Immunomodulatory and anti-inflammatory and anticancer activities of porphyran, a sulfated galactan.

Seaweeds are high in bioactive chemicals frequently used to treat human illnesses. Porphyran is a polysaccharide found in the red seaweeds of the genus Porphyra. Porphyran has been discovered to have immunomodulatory, anti-inflammatory activity, and anti-cancer effects via boosting immunity and targeting important apoptotic molecules, making them potential chemotherapeutic or chemopreventive drugs. Polysaccharide-mediated dynamic control of apoptosis and autophagy in cancer has been a viable treatment with low cytotoxicity with high efficacy. Thus, comprehending the influence of porphyran on human health and their molecular mechanisms would open up a new paradigm in cancer therapies. Also, the importance of apoptotic/autophagy modulating porphyran in cancer therapy has been highlighted as the future direction of improved nano-formulation for improved clinical efficacy. This review focuses on the current research into porphyran's anti-cancer efficacy and putative mechanisms of action through apoptosis and autophagy in various cancers, as well as its potential chemotherapeutic treatment in near future.

Partially Hydrolyzed Guar Gum Suppresses the Development of Sarcopenic Obesity.

Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber derived through controlled enzymatic hydrolysis of guar gum, a highly viscous galactomannan derived from the seeds of Cyamopsis tetragonoloba. Here, we examined the therapeutic potential of dietary supplementation with PHGG against sarcopenic obesity using Db/Db mice. Db/Db mice fed a normal diet alone or a fiber-free diet, or supplemented with a diet containing PHGG (5%), were examined. PHGG increased grip strength and the weight of skeletal muscles. PHGG increased the short-chain fatty acids (SCFAs) concentration in feces and sera. Concerning innate immunity, PHGG decreased the ratio of inflammatory cells, while increasing the ratio of anti-inflammatory cells in the small intestine. The present study demonstrated the preventive effect of PHGG on sarcopenic obesity. Changes in nutrient absorption might be involved through the promotion of an anti-inflammatory shift of innate immunity in the intestine accompanied by an increase in SCFA production by PHGG.

Polygalacto-fucopyranose biopolymer structured nanoparticle conjugate attenuates glucocorticoid-induced osteoporosis: An in vivo study.

Naturally occurring polysaccharide-structured nanoparticles have developed as promising materials for treatment of bone health disorders. Silver nanoparticle (ST-AgNP) structured from sulfated polygalacto-fucopyranose comprising of recurring structural entities of 2-SO3-α-(1 â†’ 3)-fucopyranose and 6-O-acetyl-ß-(1 â†’ 4)-galactopyranose isolated from marine macroalga Sargassum tenerrimum demonstrated potential activities associated with osteogenesis. Subsequent treatment with ST-AgNP, activity of alkaline phosphatase (63 mU/mg) was raised in osteoblast stem cells (human mesenchymal, hMSC) than that in control (30 mU/mg). Intense growth of mineralized nodule on the surface of hMSC was apparent following treatment with ST-AgNP. Increased population of bone morphogenic protein-2 (23%) and osteocalcin+ cells (50%) on M2 macrophages were apparent following treatment with ST-AgNP (0.25 mg/mL). Glucocorticoid-induced in vivo animal model studies of ST-AgNP exhibited significant recovery of serum biochemical parameters along with serum estradiol and parathyroid hormone compared to disease control. Disease-induced groups treated with ST-AgNP showed the disappearance of osteoporotic cavities in the trabecular bone. Following treatment with ST-AgNP, serum calcium and phosphorus contents were significantly recovered.

Structural elucidation and anti-diabetic osteoporotic activity of an arabinogalactan from Phellodendron chinense Schneid.

