The accumulation of misfolded α-synuclein in dopamine (DA) neurons is believed to be of major importance in the pathogenesis of Parkinson's disease (PD). Animal models of PD, based on viral-vector-mediated over-expression of α-synuclein, have been developed and show evidence of dopaminergic toxicity …

Inhibitory effects of trehalose liposomes (DMTre) composed of 30mol% l-α-dimyristoylphosphatidylcholine (DMPC) and 70mol% trehalose surfactants on the growth of lymphoblastic leukemia (MOLT-4) cells in vitro and therapeutic effects of DMTre for xenograft mice model of carcinoma in vivo were examined …

Neural Regen Res, Official publication of Publishing House of Neural Regeneration Research China Association of Rehabilitation Medicine,China

Fight sugar with sugar? A new study in mice suggests it might work.

BACKGROUND Previous studies indicated that both Plantago major and Aloe vera have anti-inflammatory, tissue regeneration, antioxidant, and immune-stimulatory effects. It is assumed that a mixture of these two herbal medicines may provide a potent material in treatment of skin wound injuries. Therefore, in this study we investigated the effects of Plantago major ...

Fucus vesiculosus L., known as bladderwrack, belongs to the brown seaweeds, which are widely distributed throughout northern Russia, Atlantic shores of Europe, the Baltic Sea, Greenland, the Azores, the Canary Islands, and shores of the Pacific Ocean. Fucoidan is a major fucose-rich sulfated polysaccharide found in Fucus (F.) vesiculosus. The pharmacokinetic profiling of active compounds is essential for drug development and approval. The aim of the study was to evaluate the pharmacokinetics and tissue distribution of fucoidan in rats after a single-dose oral administration. Fucoidan was isolated from F. vesiculosus. The method of measuring anti-activated factor X (anti-Xa) activity by amidolytic assay was used to analyze the plasma and tissue concentrations of fucoidan. The tissue distribution of fucoidan after intragastric administration to the rats was characterized, and it exhibited considerable heterogeneity. Fucoidan preferentially accumulates in the kidneys (AUC0–t = 10.74 µg·h/g; Cmax = 1.23 µg/g after 5 h), spleen (AUC0–t = 6.89 µg·h/g; Cmax = 0.78 µg/g after 3 h), and liver (AUC0–t = 3.26 µg·h/g; Cmax = 0.53 µg/g after 2 h) and shows a relatively long absorption time and extended circulation in the blood, with a mean residence time (MRT) = 6.79 h. The outcome of this study provides additional scientific data for traditional use of fucoidan-containing plants and offers tangible support for the continued development of new effective pharmaceuticals using fucoidan.

Trehalose is widely used as a sweetener, humectant, and stabilizer, but is ubiquitously degraded by the enzyme trehalase expressed in a broad variety of organisms. The stability of the new trehalose analogues lentztrehaloses A, B, and C in microbial and mammalian cell cultures and their pharmacokinetics in mice were analyzed to evaluate their potential as successors of trehalose. Among the 12 species of microbes and 2 cancer cell lines tested, 7 digested trehalose, whereas no definitive digestion of the lentztrehaloses was observed in any of them. When orally administered to mice (0.5 g/kg), trehalose was not clearly detected in blood and urine and only slightly detected in feces. However, lentztrehaloses were detected in blood at >1 μg/mL over several hours and were eventually excreted in feces and urine. These results indicate that lentztrehaloses may potentially replace trehalose as nonperishable materials and drug candidates with better bioavailabilities.

Hyperlipidemia is associated with increased risk of the development of cardiovascular diseases. Although a great deal of attention has been paid to th…

Background Acute radiation-induced proctitis (ARP) is the most common side effect following radiotherapy for malignant pelvic disease. This study evaluated the efficacy of Aloe vera ointment in prevention of ARP. Methods Forty-two patients receiving external-beam radiotherapy (RT) for pelvic malignancies were randomized to receive either Aloe vera 3% or placebo topical ointment during radiotherapy for 6 weeks. These patients were evaluated based on the severity (grade 0–4) of the following symptoms weekly: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. RTOG acute toxicity criteria and psychosocial status of the patients were also recorded weekly. Lifestyle impact of the symptoms, and quantitative measurement of C-reactive protein (CRP), an indicator of systemic inflammation, were also measured. Results The results of present study demonstrated a significant preventive effect for Aloe vera in occurrence of symptom index for diarrhea (p

Background: Exercise and nutrition are two basic foundations in the control of increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in diabetes disease. The aim of the present study was to review the interactional effects of endurance training and aloe vera gel on ALT and AST levels in ...

