Colon cancer prevention with walnuts.

PMID: 

Cancer Prev Res (Phila). 2019 Dec 9. Epub 2019 Dec 9. PMID: 31818852

Abstract Title: 

Colon cancer prevention with walnuts: A longitudinal study in mice from the perspective of a gut enterotype-like cluster.

Abstract: 

There is limited understanding of how walnut consumption inhibits the development of colorectal cancer(CRC). A possible mechanism may involve alterations to the gut microbiota. In this study, the effects of walnut on gut microbiota was tested in a mouse tumor bioassay using the colonotropic carcinogen, azoxymethane (AOM) added to the Total Western Diet (TWD). 16S rRNA pyrosequencing identified 3 enterotype-like clusters (E1, E2, E3) in this murine model. E1, E2 and E3 are associated with AOM exposure, walnut consumption and TWD diet, respectively. E2 and E3 showed distinct taxonomic and functional characteristics, while E1 represented an intermediate state. At the family level, E1 and E3 were both enriched with Bacteroidaceae, but driven by two different OTUs (OTU-2 for E1, OTU-4 for E3). E2 was overrepresented with Porphyromonadaceae and Lachnospiraceae, with OTU-3 (family Porphyromonadaceae) as the 'driver' OTU for this cluster. Functionally, E3 is overrepresented with genes of glycan biosynthesis and metabolism, xenobiotic metabolism and lipid metabolism. E2 is enriched with genes associated with cell motility, replication and repair, and amino acid metabolism. Longitudinally, E2 represents the gut microbial status of early life in these mice. In comparison with E1 and E3, E2 is associated with a moderate lower tumor burden (p=0.12). Our results suggest that walnuts may reduce the risk of CRC within a Western diet by altering the gut microbiota. Our findings provide further evidence that CRC risk is potentially modifiable by diet via alterations to the microbiota.

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Phloretin ameliorates hyperuricemia-induced chronic renal dysfunction.

PMID: 

Phytomedicine. 2020 Jan ;66:153111. Epub 2019 Oct 16. PMID: 31790902

Abstract Title: 

Phloretin ameliorates hyperuricemia-induced chronic renal dysfunction through inhibiting NLRP3 inflammasome and uric acid reabsorption.

Abstract: 

BACKGROUND: Hyperuricemia (HUA) is an important risk factor for renal diseases and contributes to renal fibrosis. It has been proved that phloretin has antioxidant and anti-inflammatory properties and could inhibit uric acid (UA) uptake in vitro. However, whether phloretin has a renal protective role in vivo remains unknown.PURPOSE: This study aims to evaluate the therapeutic effect of phloretin on HUA-induced renal injury in mice and to reveal its underlying mechanism.METHODS: Mice were induced hyperuricemic by oral gavage of adenine/potassium oxonate. The effects of phloretin on renal function, fibrosis, oxidative stress, inflammation, and UA metabolism in HUA mice were evaluated. The effect of phloretin on NLRP3 pathway was analyzed in human renal tubular cell lines (HK-2).RESULTS: HUA mice showed renal dysfunction with increased renal fibrosis, inflammation and mitochondrial stress. By contrast, phloretin reduced the level of serum blood urea nitrogen (BUN), urinary albumin to creatinine ratio (UACR), tubular necrosis, extracellular matrix (ECM) deposition and interstitial fibroblasts in HUA mice. The renal infiltration of inflammatory cells, cytokines such as NOD-like receptor family pyrin domain containing 3 (NLRP3) and interleukin-1β (IL-1β) release, mitochondrial reactive oxygen species (ROS) and morphological lesions in HUA mice also decreased. Furthermore, phloretin partly inhibited renal glucose transporter 9 (GLUT9) and promoted urinary UA excretion in HUA mice. In vitro, phloretin suppressed the NLPR3 pathway under LPSor UA stimulation in HK-2 cells.CONCLUSIONS: Phloretin could effectively attenuate UA-induced renal injury via co-inhibiting NLRP3 and UA reabsorption, and thus it might be a potential therapy to hyperuricemia-related renal diseases.

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Low-dose phloretin alleviates diabetic atherosclerosis through endothelial KLF2 restoration.

PMID: 

Biosci Biotechnol Biochem. 2019 Dec 3:1-9. Epub 2019 Dec 3. PMID: 31791197

Abstract Title: 

Low-dose phloretin alleviates diabetic atherosclerosis through endothelial KLF2 restoration.

