The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression.

BACKGROUND: Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions. OBJECTIVES: We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2. METHODS: ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung, and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro. RESULTS: OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation. CONCLUSIONS: OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of coronavirus disease 2019.

[EVALUATION OF PROTOCOLS FOR RUSH SUBCUTANEOUS IMMUNOTHERAPY WITH STANDARDIZED HOUSE DUST MITE EXTRACTS].

BACKGROUND: Widely accepted loading protocols for rush subcutaneous immunotherapy (rSCIT) have not been established. Our aim was to evaluate the loading protocols of rSCIT. METHODS: In the low initial dose group (33 patients), the initial dose of standardized house dust mite extract was 1 JAU or less. The target dose at the end of the rush build-up phase was 500 JAU. Next, the initial dose was increased to 10 JAU with the same target dose in the high initial dose group (18 patients). Furthermore, in the modified high initial dosage group (17 patients), the initial dose was 10 JAU but the target dose at the end of the rush phase was 300 JAU. Then, the maintenance dose of 500 JAU was administered at 9 or 10 days after rSCIT initiation. We retrospectively evaluated these protocols. RESULTS: A systemic reaction (SR) occurred in 28 out of 33 (84.8%) patients in the low initial dosage group and in 12 out of 18 (66.7%) patients in the high initial dosage group, on the other hand significantly reduced in 4 out of 17 (23.5%) patients in the modified high-dosage group. The amount of antigen reached 339.3±19.0 JAU in the low initial dosage group and 358.3±24.9 JAU in the high initial dosage group at the end of the rush phase, significantly increased 452.9±20.6 JAU in the modified high-dosage group at 9 or 10 days. CONCLUSION: In rSCIT using standardized house dust mite extract, lowering the target dose at the end of the rush phase and delaying the administration of the maintenance dose may reduce SR and increase the reached amount of antigen.

Oral administration of oyster (Crassostrea gigas) hydrolysates protects against wrinkle formation by regulating the MAPK pathway in UVB-irradiated hairless mice.

Chronic ultraviolet (UV) irradiation induces wrinkle formation. UV exposure increases reactive oxygen species (ROS) and upregulates the expression of matrix metalloproteinases (MMPs), which results in skin photoaging. Oyster (Crassostrea gigas), which is an abundant food resource in Asia and Europe, contains various sources of biological compounds and has several effects. Also, oyster hydrolysate (OH) has many biological activities. We investigated the inhibitory effects of OH on wrinkle formation in UVB-irradiated hairless mice. We induced UVB irradiation in hairless mice for 18 weeks and administered OH orally from the 9th week to the 18th week. We performed skin replicas and histological analyses in UVB-irradiated hairless mice dorsal skins. To determine the inhibitory mechanism of OH on wrinkle formation, we measured gene and protein expressions in dorsal skin using RT-qPCR and western blot analyses respectively. In our study, OH decreases wrinkle formation, epidermal thickness and collagen degradation in UVB-irradiated hairless mice. The gene expressions of MMPs were decreased and the gene expressions of collagen type I and TIMP-1 were increased in OH administered groups. Like gene expression tendencies, the protein expressions of MMPs were reduced and that of collagen type I was increased. Furthermore, the phosphorylation levels of ERK, JNK, and p38 were reduced in OH administered groups. We found that OH inhibits wrinkle formation, skin thickening, and collagen degradation by downregulating the MMP expression via the regulation of phosphorylation of MAPK. The results showed that OH significantly prevents UVB-induced photoaging in dorsal skin. Consistent with in vivo data, OH has potential as an anti-wrinkle agent.

Red Deer Umbilical Cord Lining Mesenchymal Stem Cell Extract Cream for Rejuvenation of the Face

Background: Aging is a multifactorial process that involves all components of the skin. Both intrinsic and extrinsic forces play a role in this aging process. A new patented protein mix derived from red deer umbilical cord lining stem cell conditioned media (Calecim® Multi Action Cream, CellResearch Corporation, Singapore) has been developed to improve the signs of aging. The extract is the conditioned media from umbilical cord lining mesenchymal stem cell culture in basal media and consists of a mixture, in specific proportions, of cytokines, growth factors, extracellular matrix proteins, amino acids, peptides, and other proteins. It has been developed to increase epidermal cell turnover and stimulate fibroblast function, reducing the appearance of pigmentation, fine lines, and redness, and to restore skin elasticity. Objective: The objective of this IRB-approved, prospective, randomized, double-blind, split-face, placebo-controlled clinical trial was to compare the efficacy of red deer mesenchymal stem cell extract (RCE) versus vehicle for facial rejuvenation. Methods: The trial involved 40 healthy subjects with moderate to severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical RCE cream and vehicle cream to the other half of the face. Treatment was continued for 3 months, and evaluations were performed in a double-blind fashion. Results: Both sides of the face achieved significant improvement. Blinded investigator assessments did not detect any statistically significant differences between the two halves of the face in terms of efficacy, safety, or tolerability. Subject evaluations demonstrated superiority of the active treatment side. Conclusion: Red deer umbilical cord lining mesenchymal stem cell extract was effective in rejuvenating the aging face as demonstrated by investigator and subject measures. J Drugs Dermatol. 2019;18(4):363-366.

