PMID: 

Reprod Toxicol. 2013 Apr ;36:104-16. Epub 2013 Jan 25. PMID: 23453003

Abstract Title: 

Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

Abstract: 

Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures.

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PMID: 

J Clin Invest. 2010 May ;120(5):1603-16. Epub 2010 Apr 26. PMID: 20424322

Abstract Title: 

Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation.

Abstract: 

The folate pathway plays a crucial role in the regeneration and repair of the adult CNS after injury. Here, we have shown in rodents that such repair occurs at least in part through DNA methylation. In animals with combined spinal cord and sciatic nerve injury, folate-mediated CNS axon regeneration was found to depend on injury-related induction of the high-affinity folate receptor 1 (Folr1). The activity of folate was dependent on its activation by the enzyme dihydrofolate reductase (Dhfr) and a functional methylation cycle. The effect of folate on the regeneration of afferent spinal neurons was biphasic and dose dependent and correlated closely over its dose range with global and gene-specific DNA methylation and with expression of both the folate receptor Folr1 and the de novo DNA methyltransferases. These data implicate an epigenetic mechanism in CNS repair. Folic acid and possibly other nontoxic dietary methyl donors may therefore be useful in clinical interventions to promote brain and spinal cord healing. If indeed the benefit of folate is mediated by epigenetic mechanisms that promote endogenous axonal regeneration, this provides possible avenues for new pharmacologic approaches to treating CNS injuries.

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PMID: 

Mol Neurobiol. 2020 Jan 10. Epub 2020 Jan 10. PMID: 31919777

Abstract Title: 

Ancestral Folate Promotes Neuronal Regeneration in Serial Generations of Progeny.

Abstract: 

Folate supplementation in F0 mating rodents increases regeneration of injured spinal axons in vivo in 4 or more generations of progeny (F1-F4) in the absence of interval folate administration to the progeny. Transmission of the enhanced regeneration phenotype to untreated progeny parallels axonal growth in neuron culture after in vivo folate administration to the F0 ancestors alone, in correlation with differential patterns of genomic DNA methylation and RNA transcription in treated lineages. Enhanced axonal regeneration phenotypes are observed with diverse folate preparations and routes of administration, in outbred and inbred rodent strains, and in two rodent genera comprising rats and mice, and are reversed in F4-F5 progeny by pretreatment with DNA demethylating agents prior to phenotyping. Uniform transmission of the enhanced regeneration phenotype to progeny together with differential patterns of DNA methylation and RNA expression is consistent with a non-Mendelian mechanism. The capacity of an essential nutritional co-factor to induce a beneficial transgenerational phenotype in untreated offspring carries broad implications for the diagnosis, prevention, and treatment of inborn and acquired disorders.

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PMID: 

Biomed Pharmacother. 2019 Sep ;117:109200. Epub 2019 Jul 8. PMID: 31387194

Abstract Title: 

Protective effects of Bee pollen extract on the Caco-2 intestinal barrier dysfunctions induced by dextran sulfate sodium.

Abstract: 

Bee pollen (BP) is a natural medicine from the hive with various potential health-promoting benefits, but until now there is no study to determine its protective roles in inflammatory bowel disease (IBD). The aim of this study was to reveal the in vitro gastrointestinal protective effects of BP against IBD using molecular and metabolic methods. Dextran sulfate sodium (DSS) challenged Caco-2 cell monolayers were applied to mimic intestinal epithelial cell dysfunctions and metabolic disorders. The pretreatment with BP extract rich in polyphenols ameliorated DSS-induced cell viability losses. It also exerted protective effects against intestinal barrier impairment by strengthening epithelial integrity and tight junction losses induced by DSS. BP up-regulated anti-oxidant (NQO1, Txnrd1, Nrf2) and down-regulated inflammatory (TNF-α and IL-6) mRNA expressions, in accompany with MAPK signaling inhibition. Furthermore, metabolomics analysis based on UPLC-Q-TOF/MS revealed that BP, and DSS treated Caco-2 cells have different metabolomic profiles, with significant changes on key metabolites involved in glycerophospholipid metabolism. Our results showed that BP has great therapeutic potential throughout the early stages of DSS-induced colitis.

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U.S. health officials find a strong link between early instances of childhood trauma and adult chronic diseases ranging from heart disease and asthma to kidney disease and depression

PMID: 

J Investig Clin Dent. 2019 May ;10(2):e12393. Epub 2019 Jan 20. PMID: 30663271

Abstract Title: 

Effect of local probiotic (Lactobacillus reuteri) vs systemic antibiotic therapy as an adjunct to non-surgical periodontal treatment in chronic periodontitis.