Random-pattern skin flaps are commonly used and valuable tools in reconstructive surgery, however, post-operative random skin flap necrosis remains a major and common complication. Previous studies have suggested that activating autophagy, a major pathway for degradation of intracellular waste, may improve flap survival. In this study, we investigated whether trehalose, a novel and potent autophagy activator, improves random skin flap viability. Our results demonstrated that trehalose significantly improves viability, augments blood flow, and decreases tissue edema. Furthermore, we found that trehalose leads to increased angiogenesis, decreased apoptosis, and reduced oxidative stress. Using immunohistochestry and western blot, we demonstrated that trehalose augments autophagy, and that inhibition of autophagy augmentation using 3MA significantly blunted the aforementioned benefits of trehalose therapy. Mechanistically, we showed that trehalose’s autophagy augmentation is mediated by activation and nuclear translocation of TFEB, which may be due to inhibition of Akt and activation of the AMPK-SKP2-CARM1 signaling pathway. Altogether, our results established that trehalose is a potent agent capable for significantly increasing random-pattern skin flap survival by augmenting autophagy and subsequently promoting angiogenesis, reducing oxidative stress, and inhibiting cell death.

Obesity is an escalating global pandemic posing a serious threat to human health. The intervention therapy using weight-reducing drugs, accompanied by lifestyle modification, is a strategy for the treatment of obesity. In the present study, we explored the role of fucoidan, a seaweed compound, on high-fat diet (HFD)-induced obesity in mice. We found that fucoidan treatment significantly reduced the body fat and caused redistribution of visceral and subcutaneous fat in HFD-fed mice. Meanwhile, fucoidan treatment inhibited adipocyte hypertrophy and inflammation in adipose tissue. Collectively, these results suggest that fucoidan may be a promising treatment for obesity and obesity-induced complications.

Inhibitory effects of trehalose liposomes (DMTre) composed of 30mol% l-α-dimyristoylphosphatidylcholine (DMPC) and 70mol% trehalose surfactants on the growth of lymphoblastic leukemia (MOLT-4) cells in vitro and therapeutic effects of DMTre for xenograft mice model of carcinoma in vivo were examined …

Cornea acts as a structural barrier and protects the eye from environmental stresses. Inflammation in ocular surface causes discomfort and visual dist…

This paper contains a review of the history, natural occurrence, human consumption, metabolism, manufacture, and the results of eight standardized animal safety studies using trehalose. Trehalose (alpha,alpha-trehalose) is a naturally occurring sugar containing two D-glucose units in an alpha,alpha- …

Fucoidan, a sulfated polysaccharide present in brown seaweed, has demonstrated anticancer activity in lung, breast, liver and colon cells. The insulin-like growth factor (IGF) signaling pathway regulates growth in HT-29 cells through the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Ras/Raf/extracellular signal-regulated kinase (ERK) pathways. The aim of the present study was to investigate whether fucoidan downregulates the IGF-IR signaling pathway in HT-29 human colon cancer cells. Fucoidan treatment (0-1,000 µg/ml) was administered for 24 h in HT-29 cells. First, we investigated IRS-1/PI3K/AKT pathway-related protein expression levels following treatment with fucoidan (0-500 µg/ml) using western blot analysis. Fucoidan significantly inhibited the expression of IGF-IR, PTEN, PI3K and AKT as well as their phosphorylated forms (p-IRS-1, p-PI3K and p-AKT). Next, we investigated the effects of fucoidan on Ras/Raf/ERK pathway‑related protein expression levels in HT-29 cells. Fucoidan significantly inhibited the expression of IGF-IR, Shc, Ras, SOS, Raf and MEK. HT-29 cells were then incubated in the presence of fucoidan (0 or 250 µg/ml), and IGF-I (10 nM) was added for 0 to 60 min. Immunoprecipitation (IP) experiments showed that fucoidan inhibited IGF-I-induced phosphorylation of IGF-IR, PI3K, Shc (IP, IGF-IR), and phosphorylated IRS-1 and PI3K (IP, IRS-1) compared to the control group. Western blot analysis showed that fucoidan inhibited the expression of IGF-I-induced p-IGF-IR/IGF-IR and p-AKT/AKT, but not p-ERK/ERK. In conclusion, the inhibition of cell viability by fucoidan in HT-29 cells may be due to the downregulation of IGF-IR signaling through the main IRS-1/PI3K/AKT pathway. Fucoidan also partially impacted Ras/Raf signaling in the Ras/Raf/ERK pathway. Therefore, we suggest that fucoidan may be a suitable candidate chemopreventive agent in HT-29 colon cancer cells.

BACKGROUND: The use of herbal and synthetic compounds can be effective in improving the areas and repair of tissues that have been affected during the processes like what happens in ulcerative colitis (UC) as a common inflammatory disorder. According to the beneficial effects of aloe vera, in this study, we aimed to assess the therapeutic effects of oral aloe vera gel on acetic acid-induced colitis in rats by histopathological and molecular analysis of Bax, and BCL-2 genes expression (using RT-PCR technique) in colon tissue samples. METHODS: This experimental study comprised 32 adult male Sprague Dawley rats weighting  220±20 g that were randomly divided into four groups as follows. The control group (healthy rats), colitis group in which UC was induced by transrectal administration of 3% acetic acid with no treatment, oral form of sulfasalazine group in which UC was induced by transrectal administration of 3% acetic acid, then was treated by oral administration of sulfasalazine 500 mg/kg body weight, and the fourth group which received oral form of aloe vera gel (200 mg/kg) for 21 days, respectively after induction of UC. Then, the therapeutic effects of treatment groups were compared with the control group and the colitis group with no treatment, by the assessment of histopathological and molecular changes in the colon tissues of rats on the 7 th , 14 th , and 21 st days. Finally, the collected data were analyzed using statistical tests. RESULTS: Histologically, aloe vera gel treatment could reduce and heal colon tissue damages in induced colitis. Also, this gel reduced apoptosis in rat’s colon with acetic acid-induced colitis, which showed in significantly decreased in Bax mRNA expression and significantly increased BCL-2 mRNA expression compared with the colitis group with no treatment. CONCLUSION:  Aloe vera gel has a significant effect on the treatment of UC in rat because of the beneficial effect that was found from aloe vera such as decreasing the severity of colitis as evidenced by histopathological findings, and with respect to apoptosis and gene expression that were related to wound healing process, and suppression of the elevation of Bax mRNA with the upregulation of Bcl-2, which can be considered effective in the treatment of UC.