Broncho-vaxom alleviates persistent allergic rhinitis in patients by improving Th1/Th2 cytokine balance of nasal mucosa.

BACKGROUND: Probiotics are mainly distributed in the mucosal system and have the ability to enhance mucosal barrier function and regulate immune responses. Broncho-Vaxom (BV), as a probiotic, has been applied to patients suffering from respiratory tract infections, but its potential effectiveness in allergic rhinitis (AR) has not been evaluated in human. This study aimed to investigate the clinical efficacy of BV in patients with persistent AR and to elucidate the underlying cellular mechanisms. METHODS: Sixty patients with AR were enrolled to this study and were randomly assigned to the BV group (n=30) and the placebo group (n=30). Changes of clinical symptoms and laboratory parameters of allergic inflammation were measured at baseline visit, immediately after BV treatment, four weeks, and eight weeks after the BV treatment. RESULTS: After BV treatment, medication score in the BV group was significantly decreased compared with placebo group, along with a significant drop of the total nasal symptom score and the individual nasal symptom scores (itching score: 23.72±5.32%; nasal rhinorrhea score: 18.59±4.83%; sneezing score: 23.08±4.98%). The levels of IL-4 and IL-13 in nasal lavage were diminished remarkably while the level of INF-γ was markedly increased in the BV group. This rendered a significant reduction of the ratio of IL-4/INF-γ. Moreover, a decrease of eosinophils in nasal smear was observed after BV treatment. The BV-induced favorable changes sustained for at least four to eight weeks post BV treatment. CONCLUSION: Oral administration of BV offers remarkable and sustained efficacy in alleviating AR symptoms and may be considered as an alternative therapeutic strategy for patients with persistent AR. BV acts by improving the overall mucosal immunity via restoring and maintaining the normal Th1/Th2 cytokine balance as an underlying cellular/signaling mechanism.

IMMUNEPOTENT CRP induces cell cycle arrest and caspase-independent regulated cell death in HeLa cells through reactive oxygen species production.

BACKGROUND: Regulated cell death (RCD) is a mechanism by which the cell activates its own machinery to self-destruct. RCD is important for the maintenance of tissue homeostasis and its deregulation is involved in diseases such as cervical cancer. IMMUNEPOTENT CRP (I-CRP) is a dialyzable bovine leukocyte extract that contains transfer factors and acts as an immunomodulator, and can be cytotoxic to cancer cell lines and reduce tumor burden in vivo. Although I-CRP has shown to improve or modulate immune response in inflammation, infectious diseases and cancer, its widespread use has been limited by the absence of conclusive data on the molecular mechanism of its action. METHODS: In this study we analyzed the mechanism by which I-CRP induces cytotoxicity in HeLa cells. We assessed cell viability, cell death, cell cycle, nuclear morphology and DNA integrity, caspase dependence and activity, mitochondrial membrane potential, and reactive oxygen species production. RESULTS: I-CRP diminishes cell viability in HeLa cells through a RCD pathway and induces cell cycle arrest in the G2/M phase. We show that the I-CRP induces caspase activation but cell death induction is independent of caspases, as observed by the use of a pan-caspase inhibitor, which blocked caspase activity but not cell death. Moreover, we show that I-CRP induces DNA alterations, loss of mitochondrial membrane potential, and production of reactive-oxygen species. Finally, pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, prevented both ROS generation and cell death induced by I-CRP. CONCLUSIONS: Our data indicate that I-CRP treatment induced cell cycle arrest in G2/M phase, mitochondrial damage, and ROS-mediated caspase-independent cell death in HeLa cells. This work opens the way to the elucidation of a more detailed cell death pathway that could potentially work in conjunction with caspase-dependent cell death induced by classical chemotherapies.