Phellodendron chinense Schneid. was widely used as a medicinal herb for the treatment of diabetic osteoporosis in China. In this study, an arabinogalactan, named as PPCP-1, was isolated from the bark of Phellodendron chinense Schneid., and purified by DEAE-cellulose DE52 and Sephacryl S-200 HR column chromatography. The structure of PPCP-1 was characterized as a repeating unit consisting of →3)-ß-d-Galp-(1→, →3,6)-ß-d-Galp-(1→, →5)-α-l-Araf-(1→, →4)-α-d-Glcp-(1→, →3)-α-d-Glcp-(1→, →4)-α-d-Manp-(1→ with branches of →5)-α-l-Araf-(1→, →3,5)-α-l-Araf-(1→ and terminal α-l-Araf. Pharmacologically, the oral administration of PPCP-1 preserved osteoporosis associated with hyperglycemia by inhibiting α-glucosidase activity, improving glucose tolerance, decreasing the accumulation of advanced glycation end products (AGEs), as well as down-regulating the expression of receptor for AGEs in tibias of streptozotocin-induced diabetic rats. Collectively, the present study suggested that the arabinogalactan PPCP-1 from Phellodendron chinense Schneid. might potentially be used as functional foods for bone health and/or developed for drug discovery for alleviating diabetic osteoporosis.

The structure elucidation of novel arabinogalactan LRP1-S2 against pancreatic cancer cells growth in vitro and in vivo.

The fruit of Lycium ruthenicum Murr is used as traditional medicine and functional food. Previously we reported that one RG-I pectin from this fruit might inhibit pancreatic cancer cells growth. We further hypothesized that there might be other type of polysaccharides in this fruit also have anti-tumor effect. Here, we showed novel structure of a homogeneous polysaccharide named LRP1-S2 from this fruit and its anti-pancreatic cancer effect. Structure analyses suggested that LRP1-S2 was a novel arabinogalactan with the molecular weight (Mw) of 17.0 kDa. Bioactivity test showed that LRP1-S2 might attenuate the proliferation of pancreatic cancer cells in vitro and in vivo without significant cytotoxicity to normal pancreatic HPDE6-C7 cells and LO2 liver cells. Mechanism study indicated that it might induce apoptosis of BxPC-3 by inactivating P38 MAPK/NF-κB and GSK-3ß/ß-Catenin signaling pathways. These results suggested that LRP1-S2 could be a potential anti-tumor leading compound for functional food and new drug development. CHEMICAL COMPOUNDS: arabinogalactan, pectin, galactan, arabinan, RN-1, HH1-1, LRP1-S2, LRP3-S1.

Structural characterization and hepatoprotective activity of a galactoglucan from Poria cocos.

To find the polysaccharide with hepatoprotective activity from Poria cocos and clarify its structure, a galactoglucan (PCP-1C) with a molecular weight of 17 kDa was purified from the Poria cocos sclerotium by column chromatography and activity evaluation in the present work. It was composed of galactose, glucose, mannose, and fucose in a molar percentage of 43.5: 24.4: 17.4: 14.6. Structural characterization showed that PCP-1C has a backbone consisted of 1,6-α-D-Galp, which branches composed of 1,3-ß-D-Glcp, 1,4-ß-D-Glcp, 1,6-ß-D-Glcp, T-ß-D-Glcp, T-α-D-Manp, T-α-L-Fucp and 1,3-α-L-Fucp. In vivo experiments found that PCP-1C can apparently improve the damage of liver tissue in CCl4-treated mice and relieve oxidative stress and inflammation. PCP-1C also reduced the expression of CAR and CYP2E1 in the liver. These findings indicated strong hepatoprotective effect of PCP-1C, which was attributed to the reduction of CCl4 metabolism via inhibiting the CAR/CYP2E1 signal pathway.

Fibers in pediatric functional gastrointestinal disorders. Practical considerations from clinical cases.

