The impact of a competitive event and the efficacy of a lactic acid bacteria-fermented soymilk extract on the gut microbiota and urinary metabolites of endurance athletes: An open-label pilot study.

Diet and exercise can alter the gut microbiota, but recent studies have assessed the impact of athletic competition on gut microbiota and host metabolites. We designed an open-label pilot study to investigate the effects of both official competition and a multi-strain lactic acid bacteria-fermented soymilk extract (LEX) on the gut microbiota in Japanese college endurance athletes. The analysis of fecal 16S rRNA metagenome and urinary metabolites was used to identify changes in gut microbiota composition and host metabolism. When the fecal microbiota were investigated before and after a race without using of a supplement (pre-observation period), there was an increase in the phylum Firmicutes and decrease in Bacteroidetes. However, no changes in these phyla were seen before and after a race in those who consumed LEX. Before and after LEX ingestion, changes in urinary metabolites included a significant reduction in yeast and fungal markers, neurotransmitters, and mitochondrial metabolites including the TCA cycle. There were several correlations between urinary metabolites and the composition of fecal microbiota. For example, the level of tricarballylic acid was positively correlated with the composition ratio of phylum Firmicutes (Pearson's r = 0.66; p < 0.01). The bacterial species Parabacteroides distasonis was also found to correlate moderately with several urinary metabolites. These findings suggest two possibilities. First, endurance athletes experience significant fluctuations in gut microbiota after a single competition. Second, LEX ingestion may improve yeast and fungal overgrowth in the gastrointestinal tract and enhancing mitochondrial metabolic function.

Indonesia-Based Study of the Clinical and Cost-Saving Benefits of Subcutaneous Allergen Immunotherapy for Children with Allergic Rhinitis in Private Practice.

BACKGROUND: Until now, the cost of allergy treatment in the insured public health care system and the non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. OBJECTIVE: To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in a non-insured self-financing private health care system. METHODS: A retrospective cohort study conducted from 2015 until 2020 that compared the clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1098 subjects. RESULTS: A decrease in sp-HDM-IgE level (kU/mL) from 20.5 + 8.75 kU/mL to 12.1 + 3.07 kU/mL was observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT, it costs IDR 21,753,062.7 per child, and for non-SCIT, it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT, it costs IDR 17,024,138.8, while with non-SCIT, it costs IDR 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT, it costs IDR 9,550,126.6, while with non-SCIT, it costs IDR 52,073,938.9. CONCLUSIONS: In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.

Acceptability of small-sized oblong tablets in comparison to syrup and mini-tablets in infants and toddlers: A randomized controlled trial.

OBJECTIVE: There is limited evidence for the acceptability of various drug formulations holding the potential to improve medicines administration to children. Suitable formulations need to meet the requirements of pediatric patients. Previous studies have demonstrated the acceptance of mini-tablets. Oblong tablets may carry more active ingredient content per unit than mini-tablets and could be an important alternative when the drug substance requires administration of higher doses. The primary objective was to demonstrate non-inferiority of acceptability of oblong tablets in comparison to 3 ml glucose syrup in children aged 1 to 5 years. Secondary objectives were investigation of acceptability, swallowability and palatability of mini-tablets, oblong tablets and glucose syrup in children between 1 and 5 years. METHODS: An open, randomized, single dose two-way cross-over design in two parallel study arms was applied. 280 children were stratified to one of five age groups and randomized to receiving one oblong tablet (2.5 × 6 mm) in comparison either to 3 ml glucose syrup or to three mini-tablets (2 × 2 mm). Acceptability and swallowability were assessed according to pre-defined evaluation criteria. The application of the formulations was video documented to evaluate the palatability. RESULTS: As primary objective, non-inferiority was observed regarding acceptability of the oblong tablet compared to syrup in all age groups (84.4% vs 80.1%, difference 4,29% points with 95% CI of -3.00%,11.57%). For swallowability, superiority of the oblong tablet compared to syrup could be shown (74.5% vs. 53.2%, difference 21.26% points, 95% CI of 11.29%, 31.23%). Regarding palatability, <10% of children demonstrated unpleasant reaction after intake of the oblong tablet or mini-tablets as graded by both raters, however, in contrast up to 40% of children after intake of syrup. CONCLUSION: Oblong tablets are a promising, safe alternative to liquid drug formulations and administration of multiple mini-tablets in children.

