in inflammatory stimulated HaCaT cells by interferon-γ (IFN-γ) and TNF-α-triggered inflammation. Eight-week-old BALB/c mice treated with 2,4-dinitrochlorobenzene (DNCB) were used as a mouse model of AD. In AD induce model, we had two types treatment of CA; skin local administration (80 µg/cm2, AD+CA-80) and oral administration (200 mg/kg/d, AD+CA-200). Interestingly, the CA-treated groups exhibited considerably decreased mast cell infiltration in the ear tissue. In addition, the expression of IL-6 in mast cells, as well as the expression of various pathogenic cytokines, such as TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, iNOS, COX-2, and CXCL9, was reduced in both AD+CA-80 and AD+CA-200 groups. Collectively, our data demonstrate the pharmacological role and signaling mechanism of CA in the regulation of allergic inflammation of the skin, which supports our hypothesis that CA could potentially be developed as a therapeutic agent for AD.

Injectable dual-scale mesoporous silica cancer vaccine enabling efficient delivery of antigen/adjuvant-loaded nanoparticles to dendritic cells recruited in local macroporous scaffold.

Despite the potential of nanoparticle-based vaccines, their therapeutic efficacy for cancer immunotherapy is limited. To elicit robust antigen-specific adaptive immune responses, antigen-loaded nanoparticles are employed for transport into host dendritic cells (DCs); however, only a minority of the nanoparticles can be engulfed by host DCs. Herein, an injectable dual-scale mesoporous silica vaccine consisting of mesoporous silica microrods (MSRs) coupled with mesoporous silica nanoparticles (MSNs) is introduced. The MSRs form a three-dimensional macroporous scaffold after injection, and the subsequent release of DC-recruiting chemokine loaded in the mesopores of MSRs leads to the recruitment of numerous DCs into the scaffold. Subsequently, MSNs co-loaded with an antigen and Toll-like receptor 9 agonist, which exist in interparticle space of the MSR scaffold, are internalized by the recruited DCs, leading to the generation of antigen-presenting activated DCs. Strikingly, the MSR-MSN dual-scale vaccine generates a significantly larger number of antigen-specific T cells and inhibits melanoma growth to a greater extent compared with a single MSR or MSN vaccine. Moreover, the dual-scale vaccine is synergized with an immune checkpoint inhibitor to inhibit tumor growth in tumor-bearing mice. The findings suggest that the MSR is a novel platform for delivering nanoparticle vaccines for the enhancement of cancer immunotherapy.

Metabolomic Analysis of Morus Cultivar Root Extracts and Their Ameliorative Effect on Testosterone-Induced Prostate Enlargement in Sprague-Dawley Rats.

We investigated the metabolite changes of Morus roots (MRs) according to different cultivar families (Simheung, Daesim, Cheong-il, Sangchon, Daeseong, Suhong, Suwon, and Igsu) using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to understand the relationship between different cultivars and metabolite changes. Data were analyzed by partial least squares discriminant analysis (PLS-DA), and samples were successfully separated in PLS-DA scores. Eight metabolites in the electrospray ionization (ESI)-positive mode and 16 metabolites in the ESI-negative mode contributed to the separation in PLS-DA. Our data suggest that comparative analysis of MR metabolites according to different cultivars is useful to better understand the relationship between the different cultivars and metabolite changes. Furthermore, we analyzed the MRs for their ability to improve benign prostatic hyperplasia (BPH). LNCaP cells were used to evaluate the prostate-specific antigen (PSA) inhibitory activity of MRs, and, amongst them, the extract with the highest activity was selected. Igsu demonstrated the highest inhibition effect of prostate-specific antigen (PSA) expression among the MR cultivars. Igsu was also evaluated by administration in a testosterone-induced benign prostatic hyperplasia model in Sprague-Dawley rats. Igsu was shown to ameliorate BPH as evidenced by the prostate index, expression of androgen receptor (AR) signaling-related protein, growth factors, cell proliferation-related proteins, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling proteins, and histological analysis. Hence, this study strongly suggests that Igsu may have a beneficial effect of on BPH.

Efficacy and Mechanism of Polymerized Anthocyanin from Grape-Skin Extract on High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease.

We investigated the therapeutic potential of polymerized anthocyanin (PA) on a nonalcoholic fatty liver disease (NAFLD) model in mice. C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks to establish the NAFLD mouse model and randomly divided into four groups: control diet (con), NAFLD mice treated with saline (NAFLD), NAFLD mice treated with PA (PA), and NAFLD mice treated with orlistat (Orlistat) for four weeks. Mice were euthanized at the end of the four weeks. Total cholesterol (TC) and triglyceride (TG) levels were estimated, and pathological changes in the liver, white adipose tissue, and signaling pathways related to lipid metabolism were evaluated. Results revealed that the body, liver, and white fat weight of the NAFLD group was significantly increased compared to that of the con group, while that of the PA group showed significant reduction. NAFLD led to an increase in blood lipids in mice (except for HDL). Conversely, PA effectively reduced TC and LDL-C. Compared to the control group, the degree of steatosis in the mice of PA group was decreased. Moreover, PA also regulated the NAFLD signaling pathway. In agreement with improved lipid deposition, PA supplementation inhibited the activation of inflammatory pathways, depressing oxidative stress through increased antioxidant levels, and increasing ß-oxidation to inhibit mitochondrial dysfunction. Taken together, our results demonstrate that PA can improve the liver function of NAFLD mice, regulating blood lipids, reducing liver-fat accumulation, and regulating lipid metabolism.