[Effects of bacterial lysates and all trans-retinoic acid on airway inflammation in asthmatic mice].

OBJECTIVE: To observe the effects of bacterial lysates (OM-85BV) and all trans-retinoic acid (ATRA) on airway inflammation in asthmatic mice, and to investigate the immunoregulatory mechanism of OM-85BV and ATRA for airway inflammation in asthmatic mice. METHODS: Forty female BALB/c mice were randomly divided into five groups: normal control, model, OM-85BV, ATRA, and OM-85BV+ATRA. A bronchial asthma model was established by intraperitoneal injection of ovalbumin (OVA) for sensitization and aerosol challenge in all mice except those in the normal control group. On days 25-34, before aerosol challenge, the model, OM-85BV, ATRA, and OM-85BV+ATRA groups were given normal saline, OM-85BV, ATRA, and OM-85BV+ATRA respectively by gavage. Normal saline was used instead for sensitization, challenge, and pretreatment before challenge in the normal control group. These mice were anesthetized and dissected at 24-48 hours after the final challenge. Bronchoalveolar lavage fluid (BALF) was collected from the right lung to measure the levels of interleukin-10 (IL-10) and interleukin-17 (IL-17) by ELISA. The left lung was collected to observe histopathological changes by hematoxylin-eosin staining. The relative expression of ROR-γT mRNA was measured by quantitative real-time PCR. RESULTS: Compared with the normal control group, the model group showed contraction of the bronchial cavity, increased bronchial secretions, and a large number of infiltrating inflammatory cells around the bronchi and alveolar walls, as well as a significantly reduced level of IL-10 (P<0.05) and significantly increased levels of IL-17 and ROR-γT mRNA (P<0.05). Compared with the model group, the OM-85BV, ATRA, and OM-85BV+ATRA groups showed a significant reduction in infiltrating inflammatory cells around the bronchi and alveolar walls; the OM-85BV group showed a significant increase in the level of IL-10 in BALF (P<0.05) and significant reductions in the levels of IL-17 and ROR-γT mRNA (P<0.05); the ATRA group showed significant reductions in the levels of IL-17 and ROR-γT mRNA (P<0.05). Compared with the OM-85BV group, the OM-85BV+ATRA group had significantly increased relative expression of ROR-γT mRNA (P<0.05). Compared with the ATRA group, the OM-85BV+ATRA group had significantly increased levels of IL-10 and IL-17 in BALF (P<0.05). CONCLUSIONS: Both OM-85BV and ATRA can reduce respiratory inflammation in asthmatic mice. However, a combination of the two drugs does not have a better effect than them used alone.

Wound healing potential of adipose tissue stem cell extract.

Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed was examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing.

Antitumor activity of a Rhodococcus sp. Lut0910 isolated from polluted soil.

The actinomycetes strain, lut0910, was isolated from polluted soil and identified as the Rhodococcus species with 99% similarity based on the sequence analysis of 16S recombinant DNA. The extract of this strain demonstrated in vivo and in vitro antitumor activity. The treatment of two human cancer cell lines, hepatocellular carcinoma HepG2 and cervical carcinoma Hela cells, with the lut0910 extract caused the delay in cell propagation in a dose-dependent manner with an IC50 of 73.39 and 33.09 µg/mL, respectively. Also, the oral administration of lut0910 extract to the mice with a solid tumor resulted in the inhibition of tumor growth in comparison with a placebo group. The thymus and spleen indexes were significantly increased in mice groups treated with the lut0910 extract. The histopathological changes of the tumor tissues showed that there were massive necrotic areas in the tumor tissues after treatment with different doses of the lut0910 extract. Our result would provide a new way and potent source for development of new anticancer agent from the polluted environment.

Phellinus linteus Grown on Germinated Brown Rice Increases Cetuximab Sensitivity of KRAS-Mutated Colon Cancer.

Colon cancer is one of the most common types of cancer, and it has recently become a leading cause of death worldwide. Among colon cancers, the v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated form is notorious for its non-druggable features. Cetuximab, a monoclonal antibody that binds to the epidermal growth factor receptor, has been introduced as an antitumor therapy; however, secondary resistance and side effects significantly limit its effective use in these cancers. In this study, we prepared Phellinuslinteus on germinated brown rice (PBR) extracts to increase the sensitivity of KRAS-mutated colon cancers to cetuximab. The combined treatment of PBR extract and cetuximab suppressed SW480 cell viability/proliferation, with the cells exhibiting altered cellular morphology and clonogenic potential. AnnexinV-fluorescein isothiocyanate/propidium iodide-stained flow cytometry and Western blotting were performed, and PBR extract combined with cetuximab treatment increased apoptosis of the SW480 cells and suppressed their KRAS protein expression. The potential of PBR as a synergistic anticancer agent was further investigated in a tumor-xenografted mouse model. Tumor growth was significantly suppressed with PBR extract and cetuximab co-treatment. In conclusion, PBR increased the sensitivity of KRAS-mutated colon cancer cells to cetuximab, which indicates the potential use of PBR as a medical food against colon cancer.