Introduction: Functional gastrointestinal disorders (FGIDs) are common in children and incur high direct and indirect social costs. Partially hydrolyzed guar gum (PHGG) is a natural and water-soluble dietary fiber that is derived from guar gum. It has been proposed as complementary therapy in pediatric FGIDs, especially in chronic functional constipation and irritable bowel syndrome.Areas covered: By focusing on four clinical cases, this article illustrates the use of PHGG fiber as sole supplement ingredient or as a formula component in orally- and tube-fed children suffering from malnutrition due to FGIDs, with or without special medical conditions such as neurological disability. The formula used was a whey peptide-based nutritionally complete formula containing PHGG as a source of soluble dietary fiber. It was offered under medical supervision and after full consideration of all feeding options.Expert opinion: Implementing appropriate feeding behaviors, adapted to age and potential comorbidities, is an essential requisite for therapeutic management of FGIDs. The use of a PHGG supplement or a nutritionally complete formula containing PHGG as a source of soluble dietary fiber can be helpful to manage pediatric FGIDs.

Preventive Effect of Depolymerized Sulfated Galactans from Eucheuma serra on Enterotoxigenic Escherichia coli-Caused Diarrhea via Modulating Intestinal Flora in Mice.

In this work, the preventive effect of depolymerized sulfated polysaccharides from Eucheuma serra (DESP) on bacterial diarrhea by regulating intestinal flora was investigated in vivo. Based on the enterotoxigenic Escherichia coli (ETEC)-infected mouse diarrhea model, DESP at doses ranging from 50 mg/kg to 200 mg/kg alleviated weight loss and decreased the diarrhea rate and diarrhea index. Serological tests showed that the levels of inflammation-related factors were effectively suppressed. Furthermore, the repaired intestinal mucosa was verified by morphology and pathological tissue section observations. Compared with the model group, the richness and diversity of the intestinal flora in the DESP group increased according to the 16S rRNA high-throughput sequencing of the gut microbiota. Specifically, Firmicutes and Actinobacteria increased, and Proteobacteria decreased after DESP administration. At the family level, DESP effectively improved the abundance of Lactobacillaceae, Bifidobacteriaceae, and Lachnospiraceae, while significantly inhibiting the growth of Enterobacteriaceae. Therefore, the antimicrobial diarrhea function of DESP may be related to the regulation of intestinal microbiota.

Comparison of the Effect of Ceratonia siliqua L. (Carob) Syrup and Vitamin E on Sperm Parameters, Oxidative Stress Index, and Sex Hormones in Infertile Men: a Randomized Controlled Trial.

Herbal products with an antioxidant capacity can boost male reproductive functions. The empiric use of Ceratonia siliqua (carob) for its antioxidant properties is common among infertile men in Iran and Turkey. The objective of this study is to investigate the effects of C. siliqua (carob) on semen parameters, oxidative stress markers, and pregnancy rate in a parallel randomized, controlled study. A total of 60 infertile men with oligozoospermia, asthenospermia, and teratospermia were recruited from April 2018 to March 2019. Participants were divided randomly into the following two groups: carob syrup twice a day or vitamin E 100 mg twice a day for 3 months. Semen analysis was performed and hormonal levels and stress oxidative markers were measured in each treatment arm after 3 months. The quality of semen parameters improved in the carob group compared with Vit E semen count (p = 0.04 Cohen's d = .51), morphology (p = 0.001 Cohen's d = .93) and motility parameters (p = 0.002 Cohen's d = .90) were significantly higher in the carob group. No significant difference can be detected in post-treatment hormonal parameters and oxidative markers between groups, except for total antioxidant capacity(TAC) which was higher after post-treatment in carob group. A significantly higher pregnancy rate was found among the carob group. The administration of carob may be an effective agent for the improvement of semen parameters, probably related both to its involvement in the changing of testosterone level and to its antioxidant properties. Nevertheless, additional studies to evaluate the optimal dose and duration of treatment are needed. The trial has been registered in the Iranian Registry of Clinical Trials (Registration number: IRCT20171209037794N1.