Effect of Paecilomyces tenuipes Extract on Testosterone-Induced Benign Prostatic Hyperplasia in Sprague-Dawley Rats.

: Benign prostatic hyperplasia (BPH) is one of the major public health concerns, which has a high prevalence rate and causes significant decline in men's quality of life. BPH is highly related to sexual hormone metabolism and aging. In particular, dihydrotestosterone (DHT), to which testosterone is modified by 5α-reductase (5AR), has a significant effect on BPH development. DHT binds to an androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1); then, it induces the proliferation of a prostate cell and expression of prostate specific antigen (PSA). Paecilomyces tenuipes (P. tenuipes) is a mushroom that has been popularized by the artificial cultivation of fruiting bodies based on silkworms by researchers from the Republic of Korea. In a previous study, we identified the effect of PE on PSA mRNA expression in LNCaP cells. This suggests that PE may have an inhibitory effect on androgen signaling. Therefore, we confirmed the expression of androgen signaling-related factors, such as AR, SRC-1, and PSA in LNCaP. Furthermore, we confirmed the androgen signaling inhibitory effect of PE using the testosterone propionate (TP)-induced BPH rat model. A BPH rat model was established with a four-week treatment of daily subcutaneous injections of testosterone propionate (TP, 3 mg/kg) dissolved in corn oil after castration. The rats in the treatment group were orally gavaged P. tenuipes extract (PE), finasteride (Fi), or saw palmetto extract (Saw) with TP injection. DHT induced an increase in the expression levels of AR, SRC-1, and PSA proteins in LNCaP cells. On the contrary, the PE treatment reduced the expression levels. In vivo, the BPH group showed an increase in prostate size compared with the control group. The PE gavaged group showed a decrease in prostate size compared with the BPH group. In addition, the protein expressions of AR, 5AR2, and PSA were significantly lower in the PE gavaged group than BPH group in prostate tissue. These results suggest the beneficial effects of PE on BPH via the modulation of AR signaling pathway.

The Role of Momordica charantia in Resisting Obesity.

Momordica charantia (M. charantia), commonly known as bitter gourd, bitter melon, kugua, balsam pear, or karela, is a tropical and sub-tropical vine belonging to the Cucurbitaceae family. It has been used to treat a variety of diseases in the traditional medicine of China, India, and Sri Lanka. Here, we review the anti-obesity effects of various bioactive components of M. charantia established at the cellular and organismal level. We aim to provide links between various bioactive components of M. charantia and their anti-obesity mechanism. An advanced search was conducted on the worldwide accepted scientific databases via electronic search (Google Scholar, Web of Science, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, SciFinder, CNKI) database with the query TS = "Momordica charantia" and "obesity". Information was also obtained from International Plant Names Index, Chinese Pharmacopoeia, Chinese herbal classic books, online databases, PhD and MSc dissertations, etc. First, studies showing the anti-obesity effects of M. charantia on the cells and on animals were classified. The major bioactive components that showed anti-obesity activities included proteins, triterpenoids, saponins, phenolics, and conjugated linolenic acids. Their mechanisms included inhibition of fat synthesis, promotion of glucose utilization, and stimulation of auxiliary lipid-lowering activity. Finally, we summarized the risks of excessive consumption of M. charantia and the application. Although further research is necessary to explore various issues, this review establishes the therapeutic potential of M. charantia and it is highly promising candidate for the development of anti-obesity health products and medicines.

Mesoporous Silica as a Versatile Platform for Cancer Immunotherapy.

Immunotherapy has been recognized for decades as a promising therapeutic method for cancer treatment. To enhance host immune responses against cancer, antigen-presenting cells (APCs; e.g., dendritic cells) or T cells are educated using immunomodulatory agents including tumor-associated antigens and adjuvants, and manipulated to induce a cascading adaptive immune response targeting tumor cells. Mesoporous silica materials are promising candidates to improve cancer immunotherapy based on their attractive properties that include high porosity, high biocompatibility, facile surface modification, and self-adjuvanticity. Here, the recent progress on mesoporous-silica-based immunotherapies based on two material forms is summarized: 1) mesoporous silica nanoparticles (MSNs), which can be internalized into APCs, and 2) micrometer-sized mesoporous silica rods (MSRs) that can form a 3D space to recruit APCs. Subcutaneously injected MSN-based cancer vaccines can be taken up by peripheral APCs or by APCs in lymphoid organs to educate the immune system against cancer cells. MSR cancer vaccines can recruit immune cells into the MSR scaffold to induce cancer-specific immunity. Both vaccine systems successfully stimulate the adaptive immune response to eradicate cancer in vivo. Thus, mesoporous silica has potential value as a material platform for the treatment of cancer or infectious diseases.