Evaluation of sensitization to the crude extract of Dermatophagoides farinae and its derived allergens, Der f 2 and Zen 1, in dogs with atopic dermatitis in Southern Brazil.

BACKGROUND: Atopic dermatitis is associated with the production of IgE antibodies against environmental allergens and allergens of the house dust miteDermatophagoides farinae are frequently implicated in the disease. OBJECTIVES: We aimed to observe the allergen-specific IgE against crudeD. farinae, Der f 2 and Zen 1 in dogs with atopic dermatitis and report if these dogs are in contact with material that could shelter mite allergens. METHODS: 100 dogs with clinical diagnosis of atopic dermatitis were included after exclusion of other forms of pruritic skin disease and dogs that already received specific or non-specific immunotherapy. These dogs were of different breeds and ages and they were presented at a veterinary teaching hospital and a private service of veterinary dermatology, both located in Curitiba, Southern Brazil. At the time of anamnesis, some questions were applied to know the possibility of these dogs having had contact with furniture and textile material which could shelter house dust mites. Sera samples were obtained and further analyzed by ELISA assay to measure serum IgE levels against these allergens with an established cut-off of 0.200 IgE optical density. RESULTS: The allergen-specific IgE positivity against crudeD. farinae (92 %) and Zen 1 (77 %) was higher than Der f 2 (56 %). There was a correlation in sensitization to crude D. farinae and Zen 1 that was not observed between crude D. farinae and Der f 2 and Der f 2 and Zen 1. The sensitization to D. farinae and its allergens was associated with an unrestricted exposition to furniture and textile material. CONCLUSION & CLINICAL RELEVANCE: dogs with atopic dermatitis are frequently sensitized to D. farinae and its allergens, Der f 2 and Zen 1, may be considered major allergens in these dogs. Zen 1 may be the main allergen responsible for the sensitization to crude D. farinae.

The effect of oral low molecular weight liquid hyaluronic acid combination with glucosamine and chondroitin on knee osteoarthritis patients with mild knee pain: An 8-week randomized double-blind placebo-controlled trial.

BACKGROUND: The popularity of dietary supplements for knee osteoarthritis (OA) management is on the rise; however, their effects are still debated. METHODS: This study aimed to investigate the effect of an oral low molecular weight liquid hyaluronic acid supplement in the treatment of knee OA patients with mild knee pain (visual analogue scale [VAS] ≤ 3) in Taiwan population. This was a randomized, double-blind, placebo-controlled study. Forty-seven subjects were enrolled and randomly allocated to either the A+HA or the placebo groups. The subjects were required to drink a bottle contained 20 mL of A+HA or placebo daily throughout an 8-week study period. The efficacy was assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the 36-item Short Form Survey (SF-36). RESULTS: At Week 8, significant reductions from baseline in the WOMAC pain (-2.6 ±â€Š1.68, P < .0001), stiffness (-1.2 ±â€Š1.50, P = .007), physical function (-5.8 ±â€Š4.39, P < .0001), and total (-9.4 ±â€Š5.82, P < .0001) scores were observed in the A+HA group but not in the placebo group. Significant differences in the mean change of WOMAC scores from baseline at Week 8 between groups were detected (P < .01). At Week 8, the A+HA group also showed significant improvements in SF-36 physical functioning (2.7 ±â€Š3.10, P = .001) and bodily pain (0.7 ±â€Š1.50, P < .05) domains. Although the A+HA group had a higher increase in the SF-36 total score than the placebo group but the difference was not statistically significant (2.1 ±â€Š12.75 vs 0.3 ±â€Š19.66, P = .12). CONCLUSIONS: Oral administration of low molecular weight liquid HA appeared to be effective for knee OA patients with mild knee pain (VAS ≤ 3) in the relief of knee OA symptoms, particularly in pain and physical function.Clinical Trial Registration: NCT04352322.

Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by an impaired skin barrier and intense itchiness, which decreases the individual's quality of life. No fully effective therapeutic agents have prevailed for AD due to an insufficient grasp of the complex etiology. Ellagic acid (EA), a natural compound, has anti-inflammatory properties in chronic diseases. The effects of EA on AD have not yet been explored. The present study investigated the effects of EA on TNF-α/IFN-γ-stimulated HaCaT keratinocytes and house dust mite-induced AD-like skin lesions in NC/Nga mice. Treatment with EA suppressed inflammatory responses in keratinocytes by regulating critical inflammatory signaling pathways, such as mitogen-activated protein kinases and signal transducers and activators of transcription. In vivo studies using a DfE-induced AD mouse model showed the effects of EA administration through ameliorated skin lesions via decremented histological inflammatory reactions. These results suggest that EA could be a potential therapeutic alternative for the treatment of AD by inhibiting inflammatory signaling pathways.

Use of the imazapic herbicide applied alone or tank mix with imazapyr as growth regulator of lawns

Successive mowing are the major maintenance costs of lawns. Thus, both the expenditure with mowing and the visual and physiological aspect of the lawn have led to the search for alternatives to mechanical management. Thus, this work aimed to study the effects of different rates of imazapic herbicide applied alone or combined with imazapyr as a growth regulator of Bahiagrass (Paspalum notatum) and St. Augustine grass (Stenotaphrum secundatum). The experimental design was a randomized block with four replicates, and the treatments consisted of six rates of imazapic herbicide (35; 70; 105; 140; 175 and 210 g a.i. ha-1) for both species, three rates of imazapic + imazapyr in tank mix (15.57 + 5.25; 23.625 + 7.875; 32.5 + 10.5 g a.i. ha-1) for Bahiagrass and four rates of imazapic + imazapyr mixture (7.875 + 2.625; 15.57 + 5.25; 23.625 + 7.875; 32.5 + 10.5 g a.i. ha-1) for St. Augustine grass. The effect of the treatments was evaluated by observing visible injury symptoms, canopy height, height and number of inflorescences and total dry matter of clippings. Applications of imazapic alone or combined with imazapyr were effective in reducing plant height, number and height of inflorescences and total amount of dry matter of clippings produced by Bahiagrass plants. Imazapic provided satisfactory control of St. Augustine growth, but its utilization caused an increase in the number of inflorescences present in the lawns.

Applications of Mouse Models to the Study of Food Allergy.

Mouse models of allergic disease offer numerous advantages when compared to the models of other animals. However, selection of appropriate mouse models is critical to advance the field of food allergy by revealing mechanisms of allergy and for testing novel therapeutic approaches. All current mouse models for food allergy have weaknesses that may limit their applicability to human disease. Aspects such as the genetic predisposition to allergy or tolerance from the strain of mouse used, allergen dose, route of exposure (oral, intranasal, intraperitoneal, or epicutaneous), damage of the epithelial barrier, use of adjuvants, food matrix effects, or composition of the microbiota should be considered prior to the selection of a specific murine model and contemplated according to the intended purpose of the study. This chapter reviews our current knowledge on the application of mouse models to food allergy research and the variables that may influence the successful development of each type of model.

Methods for Experimental Allergen Immunotherapy: Subcutaneous and Sublingual Desensitization in Mouse Models of Allergic Asthma.