Abstract: 

AIM: The aim of the present study was to assess and compare the clinical efficacy of local probiotic Lactobacillus reuteri (L. reuteri) and systemic antibiotics as adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis (CP).METHODS: Thirty systemically-healthy participants (15 probiotic and 15 antibiotic), clinically diagnosed with CP, were enrolled. All patients underwent SRP. Adjunctive probiotics were administered twice daily for 3 months, whereas a combination of amoxicillin and metronidazole were given three times daily for 7 days.RESULTS: Intragroup analysis showed statistically-significant improvement in all clinical parameters: plaque index, bleeding on probing, periodontal pocket depth, and clinical attachment level gain at each follow-up visit. However, intergroup comparison of clinical periodontal parameters did not show statistical significance.CONCLUSION: The adjunctive use of L. reuteri and systemic antibiotics along with SRP showed similar improvement in all clinical periodontal parameters. This indicates that both adjunctive therapeutic agents showed similar efficacy in resolving inflammation and improving periodontal outcomes.

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PMID: 

Nutrients. 2019 Jan 21 ;11(1). Epub 2019 Jan 21. PMID: 30669695

Abstract Title: 

Lactobacillus reuteri DSM 17938 Protects against Gastric Damage Induced by Ethanol Administration in Mice: Role of TRPV1/Substance P Axis.

Abstract: 

This study aimed to evaluate the effect ofDSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 10⁸ CFU•g body wt•dayof DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940± 1.121 mm²) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 μmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels ofparameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.

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PMID: 

Am J Dent. 2019 Feb ;32(1):9-13. PMID: 30834725

Abstract Title: 

Clinical effect of Lactobacillus on the treatment of severe periodontitis and halitosis: A double-blinded, placebo-controlled, randomized clinical trial.

Abstract: 

PURPOSE: To evaluate the clinical association between Lactobacillus and the efficacy of adjuvant treatment of severe periodontitis, periodontal parameters, and halitosis.METHODS: 60 healthy volunteers with severe periodontitis were randomized into two groups to receive periodontal therapy in a single session and lactobacillus or a placebo for 90 days. The test group received Lactobacillus reuteri, salivarius and acidophilus, and the control group received placebo with xylitol.RESULTS: There was a reduction in the depth levels of the probing pocket and the level of relative attachment after 90 days (P

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PMID: 

Front Immunol. 2019 ;10:385. Epub 2019 Mar 7. PMID: 30899262

Abstract Title: 

Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Mice by Modulating Gut Microbiota.

Abstract: 

The gut microbiome plays an important role in immune function and has been implicated in multiple sclerosis (MS). However, how and if the modulation of microbiota can prevent or treat MS remain largely unknown. In this study, we showed that probioticDSM 17938 () ameliorated the development of murine experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, a model which is primarily mediated by T17 and T1 cells. We discovered thattreatment reduced T1/T17 cells and their associated cytokines IFN-γ/IL-17 in EAE mice. We also showed that the loss of diversity of gut microbiota induced by EAE was largely restored bytreatment. Taxonomy-based analysis of gut microbiota showed that three"beneficial"genera, andwere negatively correlated with EAE clinical severity, whereas the genera, andwere positively correlated with disease severity. Notably,treatment coordinately altered the relative abundance of these EAE-associated taxa. In conclusion, probioticchanged gut microbiota to modulate immune responses in EAE, making it a novel candidate in future studies to modify the severity of MS.

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PMID: 

Nutrients. 2019 Feb 28 ;11(3). Epub 2019 Feb 28. PMID: 30823406

Abstract Title: 

Pretreatment with a Heat-Killed Probiotic Modulates the NLRP3 Inflammasome and Attenuates Colitis-Associated Colorectal Cancer in Mice.

Abstract: 

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Inflammation contributes to cancer development and inflammatory bowel disease is an important risk factor for CRC. The aim of this study is to assess whether a widely used probioticcan modulate the NLRP3 inflammasome and protect against colitis and colitis-associated CRC. We studied the effect of heat-killed cells ofon NLRP3 inflammasome activation in THP-1-derived macrophages. Pretreatment ofor NLRP3 siRNA can inhibit NLRP3 inflammasome activation in macrophages in response to fecal content or commensal microbes,or, according to the reduction of caspase-1 activation and IL-1β maturation. Mechanistically,attenuates the phagocytosis that is required for the full activation of the NLRP3 inflammasome. In in vivo mouse experiments,can ameliorate the severity of intestinal inflammation and thereby protect mice from dextran sodium sulfate (DSS)-induced colitis and the formation of CRC in wild type mice. On the other hand,cannot prevent DSS-induced colitis in NLRP3 knockout mice. Our findings indicate that application of the inactivated probiotic,, may be a useful and safe strategy for attenuation of NLRP3-mediated colitis and inflammation-associated colon carcinogenesis.

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