Abstract: 

We investigated whether low-dose phloretin served as daily dietary supplements could ameliorate diabetic atherosclerosis and the role of kruppel-like factor 2 (KLF2). HUVECs cultured in high glucose medium were treated with different concentrations of phloretin and KLF2 mRNA, and protein level was detected. Diabetes was induced using streptozotocin inmice after which they were fed a high-cholesterol diet for 8 weeks. Diabetic mice injected with KLF2 shRNA-lentivirus or control virus were treated with 20 mg/kg phloretin. Glucose, lipid profile, aortic atheroma, and endothelial nitric oxide synthase (eNOS) expression were detected. Phloretin retained endothelial function by KLF2-eNOS activation under hyperglycemia. Low-dose phloretin helped with lipid metabolism, and blocked the acceleration of atherosclerosis in STZ-induced diabetic mice since the early stage, which was diminished by KLF2 knockdown. Low-dose phloretin exhibited athero-protective effect in diabeticmice dependent on KLF2 activation. This finding makes phloretin for diabetic atherosclerosis.

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Phloretin can be used in a potential combination therapy with metformin for the prevention and rescue of type 2 diabetes.

PMID: 

Food Funct. 2019 Dec 10. Epub 2019 Dec 10. PMID: 31821397

Abstract Title: 

Beneficial effects of combination therapy of phloretin and metformin in streptozotocin-induced diabetic rats and improved insulin sensitivity in vitro.

Abstract: 

The GLUT4 and PI3K/AKT signaling pathways are the key sensors of energy status and they regulate glucose and lipid metabolism. Phloretin activates the PI3K/AKT pathway by promoting GLUT4 translocation and expression, thereby improving glucose consumption and tolerance. As metformin can regulate glucose metabolism, we hypothesized that phloretin can amplify its gluco-regulatory effects. Male Sprague Dawley rats were fed with a high-fat and high-sugar diet for 8 weeks and injected with a low dose of streptozotocin to induce type 2 diabetes. The diabetic rats were randomized to receive phloretin (100 mg kg-1 d-1), metformin (250 mg kg-1 d-1), or phloretin + metformin via oral gavage for another 4 weeks. Random blood glucose, serum insulin, free fatty acid, total cholesterol, triglyceride, and low-density lipoprotein levels were detected in type 2 diabetic rats. Hematoxylin-eosin and Oil Red O staining were used to observe the pathological changes in the liver, pancreas, and adipose tissues of type 2 diabetic rats. The expression levels of IRS-1, PI3K, P-AKT, and GLUT4 in skeletal muscle were detected using western blotting. Phloretin plus metformin improved fasting blood glucose levels, glucose tolerance, and insulin sensitivity in type 2 diabetic rats. In addition, this combination reduced lipid accumulation, improved the pathological changes in the liver, pancreas, and adipose tissue, and increased IRS-1, PI3K, P-AKT, and GLUT4 expression in skeletal muscle and the liver of type 2 diabetic rats. Thus, phloretin can be used in a potential combination therapy with metformin for the prevention and rescue of type 2 diabetes.

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Daily nut consumption in the healthy diet pattern of adults could have positive effects on their cognitive function.

PMID: 

Nutr Hosp. 2019 Oct 17 ;36(5):1179-1188. PMID: 31475842

Abstract Title: 

[Nut consumption and cognitive function: a systematic review].

Abstract: 

Antioxidant-rich diet patterns could contribute to the prevention and treatment of early stages of dementia. Nuts have an appreciable antioxidant load and there is evidence of their positive effects on several chronic diseases incidence and death rates. Moreover, they are rich in polyunsaturated fatty acids, which might also play a positive role in neurogenesis. The aim of this systematic review was to summarize the evidence from studies related to the effects of nut consumption on cognitive function among adults. We conducted a systematic search of articles published in PubMed, Scopus and Web of Science. A total of 19 articles met the inclusion criteria (seven cross-sectional, four prospective cohorts and eight experimental); these were independently extracted and reviewed by two reviewers. The evidence from the cross-sectional and cohort studies was uncertain, due to the disparity of results and risk of bias. However, in most experimental studies a protective effect of nut consumption on some dimension of cognitive function was observed and the methodological quality of these studies was acceptable. In addition, the effects appear to be independent of nut type, amount of intake, age and baseline status of subjects. In summary, these results suggest that the inclusion of daily nut consumption in the healthy diet pattern of adults could have positive effects on their cognitive function. Nevertheless, more well-designed longitudinal and experimental studies are needed to provide strength to this suggestive evidence.

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Diets with a higher intake of nuts may be associated with a decreased risk of NAFLD.

PMID: 

BMJ Open. 2019 Sep 4 ;9(9):e028961. Epub 2019 Sep 4. PMID: 31488477

Abstract Title: 

Association between nut intake and non-alcoholic fatty liver disease risk: a retrospective case-control study in a sample of Chinese Han adults.