Tinospora cordifolia and arabinogalactan exert chemopreventive action during benzo(a)pyrene-induced pulmonary carcinogenesis: studies on ultrastructural, molecular, and biochemical alterations.

The aim of the present study was to unveil the chemopreventive potentials of aqueous Tinospora cordifolia stem extract and its active component viz. Arabinogalactan against Benzo(a)pyrene-induced pulmonary carcinogenesis. Animals were divided into six groups: (I) Control, (II) aqueous Tinospora cordifolia (200 mg/kg b.wt, p.o.), (III) arabinogalactan (7.5 mg/kg b.wt, p.o.), (IV) benzo(a)pyrene (50 mg/kg b.wt, i.p.) at second and fourth week of study, (V) benzo(a)pyrene + aqueous Tinospora cordifolia, and (VI) benzo(a)pyrene + arabinogalactan. The benzo(a)pyrene treatment resulted in severe alterations in the cellular arrangement and morphology of the alveolar tissue in benzo(a)pyrene group. However, benzo(a)pyrene + aqueous Tinospora cordifolia and benzo(a)pyrene + arabinogalactan groups revealed classical features of apoptosis including chromatin condensation and formation of apoptotic bodies. Furthermore, Fourier transform Infrared spectroscopy analysis showed disturbed phospholipid saturation and protein secondary structures in benzo(a)pyrene treated animals. Depletion in relative glycogen and enhancement in total nucleic acid content was observed in benzo(a)pyrene treated animals, and the same was found to be restored upon arabinogalactan and aqueous Tinospora cordifolia supplementation. Benzo(a)pyrene insult also upregulated the phase I carcinogen metabolizing enzymes and differentially modulated the phase II metabolizing enzymes during pulmonary carcinogenesis. Also, depleted (reduced glutathione) and increased lipid peroxidation levels were observed in benzo(a)pyrene treated animals, which was found to be normalized upon aqueous Tinospora cordifolia and arabinogalactan administration. Clastogenic damage inflicted by benzo(a)pyrene was also reversed in benzo(a)pyrene + aqueous Tinospora cordifolia and benzo(a)pyrene + arabinogalactan group. Thus, the present study infers that aqueous Tinospora cordifolia and arabinogalactan showed promising anticancer activity against lung tumorigenesis in terms of ultrastructural, biochemical, and biomolecular aspects.

Depolymerized sulfated galactans from Eucheuma serra ameliorate allergic response and intestinal flora in food allergic mouse model.

The ameliorative effect of depolymerized sulfated polysaccharides from Eucheuma serra (DESP) on ovalbumin (OVA)-caused induced food allergy was investigated in this work. Results showed that OVA stimulated the secretion of allergy-related cytokines (OVA-specific IgE, mMCP-1, IgA, TNF-α) and led to diarrhea, intestinal epithelial damage, and intestinal microflora dysbiosis in sensitized mice. After the administration of DESP, however, the anaphylactic symptoms (shortness of breath, hypothermia, diarrhea), along with the allergy-related cytokines, were effectively suppressed. Moreover, the reduced intestinal inflammation was discovered in the DESP-treated group. Additionally, 16S rRNA sequencing of fecal samples was performed, and gene count and α-diversity analysis revealed that DESP improved microbial community richness. Taxonomic composition analysis showed that DESP modulated the proportion of Firmicutes and Bacteroidetes/Proteobacteria. Particularly, DESP increased probiotics (Lactobacillaceae, Bifidobacteriaceae and Prevotellaceae) and decreased pathogenic bacteria (Helicobacteraceae and Desulfovibrionaceae). These findings, therefore, suggest that DESP may ameliorate food allergy through the regulation of intestinal microbiota.

Therapeutic Uses of Red Macroalgae.