Our study identifies TFEB as a master regulator of TAMs in breast cancer. TFEB controls TAM gene expression and function through multiple autophagy/lysosome-dependent and independent pathways. Therefore, pharmacological activation of TFEB would be a promising therapeutic approach to improve the effi …

Neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, Huntington's disease and others are due to accumulation of abnormal proteins which fold improperly and impair neuronal function. Accumulation of these proteins could be achieved by several mechanisms including mutation, overpr …

Click here to subscribe - https://www.glutenfreesociety.org/wxrn What are The Best Natural & Non Toxic Sweeteners? Some of the best natural sweeteners to use instead of sugar, aspartame (Nutrasweet), sucralose (Splenda), etc are listed below, but be careful not to overdo these either. Remember that too much natural sugar can also be detrimental. 1. Eat real fruit when it is in season 2. Honey - make sure it is naturally sourced and organic. Many brands of honey are laced with corn syrup. 3. Maple - pure organic 4. Organic Dates 5. Stevia 6. Monk Fruit 7. Sugar Alcohol (xylitol derived from birch) If you want a more in depth look on the topic of natural sweeteners, toxic sweeteners, and alternatives, check out this video: https://www.youtube.com/watch?v=v4BWY-4ptzg To connect with Dr. Osborne visit: On the web: https://drpeterosborne.com/ Facebook: https://www.facebook.com/DoctorPeterO... Pinterest: https://www.pinterest.com/docosborne/ Instagram: https://www.instagram.com/drosborne Twitter: https://twitter.com/glutenology *These statements have not been evaluated by the Food and Drug Administration. This video is not intended to diagnose, treat, cure or prevent any disease. It is strictly intended for educational purposes only. Additionally, this information is not intended to replace the advice of your physician. Dr. Osborne is not a medical doctor. He does not treat or diagnose disease. He offers nutritional support to people seeking an alternative from traditional medicine. Dr. Osborne is licensed with the Pastoral Medical Association.

Nutraceuticals are gaining importance owing to their potential applications in numerous sectors including food and feed industries. Among the emerging nutraceuticals, d-tagatose occupies a significan...

Insulin is an important therapeutic protein for the treatment of diabetes, but it is unstable and aggregates upon exposure to environmental stressors encountered during storage and transport. To prevent degradation of the protein in this manner and retain as much in vivo bioactivity as possible, a well-defined insulin–trehalose glycopolymer conjugate was synthesized. To accomplish this, a strategy was employed to site-specifically modify insulin with a polymerization initiator at a particular conjugation site; this also facilitated purification and characterization. Lysine of the B chain was preferentially modified by conducting the reaction at high pH, taking advantage of its higher nucleophilicity than the N-terminal amines. Trehalose monomer was polymerized directly from this macroinitiator to form a well-defined conjugate. Bioactivity of the site-specific conjugate was shown to be higher compared to the nonspecific conjugate and the same as the analogous site-specific poly(ethylene glycol) (PEG) conjugate, as confirmed by the insulin tolerance test (ITT) in mice. The conjugated trehalose glycopolymer also stabilized insulin to heat as measured by high-performance liquid chromatography (HPLC).

The objective of this study was to investigate the effect of dietary supplementation with the disaccharides trehalose and cellobiose on antioxidant activity in rumen fluid, blood, and milk of dairy cows. Nine Holstein dairy cows housed in a free-stall barn were divided into 3 groups, with each group …

Is Splenda really a food, or a highly toxic chemical?

As a continuous research for the discovery of trehalose-based anti-invasive agents, we developed a convenient synthetic approach for the preparation of 6,6'-dideoxy-6,6'-bis(acylamino)-α,α-D-trehaloses. A series of trehalose-based amides were prepared through the trityl protection of the two primary …

The present study demonstrated that fucoidan could inhibit the in vitro progression of oral squamous cell carcinoma (OSCC) cells by mediating the level of circFLNA. CircFLNA effects on signaling path...

The proposed mechanisms of the protective effect of FO against diabetes. Fucoidan ameliorates pancreatic β-cell damage and the impaired insulin synthesis by activating Sirt-1-mediated processes under...