IN VIVO STUDIES AND STABILITY STUDY OF CLADOPHORA GLOMERATA EXTRACT AS A COSMETIC ACTIVE INGREDIENT.

Marine algae are widely used as cosmetics raw materials. Likewise, freshwater alga Cladophora glomerata may be a good source of fatty acids and others bioactive agents. The aims of this study was to find out if the addition of the extract from the freshwater C. glonerata affects the stability of prepared cosmetic emulsions and to investigate in vivo effects of the extract in cosmetic formulations on hydration and elasticity of human skin. Extract from the freshwater C. glonierata was obtained using supercritical fluid extraction (SFE). Two forms of O/W emulsions were prepared: placebo and emulsion containing 0.5% of Cladophora SFE extract. The stability of obtained emulsions was investigated by using Turbiscan Lab Expert. Emulsions were applied by .volunteers daily. Corneometer was used to evaluate skin hydration and cutometer to examine skin elasticity. Measurements were conducted at reference point (week 0) and after 1st, 2nd, 3rd and 4th week of application. The addition of Cladophora extract insignificantly affected stability of the emulsion. The extract from C. glomerata in the emulsion influenced the improvement of both skin hydration and its elasticity. Thus, freshwater C. glonierata extract prepared via SFE method may be considered as an effective cosmetic raw material used as a moisturizing and firming agent.

Macroalgal activity against multiple drug resistant Aeromonas hydrophila: A novel treatment study towards enhancement of fish growth performance.

OBJECTIVE: The aim of this study was to evaluate the efficiency of macroalgal extracts as antibacterial agent against multidrug-resistant (MDR) bacteria isolated from Nile tilapia (Oreochromis niloticus) as well as to enhance the fish growth performance by macroalgae diet application. METHODS: A total of 50 swabs were collected from the diseased organs of tilapia fish including gills, skin, spleen, intestine, liver, kidney and muscle. The isolated bacteria were identified and then confirmed by using VITEK 2. Eight macroalgal species were collected from Abu-Qir, Alexandria coast, Egypt. After determination of their biomass, three solvents were used to prepare algal extracts. The antibacterial activities of different macroalgal extracts were measured against MDR Aeromonas hydrophila 6 (MDRAH6) using well-diffusion method. The mechanism by which macroalgal extract affects MDR bacteria was conducted by using transmission electron microscope (TEM). To evaluate the safety of the promising algal extract, GC-MS was performed to detect the composition of S. vulgare extract. In addition, growth performance was measured as an application of algal extracts into fish feed. RESULTS: Between eight collected macroalgal species, Sargassum vulgare showed the highest biomass production (53.4 g m-2). In addition, its ethanolic extract showed the highest significant antibacterial activity with MIC value of 250 µg ml-1. TEM examination showed distinctive changes in the treated MDRAH6 cells including rupture of the cell wall, leakage of cytoplasmic contents, alterations in the cytoplasm density in addition to totally cell deformation. In addition, GC-MS analysis revealed eleven identified components in S. vulgare ethanolic extract, in which 9,12-octadecadienoyl chloride and hexadecanoic acid methyl ester were dominant (46.6 and 19.7 %, respectively). Furthermore, dietary replacement of fish meal with S. vulgare ethanolic extract significantly enhanced the growth performance and survival of Nile tilapia with a significant reduction in the total bacterial count. CONCLUSION: Ethanol extract of the brown macroalga S. vulgare could be a promising antibacterial and a new active agent against MDR A. hydrophila, which could be a major causative agent of Nile tilapia fish diseases. In addition, this study recommended S. vulgare as a natural and effective source to enhance the growth performance of Nile tilapia. In fact, isolation and examination of the individual antibacterial active compounds of the S. vulgar ethanolic extract are under investigation.

Japanese sake yeast supplementation improves the quality of sleep: a double-blind randomised controlled clinical trial.