Allergic asthma is characterized by airway hyperresponsiveness, remodeling, and reversible airway obstruction. This is associated with an eosinophilic inflammation of the airways, caused by inhaled allergens such as house dust mite or grass pollen. The inhaled allergens trigger a type-2 inflammatory response with the involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high immunoglobulin E (IgE) antibody production by B cells and mucus production by airway epithelial cells. As a consequence of the IgE production, subsequent allergen reexposure results in a classic allergic response with distinct early and late phases, both resulting in bronchoconstriction and shortness of breath. Allergen-specific immunotherapy (AIT) is the only treatment that is capable of modifying the immunological process underlying allergic responses including allergic asthma. Both subcutaneous AIT (SCIT) as well as sublingual AIT (SLIT) have shown clinical efficacy in long-term suppression of the allergic response. Although AIT treatments are very successful for rhinitis, application in asthma is hampered by variable efficacy, long duration of treatment, and risk of severe side effects. A more profound understanding of the mechanisms by which AIT induces tolerance to allergens in sensitized individuals is needed to be able to improve its efficacy. Mouse models have been very valuable in preclinical research for characterizing the mechanisms of desensitization in AIT and evaluating novel approaches to improve its efficacy. Here, we present a rapid and reproducible mouse model for allergen-specific immunotherapy. In this model, mice are sensitized with two injections of allergen adsorbed to aluminum hydroxide, followed by subcutaneous injections (SCIT) or sublingual administrations (SLIT) of allergen extracts as an immunotherapy treatment. Finally, mice are challenged by intranasal allergen administrations. We will also describe the protocols as well as the most important readout parameters for the measurements of invasive lung function, serum immunoglobulin levels, isolation of bronchoalveolar lavage fluid (BALF), and preparation of cytospin slides. Moreover, we describe how to perform ex vivo restimulation of lung single-cell suspensions with allergens, flow cytometry for identification of relevant immune cell populations, and ELISAs and Luminex assays for assessment of the cytokine concentrations in BALF and lung tissue.

Study on the clinical mechanism of Tong-Xie-An-Chang Decoction in the treatment of diarrheal irritable bowel syndrome based on single-cell sequencing technology.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology. METHODS/DESIGN: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals. DISCUSSION: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.

Influence of Nigerian Jelly Ear Culinary-Medicinal Mushroom, Auricularia auricula-judae (Agaricomycetes), on Humoral and Cellular Immunity.

The fruiting body of Auricularia auricula-judae has received attention in folk medicine due to its possible medicinal values. Therefore, this study evaluated the immunomodulatory effects of the hot aqueous extract (AAAJ) and the ß-D-glucan-rich polysaccharide fraction of A. auricula-judae (BGPA) on specific and nonspecific humoral and cell mediated immune responses in immunocompetent and immunosuppressed mice. Oral supplementation with AAAJ or BGPA (100, 200, or 400 mg/kg) produced significantly high titers of total OVA specific or TT specific IgG1 and IgG2a compared with the levels in untreated control. Oral administration of AAAJ or BGPA (100, 200, or 400 mg/kg) evoked a significant increase in carbon clearance at all doses, indicating stimulation of the reticuloendothelial system, and potentiated the delayed-type hypersensitivity reaction induced by sheep red blood cells (SRBC) compared with the untreated mice. Total lymphocyte count, neutrophil count, and lymphocytes count increased significantly (P < 0.05) at all doses, following acute administration of AAAJ or BGPA (100, 200, or 400 mg/kg), showing increased protection toward cyclophosphamide induced myelosuppression compared with the untreated negative control group. In the hemolytic complement assay, AAAJ and BGPA at all doses significantly (P < 0.05) inhibited the hemolytic activity of the complement proteins on the sensitized SRBC. The present study reveals that the extract holds promise as an immunomodulatory agent and strengthens the rationale for its use in traditional medicine.

Efficacy and safety of Huaier granules combined with chemotherapy for gastric cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Huaier granules, the aqueous product of Huaier (Trametes robiniophila Murr.) extract, are a broad-spectrum anti-tumor drug and have been widely used for the treatment of gastric cancer (GC). The aim of this study is to systematically investigate the efficacy and safety of Huaier granules combined with chemotherapy in the treatment of GC. METHODS: Three English databases and four Chinese databases will be searched from its inception to July 2020. Two methodological trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.2 and stata 14.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by Cochrane X and I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger's test. The quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether Huaier granules combined with chemotherapy is an effective intervention for patient with GC. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/9BVJD.