Does the increase in ambient CO2 concentration elevate allergy risks posed by oak pollen?

Oak pollen is a major respiratory allergen in Korea, and the distribution of oak trees is expected to increase by ecological succession and climate change. One of the drivers of climate change is increasing CO2, which is also known to amplify the allergy risk of weed pollen by inducing elevated allergenic protein content. However, the impact of CO2 concentration on tree pollen is not clearly understood due to the experimental difficulties in carrying out extended CO2 treatment. To study the response of pollen production of sawtooth oak trees (Quercus acutissima) to elevated levels of ambient CO2, three open-top chambers at the National Institute of Forest Science in Suwon, Korea were utilized with daytime (8 am-6 pm) CO2 concentrations of ambient (× 1.0, ~ 400 ppm), × 1.4 (~ 560 ppm), and × 1.8 (~ 720 ppm) treatments. Each chamber had three sawtooth oak trees planted in September 2009. One or two trees per chamber matured to bloom in 2016. Five to six catkins were selected per tree and polyethylene bags were attached to collect pollen grains. The total number of catkins per tree was counted and the number and weight of pollen grains per catkin were measured. Oak allergen-Que a 1 (Allergon Co., Uppsala, Sweden)-was extracted and purified to make an ELISA kit by which the antigen levels in the pollen samples were quantified. Total pollen counts per tree of the × 1.4 and × 1.8 treatments showed significant increase of 353 and 1299%, respectively, from the × 1.0 treatment (p < 0.001). Allergenic protein contents at the × 1.4 and × 1.8 treatments also showed significant increase of 12 and 11%, respectively (p = 0.011). The × 1.8 treatment induced significant difference from the × 1.0 treatment in terms of pollen production and allergenic protein content, whereas the × 1.4 treatment showed mixed significance. In summary, the oak trees under the elevated CO2 levels, which are expected in the changing climate, produced significantly higher amount of pollen and allergenic protein than under the present air conditions.

Cereboost™, an American ginseng extract, improves cognitive function via up-regulation of choline acetyltransferase expression and neuroprotection.

In Alzheimer disease (AD), amyloid-beta (Aß) peptides induce the degeneration of presynaptic cholinergic system, in which decreased activity of enzyme choline acetyltransferase (ChAT) responsible for acetylcholine synthesis is observed. Cereboost™, an extract of American ginseng extract, contains a high concentration of Rb1 ginsenoside which is a well-known ingredient improving human cognitive function. We investigated the effects of Cereboost™ on learning and memory function of mice challenged with an Aß1-42 peptide and the underlying mechanisms in vitro. Cereboost™ protected against Aß1-42-induced cytotoxicity in F3.ChAT stem cells, and enhanced the ChAT gene expression. Aß1-42 injection into the mouse brain impaired the cognitive function, which was recovered by oral administration of Cereboost™. In addition, Cereboost™ restored brain microtubule-associated protein 2 and synaptophysin as well as acetylcholine concentration. The results demonstrate that Cereboost™ administration recovered the cognitive function of AD model animals by enhancing acetylcholine level via ChAT gene expression and neuroprotection.

Antimicrobial activities of ethanol and butanol fractions of white rose petal extract.

White rose (Rosa hybrida) petals were extracted with ethanol (EtOH) or butanol (BuOH), and tested for their antimicrobial activities against two species of Gram-positive bacteria, six species of Gram-negative bacteria, and two species of fungi. On in vitro antimicrobial assays, Helicobacter pylori and Propionibacterium acnes were highly susceptible to white rose petal extract (WRPE)-EtOH and WRPE-BuOH, leading to minimal inhibitory concentrations of 100 and 10 µg/mL for H. pylori and 400 and 40 µg/mL for P. acnes, respectively. In in vivo experiments, C57BL/6 mice were infected with H. pylori by intragastric inoculation (1 × 10(8) CFU/mouse) 3 times, and orally treated twice a day for 14 days with WRPE-EtOH and WRPE-BuOH. On a CLO kit assay, 200 mg/kg of WRPE-EtOH fully eliminated the bacteria from the gastric mucosa, and the effect of 100 mg/kg of ethanol fraction was similar to pantoprazole (30 mg/kg), displaying 75% elimination. WRPE-BuOH was more effective, exhibiting 75% elimination at 20 mg/kg. The CLO test results were confirmed by bacterial identification. WRPE-EtOH and WRPE-BuOH inhibited the growth of various bacteria and fungi, and in particular, they effectively killed H. pylori and eliminated the bacteria from the mouse stomach. The results indicate that WRPE-EtOH and WRPE-BuOH could be good candidates for the elimination of H. pylori.

Protective effects of N-acetyl-L-cysteine in human oligodendrocyte progenitor cells and restoration of motor function in neonatal rats with hypoxic-ischemic encephalopathy.

Objective. Since oligodendrocyte progenitor cells (OPCs) are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE), the present study was aimed at investigating the protective effects of N-acetyl-l-cysteine (NAC), a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.