Activation of adenosine A2a receptors in cerebral neurons induces sleep in various mammals. It was previously found that Japanese sake yeast enriched in adenosine analogues activates A2a receptors in vitro and induces sleep in mice. Here it is reported that sake yeast activated A2a receptors in a cultured human cell line and improved human sleep quality in a clinical trial. Sake yeast activated A2a receptors in HEK cells in a dose-dependent manner with an EC50 of 40 µg mL(-1), and the activation was attenuated almost completely by the A2a receptor antagonist ZM241385 with an IC50 of 73 nm. In a double-blind placebo-controlled crossover clinical study, 68 healthy participants ingested tablets containing either 500 mg of sake yeast powder or a placebo (cellulose) 1 h before sleep for 4 days. Electroencephalograms were recorded during sleep at home with a portable device for 4 week days. Electroencephalogram analyses revealed that sake yeast supplementation significantly (P = 0.03) increased delta power during the first cycle of slow-wave sleep by 110%, without changing other sleep parameters. Sake yeast supplementation also significantly increased growth hormone secretion in the urine on awakening by 137% from 3.17 ± 0.41 (placebo) to 4.33 ± 0.62 (sake yeast) pg mg(-1) creatinine (P = 0.03). Subjective sleepiness (P = 0.02) and fatigue (P = 0.06) in the morning were improved by sake yeast. Given these benefits and the absence of adverse effects during the study period, it was concluded that sake yeast supplementation is an effective and safe way to support daily high-quality, deep sleep.

Bacterial extract (OM-85) with human-equivalent doses does not inhibit the development of asthma in a murine model.

BACKGROUND: OM-85 is an immunostimulant bacterial lysate, which has been proven effective in reducing the number of lower airways infections. We investigated the efficacy of the bacterial lysate OM-85 in the primary prevention of a murine model of asthma. METHODS: In the first phase of our study the animals received doses of 0.5µg, 5µg and 50µg of OM-85 through gavage for five days (days -10 to -6 of the protocol), 10 days prior to starting the sensitisation with ovalbumin (OVA), in order to evaluate the results of dose-response protocols. A single dose (5µg) was then chosen in order to verify in detail the effect of OM-85 on the pulmonary allergic response. Total/differential cells count and cytokine levels (IL-4, IL-5, IL-13 and IFN-γ) from bronchoalveolar lavage fluid (BALF), OVA-specific IgE levels from serum, lung function and lung histopathological analysis were evaluated. RESULTS: OM-85 did not reduce pulmonary eosinophilic response, regardless of the dose used. In the phase protocol using 5µg/animal of OM-85, no difference was shown among the groups studied, including total cell and eosinophil counts in BALF, serum OVA-specific IgE, lung histopathologic findings and lung resistance. However, OM-85 decreased IL-5 and IL-13 levels in BALF. CONCLUSIONS: OM-85, administered in early life in mice in human-equivalent doses, does not inhibit the development of allergic pulmonary response in mice.

The cytoprotective effects of ethanol extract of Ecklonia cava against oxidative stress are associated with upregulation of Nrf2-mediated HO-1 and NQO-1 expression through activation of the MAPK pathway.

The aim of the present study was to examine the cytoprotective effect of Ecklonia cava against oxidative stress in C2C12 myoblasts. The ethanol extract of E. cava (EEEC) prevented hydrogen peroxide (H2O2)-induced inhibition of the growth of C2C12 myoblasts and exhibited scavenging activity against intracellular reactive oxygen species (ROS) induced by H2O2. EEEC treatment attenuated H2O2-induced comet tail formation and phospho-histone γH2A.X expression. Furthermore, EEEC treatment enhanced the level of the phosphorylated form of nuclear factor erythroid 2- related factor 2 (Nrf2) and its nuclear translocation, which was associated with the induction of heme oxygenase-1 (HO-1) and NADPH-quinone oxidoreductase 1 (NQO-1). Zinc protoporphyrin IX, a HO-1 competitive inhibitor, significantly abolished the protective effects of EEEC against H2O2-induced ROS generation and growth inhibition in C2C12 myoblasts. Transient transfection with Nrf2-specific small interfering RNA restored the elevated HO-1 and NQO-1 expression and the phosphorylation of Nrf2 to near normal levels. The EEEC treatment also induced the activation of mitogen-activated protein kinases (MAPKs), and specific inhibitors of MAPKs abolished upregulated HO-1 and NQO-1, as well as the phosphorylation of Nrf2. Taken together, these data suggest that EEEC attenuates oxidative stress by activating Nrf2-mediated HO-1 and inducing NQO-1 via the activation of MAPK signaling pathways.