Abstract: 

OBJECTIVES: Nut consumption has been associated with a lower risk of type 2 diabetes, metabolic syndrome and insulin resistance. However, its effect on the risk of non-alcoholic fatty liver disease (NAFLD) is unknown. Therefore, we investigated the relationship between nut consumption and NAFLD risk.SETTING AND PARTICIPANTS: We conducted a retrospective case-control study including 534 patients diagnosed with NAFLD and 534 controls matched by sex and age (±5 years) from the Affiliated Nanping First Hospital of Fujian Medical University in China.MAIN OUTCOME MEASURES: Information on dietary intake was collected using a semiquantitative food frequency questionnaire and nut consumption was calculated. Nut consumption was categorised using quartiles based on the distribution of daily nut intake of the controls. Binary logistic regression models were used to estimate ORs and the 95% CIs for the association between nut consumption and NAFLD risk.RESULTS: After adjusting for potential confounding variables, nut consumption was not associated with NAFLD risk in the overall sample. When the fully adjusted model was stratified by sex, a significant inverse association was found between high nut consumption and NAFLD only among the men in the highest quartile (OR=0.43; 95% CI 0.26 to 0.71;0.01). The inverse association of nut consumption with NAFLD risk in men remained significant after controlling for other known or suspected risk factors for NAFLD.CONCLUSIONS: Diets with a higher intake of nuts may be associated with a decreased risk of NAFLD, particularly in men.

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Potential mechanisms mediating the protective effects of a peptide from walnut against hydrogen peroxide induced neurotoxicity in PC12 cells.

PMID: 

Food Funct. 2019 Jun 19 ;10(6):3491-3501. PMID: 31143910

Abstract Title: 

Potential mechanisms mediating the protective effects of a peptide from walnut (Juglans mandshurica Maxim.) against hydrogen peroxide induced neurotoxicity in PC12 cells.

Abstract: 

Amelioration of oxidative stress has been the main approach to improve neurodegenerative disorders. In the present study, a walnut peptide with a strong capacity of scavenging reactive oxygen species (ROS) was purified and identified as EVSGPGLSPN by SEC, RP-HPLC, and HPLC-MS/MS. Treatment with EVSGPGLSPN could significantly (P

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These findings support the concepts that stealth viruses can account for a spectrum of dysfunctional brain diseases and that some of these viruses may have arisen from live polio viral vaccines.

PMID: 

Pathobiology. 1996 ;64(2):64-6. PMID: 8888270

Abstract Title: 

Simian cytomegalovirus-related stealth virus isolated from the cerebrospinal fluid of a patient with bipolar psychosis and acute encephalopathy.

Abstract: 

A cytopathic 'stealth' virus was cultured from the cerebrospinal fluid of a patient with a bipolar psychotic disorder who developed a severe encephalopathy leading to a vegetative state. DNA sequencing of a polymerase chain reaction-amplified product from infected cultures has identified the virus as an African green monkey simian cytomegalovirus (SCMV)-related stealth virus. The virus is similar to the SCMV-related stealth virus isolated from a patient with chronic fatigue syndrome. The findings support the concepts that stealth viruses can account for a spectrum of dysfunctional brain diseases and that some of these viruses may have arisen from live polio viral vaccines.

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Deregulation of the immune system, influenced by specific agents such as infections, vaccinations, and silicone (breast implants), is implicated in chronic fatigue syndrome.

PMID: 

Ann N Y Acad Sci. 2009 Sep ;1173:600-9. PMID: 19758205

Abstract Title: 

Infection, vaccination, and autoantibodies in chronic fatigue syndrome, cause or coincidence?

Abstract: 

Chronic fatigue syndrome (CFS) is a heterogeneous syndrome of unknown etiology and physiopathology. CFS patients complain about disabling fatigue, depression, difficulty with memory, and concomitant skeletal and muscular pain. Interestingly enough, there is certain overlap between CFS symptoms, autoimmune rheumatic disease, and infectious diseases. Certain neuroendocrine-immune abnormalities have also been described, and autoantibodies commonly described in some autoimmune diseases have been found in CFS patients as well. An increasing number of autoantibodies, mainly directed against other nuclear cell components, have been illustrated. Likewise, an association between some infectious agents, antibody production, and later CFS onset has been reported. Similarly, vaccination is depicted as playing an important role in CFS onset. Recently, a case report pointed toward a causal association between silicone breast linkage, hepatitis B virus vaccination, and CFS onset in a previous healthy woman. Such findings suggest that there is a likely deregulation of the immune system influenced by specific agents (infections, vaccination, and products, such as silicone). Evidence suggests that CFS is a complex disease in which several risk factors might interact to cause its full expression. Thus, although different alterations have been found in CFS patients, undoubtedly the main feature is central nervous system involvement with immunological alterations. Therefore, a new term neuro-psycho-immunology must be quoted. New studies based on this concept are needed in order to investigate syndromes, such as CFS, in which immunological alterations are thought to be associated with concomitant psychological and health disturbances.

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