CD122-targetted IL-2 signals cause acute and selective apoptosis of B cells in Peyer's Patches.

Interleukin-2 (IL-2) has both pro- and anti-inflammatory properties that have been harnessed clinically and that are used experimentally to modulate leukocyte subsets in vivo. In mice, the bioavailability and half-life of IL-2 in vivo can be increased by complexing recombinant IL-2 with different clones of anti-IL-2 monoclonal antibodies that differentially target the cytokine to cells expressing different kinds of IL-2 receptors. While the impacts of systemic IL-2: anti-IL-2 antibody complex (IL-2C) administration are well-defined in the spleen and peripheral lymph nodes, how immune cells in the gut and gut-associated lymphoid tissues respond to IL-2C is not well characterized. Here, we analyze how major leukocyte populations in these tissues respond to IL-2C. We find that IL-2C targeting cells expressing IL-2 receptor beta cause an acute decrease in cellularity of Peyer's Patches while cell numbers in the lamina propria and intraepithelial lymphocytes are unaffected. Cell contraction in Peyer's Patches is associated with the apoptosis of multiple B cell subsets. Our results are important to consider for understanding off-target impacts of IL-2C regimes in experimental models and for considering how IL-2 may contribute to the etiology or severity of gut-associated conditions such as Crohn's Disease.

Activity of Antioxidant Defense Enzymes in Rats with Experimental Allergic Encephalomyelitis.

We studied activities of antioxidant system enzymes in tissues of rats with experimental allergic encephalomyelitis. It was shown that the development of pathology is accompanied by deformation of the neurons and axonal degeneration, intensification of free radical oxidation, exhaustion of the reduced glutathione pool, and multidirectional changes in activities of antioxidant enzymes in rat tissues. The observed imbalance in the antioxidant defense system can be associated with excessive glutathione utilization in the glutathione transferase reaction and different severity of the pathological process in the brain and spinal cord. The received data necessitate the search for compounds that can prevent inhibition of antioxidant system components in order to analyze the possibility of their use in the treatment of multiple sclerosis.

Involvement of Bone Marrow Multipotent Stromal Cells in the Processes Presumably Provoking Vascular Calcification.

During serial transplantation of bone marrow derived from young and aged donor CBA mice to 5-month-old recipients, the counts of multipotent stromal cells (MSC) in transplants from young donors assessed at each passage surpassed those of aged donors by 3.2, 7.8, 3.0, and 2.2 times attesting to the age-related decrease of active pool of bone marrow MSC. The medullary curettage in mouse femur increased the total number of MSC and the number of osteogenic MSC both in the contralateral femur and in the bone marrow transplants attesting to spread of the effects of osteogenic factors after bone injury onto the bone tissue of the body even if this tissue if not topographically related to the skeleton. Combined and simultaneous administration of antigenic complex of S. typhimurium (or LPS) with BMP-2 markedly increased the count of osteogenic medullary MSC by 3.6 or 4.6 times in comparison with intact control or by 2.1 and 2.7 times in comparison with administration of BMP-2 alone, which probably resulted from enlargement of the pool of osteogenesis-inducible MSC due to inflammation. Addition of BMP-2 to the culture of splenic stromal cells where osteogenesis does not occur under normal conditions provoked appearance of MSC colonies with alkaline phosphatase activity attesting to involvement of inducible osteogenic MSC in vascular calcification. It can be hypothesized that the reaction to the age-related changes in the bone tissue and osteoporosis is similar to the reaction to bone marrow injury and includes initiation of systemic inflammation and elevation of blood BMP-2, both of which are prerequisite for vascular calcification.

Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial.

Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract AndosanTM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the AndosanTM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based AndosanTM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.

Development of Sponge Microspicule Cream as a Transdermal Delivery System for Protein and Growth Factors from Deer Antler Velvet Extract.

Sponge spicules are needle-like structures and used for dermabrasive treatment of the skin. This research aimed to develop an effective delivery system by using sponge spicules for enhancing skin permeation of bioactive proteins and growth factors from deer antler velvet (DAV). DAV was extracted by sonication and bioactivity studies were evaluated. The size of microspicules (MSs) was reduced and mixed with DAV extract cream. In vitro skin permeation was analyzed by using bovine serum albumin-fluorescein isothiocyanate conjugate (BSA-FITC) as a model macromolecular compound. For in vivo study, DAV extract formulations were applied on the skin of healthy humans, and effects were evaluated. Results showed that DAV extract containing proteins and growth factors increased the proliferation and migration of skin fibroblast cells. This extract was homogeneously mixed with spicule cream. Without blending, MS was 11.89 µm wide and 176.77 µm long; blending time exhibited short and broken MSs (MBs) for short blending (30 s) and fine powder (MF) for long blending (10 min). MS cream showed the highest permeation of BSA-FITC through the skin (2.26-fold enhancement), but it resulted in skin irritation. Therefore, MB cream that increased the permeation of BSA-FITC by 1.94-fold was not significantly different from MS formulations chosen for in vivo study. Applying DAV-containing MB cream on the skin for 14 d decreased the melanin content and erythema value but increased elasticity and hydration. Therefore, the MB-containing cream can enhance the macromolecule delivery through the skin, improve the skin properties, and avoid skin irritation.

The efficacy and safety of two commercial house dust mite extracts for allergic rhinitis: a head-to-head study.

BACKGROUND: Several studies have demonstrated the efficacy of house dust mite (HDM) immunotherapy in allergic rhinitis (AR). We aimed to compare the efficacy and safety of 2 commercial HDM extracts in a Chinese AR population. METHODS: This was an open-label study. HDM-associated AR patients were randomized into Dermatophagoides pteronyssinus (Dp) extracts (Alutard SQ; ALK, Hørsholm, Denmark) and Dp/Dermatophagoides farinae (Df) extracts (NovoHelisen Depot [NHD]; Allergopharma, Reinbek, Germany) groups. All patients received subcutaneous injections for 1 year, and were followed every 3 months during that 1-year period. Symptom score, medication score, and adverse reactions were recorded. The primary endpoint was the total combined symptom and medication score (CSMS) during the efficacy evaluation period. Blood samples were taken for specific immunoglobulin E (IgE), IgG4, and IgE-blocking factor tests at baseline and after the 1-year treatment. RESULTS: A total of 230 AR patients were randomized; 29 patients dropped out. Analysis of the primary endpoint demonstrated significant reductions in CSMS of 1.8 vs 3.1 (p < 0.001) in the Alutard group and 1.8 vs 3.3 (p < 0.001) in the NHD group compared with baseline. The 2 groups presented equal effectiveness with regard to CSMS, symptom score, and medication score (p > 0.05). The treatment was well tolerated in both groups; 17 (14.8%) patients experienced systemic reactions (SRs) in the Alutard group and 13 (11.3%) in the NHD group. The rates of SRs showed no difference in the 2 groups (p > 0.05), and no anaphylaxis occurred. IgG4 and IgE-blocking factor to Dp and Df were increased significantly in both groups after the 1-year treatment. CONCLUSION: Our study confirmed the equal efficacy and safety profile of both commercial extracts in HDM-associated AR patients.

Dose Effects of Orally Administered Spirulina Suspension on Colonic Microbiota in Healthy Mice.