Red Seaweed "Rhodophyta" are an important group of macroalgae that include approximately 7000 species. They are a rich source of structurally diverse bioactive constituents, including protein, sulfated polysaccharides, pigments, polyunsaturated fatty acids, vitamins, minerals, and phenolic compounds with nutritional, medical, and industrial importance. Polysaccharides are the main components in the cell wall of red algae and represent about 40-50% of the dry weight, which are extensively utilized in industry and pharmaceutical compounds, due to their thickening and gelling properties. The hydrocolloids galactans carrageenans and agars are the main red seaweed cell wall polysaccharides, which had broad-spectrum therapeutic characters. Generally, the chemical contents of seaweed are different according to the algal species, growth stage, environment, and external conditions, e.g., the temperature of the water, light intensity, nutrient concentrations in the ecosystem. Economically, they can be recommended as a substitute source for natural ingredients that contribute to a broad range of bioactivities like cancer therapy, anti-inflammatory agents, and acetylcholinesterase inhibitory. This review touches on the main points of the pharmaceutical applications of red seaweed, as well as the exploitation of their specific compounds and secondary metabolites with vital roles.

Pharmacological interventions for treating intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build-up of bile acids in the maternal blood. It has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been largely empiric. As ICP is an uncommon condition (incidence less than 2% a year), many trials have been small. Synthesis, including recent larger trials, will provide more evidence to guide clinical practice. This review is an update of a review first published in 2001 and last updated in 2013. OBJECTIVES: To assess the effects of pharmacological interventions to treat women with intrahepatic cholestasis of pregnancy, on maternal, fetal and neonatal outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials, including cluster-randomised trials and trials published in abstract form only, that compared any drug with placebo or no treatment, or two drug intervention strategies, for women with a clinical diagnosis of intrahepatic cholestasis of pregnancy. DATA COLLECTION AND ANALYSIS: The review authors independently assessed trials for eligibility and risks of bias. We independently extracted data and checked these for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 26 trials involving 2007 women. They were mostly at unclear to high risk of bias. They assessed nine different pharmacological interventions, resulting in 14 different comparisons. We judged two placebo-controlled trials of ursodeoxycholic acid (UDCA) in 715 women to be at low risk of bias. The ten different pharmacological interventions were: agents believed to detoxify bile acids (UCDA) and S-adenosylmethionine (SAMe); agents used to bind bile acids in the intestine (activated charcoal, guar gum, cholestyramine); Chinese herbal medicines (yinchenghao decoction (YCHD), salvia, Yiganling and Danxioling pill (DXLP)), and agents aimed to reduce bile acid production (dexamethasone) Compared with placebo, UDCA probably results in a small improvement in pruritus score measured on a 100 mm visual analogue scale (VAS) (mean difference (MD) -7.64 points, 95% confidence interval (CI) -9.69 to -5.60 points; 2 trials, 715 women; GRADE moderate certainty), where a score of zero indicates no itch and a score of 100 indicates severe itching. The evidence for fetal distress and stillbirth were uncertain, due to serious limitations in study design and imprecision (risk ratio (RR) 0.70, 95% CI 0.35 to 1.40; 6 trials, 944 women; RR 0.33, 95% CI 0.08 to 1.37; 6 trials, 955 women; GRADE very low certainty). We found very few differences for the other comparisons included in this review. There is insufficient evidence to indicate if SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with intrahepatic cholestasis of pregnancy. AUTHORS' CONCLUSIONS: When compared with placebo, UDCA administered to women with ICP probably shows a reduction in pruritus. However the size of the effect is small and for most pregnant women and clinicians, the reduction may fall below the minimum clinically worthwhile effect. The evidence was unclear for other adverse fetal outcomes, due to very low-certainty evidence. There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, YCHD, DXLP, Salvia, Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy. There are no trials of the efficacy of topical emollients. Further high-quality trials of other interventions are needed in order to identify effective treatments for maternal itching and preventing adverse perinatal outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA).

Chlorella vulgaris α-L-arabino-α-L-rhamno-α,ß-D-galactan structure and mechanisms of its anti-inflammatory and anti-remodelling effects.