Induction and treatment of anergy in murine leprosy.

Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial-specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG-inoculated and MLM-inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell-mediated immune response (CMI) that was temporary in the MLM-inoculated group and long-lasting in the BCG-inoculated group. DLE were prepared from the spleens of MLM- and BCG-inoculated mice at the peak of CMI. Independent MLM intradermally-inoculated groups were treated every other day with HLT-DLE, BCG-DLE or MLM-DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 10(6) splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy.

T regulatory cells in childhood asthma.

Asthma is a chronic disease of the airways, most commonly driven by immuno-inflammatory responses to ubiquitous airborne antigens. Epidemiological studies have shown that disease is initiated early in life when the immune and respiratory systems are functionally immature and less able to maintain homeostasis in the face of continuous antigen challenge. Here, we examine the cellular and molecular mechanisms that underlie initial aeroallergen sensitization and the ensuing regulation of secondary responses to inhaled allergens in the airway mucosa. In particular, we focus on how T-regulatory (Treg) cells influence early asthma initiation and the potential of Treg cells as therapeutic targets for drug development in asthma.

The administration of a polyvalent mechanical bacterial lysate in elderly patients with COPD results in serological signs of an efficient immune response associated with a reduced number of acute episodes.

The administration of a polyvalent mechanical bacterial lysate (PMBL) in elderly patients with COPD has been shown to reduce the number of exacerbation. This is largely related to the involvement of cells belonging to the innate and the adaptive immune system (including dendritic cells, granulocytes, T and B lymphocytes and NK cells) that actively cooperate inducing the production of specific opsonizing antibodies directed to the antigens of PMBL. We have evaluated the production of antibodies directed to respiratory and systemic pathogens in a group of elderly COPD patients, recruited in a clinical trial, ancillary to a larger multicenter double blind, placebo-controlled, parallel-designed clinical trial in which patients were randomized to daily receive either PMBL or placebo. The treated group not only experienced a reduced number of seroconversion, but also, better controlled the number of infectious episodes and COPD exacerbations. It was thus evident that the administration of PMBL resulted not only effective in inducing the secretion of specific antibodies, but also effective in reducing the infectious episodes trough the potentiation of the antibody-mediated arm of the immune response.

Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia.

Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4(+) T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4(+)CD25(+)FoxP3(+) regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3(+) Tregs from naive CD4(+)CD25(-)FoxP3(-) T cells by an interferon-γ-dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with a chaperone-rich cell lysate (CRCL) vaccine, leading to improved survival and long-lasting protection against leukemia. The combination of CRCL as a source of tumor-specific antigens and Th-1 lymphocytes as an adjuvant has the potential to stimulate efficient specific antitumor immunity while restraining Treg-induced suppression.

Composition characterization and clinical efficacy study of a salmon egg extract.

OBJECTIVE: There is an increasing demand for scientifically documented over-the-counter products on the cosmetic market. Salmon eggs are rich in proteins, vitamins and minerals with anti-oxidative and anti-inflammatory properties, as well as free amino acids and lipids documented to be beneficial for skin. Of the fatty acids, several are commonly used as skin penetration enhancers. The unique combination of active substances led us to study whether an extract from salmon eggs could serve as an ingredient for skin care. METHODS: We conducted a double-blinded, randomized clinical trial with 66 healthy female volunteers. Efficacy of the salmon egg extract was evaluated at concentrations of 1% and 5% in vehicle formulation, and responses after 7, 14, 28 and 56 days of treatment were compared with baseline. Composition of the extract was analysed to improve the understanding of the effects of the extract on skin. The salmon egg extract was safety-tested by repeat insult patch test. RESULTS: Treatment of facial skin with the salmon egg extract significantly improved all parameters investigated, wrinkles, pigmentation, redness, brightness and hydration and led to global improvement of the facial skin. Efficacy of the extract was dose dependent and time dependent. There were no adverse reactions noted during the course of the repeat insult patch test, demonstrating that the extract causes neither skin irritation nor sensitization. Furthermore, chemical analyses of the extract revealed the composition of a vast number of active substances, including unsaturated fatty acids, vitamins, proteins, minerals, DNA and RNA. CONCLUSION: The salmon egg extract serves as a skin care ingredient that significantly improves characteristics important for perception of skin ageing and health. The efficacy of the treatment is conceivably accounted for by the unique combination of numerous active substances present in the salmon egg extract.