Oral supplemented nutraceuticals derived from food sources are surmised to improve the human health through interaction with the gastrointestinal bacteria. However, the lack of fundamental quality control and authoritative consensus (e.g., formulation, route of administration, dose, and dosage regimen) of these non-medical yet bioactive compounds are one of the main practical issues resulting in inconsistent individual responsiveness and confounded clinical outcomes of consuming nutraceuticals. Herein, we studied the dose effects of widely used food supplement, microalgae spirulina (Arthrospira platensis), on the colonic microbiota and physiological responses in healthy male Balb/c mice. Based on the analysis of 16s rDNA sequencing, compared to the saline-treated group, oral administration of spirulina once daily for 24 consecutive days altered the diversity, structure, and composition of colonic microbial community at the genus level. More importantly, the abundance of microbial taxa was markedly differentiated at the low (1.5 g/kg) and high (3.0 g/kg) dose of spirulina, among which the relative abundance of Clostridium XIVa, Desulfovibrio, Eubacterium, Barnesiella, Bacteroides, and Flavonifractor were modulated at various degrees. Evaluation of serum biomarkers in mice at the end of spirulina intervention showed reduced the oxidative stress and the blood lipid levels and increased the level of appetite controlling hormone leptin in a dose-response manner, which exhibited the significant correlation with differentially abundant microbiota taxa in the cecum. These findings provide direct evidences of dose-related modulation of gut microbiota and physiological states by spirulina, engendering its future mechanistic investigation of spirulina as potential sources of prebiotics for beneficial health effects via the interaction with gut microbiota.

Preventive effect of purgative manna on neonatal jaundice: A double blind randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Cotoneaster nummularioides Pojark manna (Shir-e-Khesht) is popular in Persian medicine. Different effects of some Cotoneaster species manna include antibacterial, antioxidant, anticancer, and hepatoprotective effects, as well as bilirubin serum levels reduction. Cotoneaster species manna is used in many parts of Iran as a laxative and accelerates the passage of meconium. Neonatal jaundice has relatively costly and sometimes invasive therapeutic interventions, which its prevention from becoming severe cases can be a priority in neonatal medicine. AIM OF THE STUDY: The aim of this study was to evaluate the effectiveness of an herbal product (Purgative Manna, native to Iran and Asian countries) in preventing severe cases of jaundice and reducing total bilirubin levels in neonates. MATERIALS AND METHODS: This randomized double-blind controlled clinical trial included full-term babies. Four hundred and forty-five (445) eligible neonates were assigned to two groups using the block balanced randomization method; 222 neonates received the Purgative Manna product as drops, and 223 neonates received placebo drops. The neonates received a dose of 5 drops per kilogram of neonatal weight (divided into three doses per day) for three days. The treatment period was three days, and a 24-h (three times) examination was performed to measure the initial outcome of the trial (i.e., the total serum bilirubin level). The secondary outcomes of this trial were the need for hospitalization due to jaundice and/or phototherapy from 4 to 14 days after birth, the frequency of defecation within 24 h, and the triple complications of diarrhoea, dehydration symptoms, and abdominal colic. RESULTS: In this study, 220 neonates in the Purgative Manna product group and 222 neonates in the placebo group completed their interventions within the predicted period of the study. At the end of study, the total bilirubin level in the Purgative Manna treated group was significantly lower than that of the placebo group. The difference between the mean total bilirubin levels of the two groups was approximately 2.1 mg/dl on the third day after treatment, with an effect size of 0.79 (95% CI: 0.06-0.98). The relative risk for reducing the need for hospitalization or phototherapy in the group treated with Purgative Manna drops was 0.26, compared with the placebo group. The risk of occurrence of severe jaundice or phototherapy in the Purgative Manna group was 75% lower than that of the placebo group. The median frequency of defecation in the intervention group at three time intervals in the first, second and third days after treatment was 1-2 times more than that of the comparison group (p < 0.001). CONCLUSIONS: Meanwhile, considering the fact that one in every eight neonates who used the product avoided having a severe and high-risk case of jaundice or the need for phototherapy intervention (even through an exchange transfusion), the use of Purgative Manna drops can be recommended; however, further study is necessary.