Microalgal exopolysaccharides (EPSs) are given great attention due to their potential biotechnology applications. Purified C. vulgaris EPS was subjected to compositional and sugar linkage analyses, and partial acid hydrolysis. Hydrolysate separation by gel chromatography afforded oligosaccharide fractions. Both, EPS and oligomers were studied by NMR spectroscopy. Data suggest very complex highly branched α-L-arabino-α-L-rhamno-α,ß-D-galactan structure. Backbone repeating unit is formed by →2)-α-L-Rha (1 â†’ 3)-α-L-Rha(1 â†’ sequence, highly branched by long 1,6-linked α-D-Galp side chains, further branched at C2, C3 or C4 by α-L-Araf, α-D-Galf and ß-D-Galf residues. α-L-Araf form longer 1,2-linked chains branched at C3, C4 or C5. Galf residues are localized as terminal units predominantly in the ß configuration, while α-D-Galp and α-L-Araf may be partially O-methylated. Ex vivo biological assays showed increased interleukin-12 (IL-12) and interferon-gamma (INF-γ) levels corresponding to transforming growth factor beta (TGF-ß) decrease in guinea pig model experimental asthma. These facts point to the anti-remodelling effect of Chlorella EPS and suggest its possible application in the treatment of asthma and chronic obstructive pulmonary disorder.

Combined therapy: rifaximin-α and arabinogalactan with lactoferrin combination effectively prevents recurrences of symptomatic uncomplicated diverticular disease.

INTRODUCTION: Background: Diverticulosis is the most common finding in the GI tract. Nearly half of the people with diverticula experience symptomatic uncomplicated diverticular disease (SUDD). AIMS: The primary endpoints of our study were to assess the effectiveness of combined therapy with rifaximin-α and arabinogalactan-lactoferrin in symptom reduction and normalization of bowel movements. The secondary endpoints were an assessment of efficacy in SUDD recurrence prevention and patients' compliance to the combined therapy. METHODS: A retrospective observational survey study was performed in 2019 among physicians experienced in diverticular disease (DD) treatment in Poland. Patients with previous episodes of recurrences treated with combined therapy (cyclic rifaximin-α at least 400 mg b.i.d/7 days/every month and continuous arabinogalactan-lactoferrin supplementation 1 sachet daily) were assessed after 3 and 6 months regarding symptoms' resolution in the three-point scale. The patients' SUDD history, diagnostic methods, treatment, and results, as well as patients' compliance were evaluated. RESULTS: 281 patients met inclusion criteria, and were further evaluated (67.6% women, median age 65 years). After 6 months of combined treatment, there was a statistically significant reduction in the total severity score (median from 1.7 [max 3 points] to 0.26; P < 0.0001; sum from 8.5 [max 15 points] to 1.28; P < 0.0001) and improvement in each symptom score. Stool frequency statistically normalized in every group. As many as 31.7% had complete symptom resolution. Patients' compliance with the therapy was very good and good in 92.9% of cases. C onclusions and discussion: Combination therapy with cyclic rifaximin-α and continuous arabinogalactan combined with lactoferrin are effective in SUDD treatment in terms of symptom resolution, bowel movement normalization, prevention of recurrences with very good patient's compliance.

Partially hydrolyzed guar gum alleviates small intestinal mucosal damage after massive small bowel resection along with changes in the intestinal microbiota.

PURPOSE: Short bowel syndrome is associated with intestinal mucosal inflammation and microbial dysbiosis, leading to intractable complications. Partially hydrolyzed guar gum (PHGG) has trophic and anti-inflammatory effects on the intestine. We investigated whether PHGG ameliorates small intestinal mucosal damage and alters the intestinal microbiota using a rat small bowel resection (SBR) model. METHODS: Sprague Dawley rats were divided into sham operation (Sham), Sham/PHGG, SBR, and SBR/PHGG groups. On day 21, all rats were euthanized. To assess small intestinal mucosal damage, the degeneration rate was morphometrically evaluated and immunohistochemically examined using anti-CD45 antibodies. Analyses of fecal microbiota using 16S rRNA and short-chain fatty acid production were also performed. RESULTS: The mucosal degeneration rate was significantly higher in the SBR group than in the Sham or SBR/PHGG groups. The number of CD45-positive cells was significantly higher in the SBR group than in the Sham, Sham/PHGG, or SBR/PHGG groups. The relative abundance of family Lachnospiraceae was significantly higher in the SBR/PHGG group than in the SBR group. CONCLUSIONS: PHGG administration alleviated small intestinal mucosal damage which could be associated with modulation of the intestinal microbiota.

The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C in otitis media with effusion in children: a randomized controlled trial.

OBJECTIVE: To evaluate the ability of oral supplements with immune-stimulating molecules (Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C) to reduce the inflammation of the upper airway tract and improve the outcome of otitis media with effusion (OME) in children. PATIENTS AND METHODS: Randomized controlled trial. One-hundred ninety-eight children (CI 95%: 12-96 months) were divided into four groups. Group 1 (48 subjects) received 10 ml of oral supplements (OS) with immune-stimulating molecules for three months (20 days consecutively, then 10 days of suspension - the therapeutic scheme was repeated three times); Group 2 (54 children) underwent treatment with 10 ml of OS for 90 consecutive days; Group 3 (48 subjects) received 15 ml of OS for 45 consecutive days; a control group (48 children) underwent the standard treatment for rhinitis and OME. Outcome measures included otoscopy, tympanometry, fibroendoscopy, and the pure tone audiometry (PTA) at T0 (before treatment), T1 (45 days after treatment), and T2 (90 days after treatment). RESULTS: All children treated with OS showed a reduction of Upper Airway Infection (UAI) episodes and OME compared to the control group independent of the administration method and posology. The three groups treated with OS showed statistically significant differences between T0 and T2 for otoscopy, tympanometry, fibroendoscopy, and PTA. In Group 2, the otoscopy and the tympanometry scores improved at T1. Group 2 and 3 had better PTA results than Group 1. CONCLUSIONS: OS with immune-stimulating molecules should be considered as a supporting therapy in children affected by recurrent episodes of UAI associated with OME due to their capacity to improve the immune response and reduce the inflammatory phenomena. OS can improve the fibroendoscopic findings by restoring middle ear ventilation, in addition to their ability to reduce inflammation in the middle ear.

A whey/guar "preload" improves postprandial glycaemia and glycated haemoglobin levels in type 2 diabetes: A 12-week, single-blind, randomized, placebo-controlled trial.

AIMS: To evaluate the effects of 12 weeks of treatment with a whey/guar preload on gastric emptying, postprandial glycaemia and glycated haemoglobin (HbA1c) levels in people with type 2 diabetes (T2DM). MATERIALS AND METHODS: A total of 79 people with T2DM, managed on diet or metformin (HbA1c 49 ± 0.7 mmol/mol [6.6 ± 0.1%]), were randomized, in single-blind fashion, to receive 150 mL flavoured preloads, containing either 17 g whey protein plus 5 g guar (n = 37) or flavoured placebo (n = 42), 15 minutes before two meals, each day for 12 weeks. Blood glucose and gastric emptying (breath test) were measured before and after a mashed potato meal at baseline (without preload), and after the preload at the beginning (week 1) and end (week 12) of treatment. HbA1c levels, energy intake, weight and body composition were also evaluated. RESULTS: Gastric emptying was slower (P < 0.01) and postprandial blood glucose levels lower (P < 0.05) with the whey/guar preload compared to placebo preload, and the magnitude of reduction in glycaemia was related to the rate of gastric emptying at both week 1 (r = -0.54, P < 0.001) and week 12 (r = -0.54, P < 0.0001). At the end of treatment, there was a 1 mmol/mol [0.1%] reduction in HbA1c in the whey/guar group compared to the placebo group (49 ± 1.0 mmol/mol [6.6 ± 0.05%] vs. 50 ± 0.8 mmol/mol [6.7 ± 0.05%]; P < 0.05). There were no differences in energy intake, body weight, or lean or fat mass between the groups. CONCLUSIONS: In patients with well-controlled T2DM, 12 weeks' treatment with a low-dose whey/guar preload, taken twice daily before meals, had sustained effects of slowing gastric emptying and reducing postprandial blood glucose, which were associated with a modest reduction in HbA1c, without causing weight gain.

HH1-1, a novel Galectin-3 inhibitor, exerts anti-pancreatic cancer activity by blocking Galectin-3/EGFR/AKT/FOXO3 signaling pathway.

Pancreatic ductal adenocarcinoma is a highly malignant gastrointestinal tumor. Molecular targeting therapy for pancreatic cancer is still limited. High expressed Galectin-3 in pancreatic cancer is positively correlated with disease progression, indicating that Galectin-3 can be employed as a predictor of poor prognosis. From safflower, we isolated and purified a homogeneous polysaccharide, HH1-1, which could bind to and inhibit Galectin-3. HH1-1 could block the interaction between Galectin-3 and EGFR. Following HH1-1 treatment, the binding ability between EGFR and Galectin-3 was reduced by 245.28 folds. HH1-1 could suppress pancreatic cancer cell proliferation, arrest the cell cycle in S phase, induce cell apoptosis, inhibit angiogenesis and impede tumor cell migration and invasion. Moreover, HH1-1 affected the Galectin-3/EGFR/AKT/FOXO3 signaling pathway and possessed anti-pancreatic cancer activity in vitro and in vivo, especially in patient-derived xenografts. Further study suggested that HH1-1 had almost no toxicity both in vitro and in vivo. This adds new evidence to suggest that HH1-1 could be a promising therapeutic agent and support the pursuit of the Galectin-3 as a target in pancreatic cancer treatment.

Potential of two delivery systems for nisin topical application to dental plaque biofilms in dogs.

BACKGROUND: Periodontal disease (PD) is caused by the development of a microbial biofilm (dental plaque) in the periodontium, affecting approximately 80% of dogs. Several bacterial species present in the canine oral cavity can be implicated in the development of this disease, including Enterococcus spp. To decrease antibiotic administration, a possible control strategy for dog's enterococcal PD may involve the use of the antimicrobial peptide (AMP) nisin. Nisin's inhibitory activity was evaluated against a collection of previously characterized enterococci obtained from the oral cavity of dogs with PD (n = 20), as well as the potential of a guar-gum gel and a veterinary toothpaste as topical delivery systems for this AMP. The Minimum Inhibitory (MIC) and Bactericidal Concentrations (MBC) and the Minimum Biofilm Eradication (MBEC) and Inhibitory Concentrations (MBIC) were determined for nisin and for the supplemented guar-gum gel. For the supplemented veterinary toothpaste an agar-well diffusion assay was used to evaluate its inhibitory potential. RESULTS: Nisin was effective against all isolates. Independently of being or not incorporated in the guar-gum gel, its inhibitory activity on biofilms was higher, with MBIC (12.46 ± 5.16 and 13.60 ± 4.31 µg/mL, respectively) and MBEC values (21.87 ± 11.33 and 42.34 ± 16.61 µg/mL) being lower than MIC (24.61 ± 4.64 and 14.90 ± 4.10 µg/mL) and MBC (63.09 ± 13.22 and 66.63 ± 19.55 µg/mL) values. The supplemented toothpaste was also effective, showing inhibitory activity against 95% of the isolates. CONCLUSIONS: The inhibitory ability of nisin when incorporated in the two delivery systems was maintained or increased, demonstrating the potential of these supplemented vehicles to be applied to PD control in dogs.