PMID: 

J Med Food. 2019 Jul ;22(7):741-751. Epub 2019 May 22. PMID: 31120370

Abstract Title: 

, a Medicinal Plant for Appetite Suppression and Weight Loss.

Abstract: 

The prevalence of obesity is expanding rapidly worldwide, making the disease a global burden with limited treatment options. The current obesity drug development trends suggest the possibility of reducing weight and reverse metabolic disturbances of obesity by controlling appetite. In this study, we screened more than 8000 plants from our plant library for the cannabinoid (CB) receptor antagonists and identifiedas a lead medicinal plant. Kuwanon G and Albanin G were isolated and identified from root-barks ofwith 92% and 96% CBreceptor ligand binding inhibitory activity, respectively. The bioflavonoid standardized extract was tested in the acute food intake study in rats at oral doses of 250 and 500 mg/kg for its appetite suppression activity. Diet-induced obesity in the C57BL/6J mice was used to evaluate the long-term food intake reduction activity and effect on the weight loss administered orally at 250 and 500 mg/kg for 7 weeks. Statistically significant and dose-dependent reduction infood intake was observed in both acute and long-term studies for the extract. Food intake reductions of 58.6% and 44.8% at 250 mg/kg and 50.1% and 44.3% at 500 mg/kg were observed at 1 and 2 h postfood provision, respectively. A 20% reduction in daily calorie intake was observed in the long-term study. Obese mice treated with the high dose ofroot-bark extract showed 10.4 g (22.5%) and 7.1 g (16.5%) loss in body weight compared with the vehicle-treated obese animals (at week 7) and baseline, respectively. Statistically significant reductions in biochemical markers and visceral fat deposit were also observed. These results demonstrated thatextracts enriched in Kuwanon G, and Albanin G could be used alone to control appetite, manage body weight, and improve metabolic syndromes.

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PMID: 

Mol Biol Rep. 2020 Jan 25. Epub 2020 Jan 25. PMID: 31983015

Abstract Title: 

Inhibitory activity of black mulberry (Morus nigra) extract against testicular, liver and kidney toxicity induced by paracetamol in mice.

Abstract: 

Black mulberry (Morus nigra) leaves is broadly used in traditional medicine worldwide. However, there are no scientific reports regarding testicular protection, hepato-and nephroprotective activities of M. nigra leaves. The present investigation was assessed the protective mechanism by which methanol extract from M. nigra leaves suppressed the damaging effects induced by paracetamol (APAP) in different mouse tissues. Male mice were orally given APAP (500 mg/kg) with or without M. nigra extract (150, 300, and 500 mg/kg) for four consecutivedays. The results showed that crude extract possessed potent antioxidant activity (EC = 42.97 µg extract/mL) due to the presence of a high amount of polyphenol and flavonoid compounds. Gallic acid, chlorogenic acid, catechin, and rutin were isolated from the n-butanol fraction of M. nigra extract. Unexpectedly, oral administration of APAP did not induce chromosomal aberrationsin mouse bone marrow; however, it produced damaging effects on testis, liver, and kidney tissues. Interestingly, M. nigra extract suppressed APAP-induced genotoxicity by lowering meiotic chromosomal aberrations in spermatocytes, morphological sperm abnormalities, and % DNA damage in comet tail in the liver and kidney tissues. The altered levels of glutathione S transferase activity, lipid peroxidation, liver, and kidney functions were significantly reversed when M. nigra was given to APAP group. The restoring of the histo-architectural distortions and decreasing over-expression of p53 proteinas determined by immunohistochemistry in the liver, kidney, and testis sections were strengthened the protective activity of M. nigra extract. Conclusion, the bioactive components in the leaves of black mulberry appear to be a good candidate for genetic protection, treatment of oxidative stress-induced organotoxicity.

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PMID: 

Rev Peru Med Exp Salud Publica. 2019 Oct-Dec;36(4):573-582. Epub 2020 Jan 17. PMID: 31967248

Abstract Title: 

[Antimicrobial activity in vitro of Camu-Camu (Myrciaria Dubia) against oral microorganisms: a systematic review].

Abstract: 

OBJECTIVES.: To evaluate the antimicrobial activity of Myrciaria dubia on oral microorganisms.MATERIALS AND METHODS.: A systematic review of the literature following PRISMA guidelines was conducted through searches of studies published between 2008 and 2018 in Pubmed, LILACS, SciELO, ProQuest, EBSCO, and Google Scholar.RESULTS.: Eleven (11) in vitro studies were gathered; all the studies showed positive antimicrobial activity on gram-positives, mainly by each of the parts of its fruits. However, such activity compared to chlorhexidine in only two studies, and, in another study, it was better than an antibiotic. A high risk of bias was detected in most studies. Phenolic compounds, including polyphenols and acylphloroglucinols, were identified as responsible for its activity.CONCLUSIONS.: There is evidence of antimicrobial activity in M. dubia. Its study as an antimicrobial against oral microorganisms is still incipient, but there is great potential thanks to the potent phytochemicals it contains. Also, additional quality studies are required: comparing their activity versus oral antiseptics and on microorganisms associated with dental caries and periodontal disease.

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PMID: 

J Psychopharmacol. 2020 Feb ;34(2):155-166. Epub 2020 Jan 9. PMID: 31916890

Abstract Title: 

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer.

Abstract: 

BACKGROUND: A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60-80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses.METHODS: The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration.RESULTS: Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60-80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71-100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives.CONCLUSION: These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.

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PMID: 

Psychiatry Res. 2020 Jan 2 ;284:112749. Epub 2020 Jan 2. PMID: 31931272

Abstract Title: 

The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis.

Abstract: 

The current meta-analysis examined the effects of psilocybin in combination with behavioral interventions on anxiety and depression in samples with elevated symptoms. Across four studies (one uncontrolled; three randomized, placebo-controlled; N = 117), within-group pre-post and pre-follow-up effects on anxiety and depression were large (Hedges' gs=1.16 to 1.47) and statistically significant. Across three placebo-controlled studies, pre-post placebo-controlled effects were also large (gs = 0.82 to 0.83) and statistically significant. No serious adverse events were reported. Limitations include the small number of studies and risk for bias within studies. Results tentatively support future research on psilocybin for the treatment of anxiety and depression.

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PMID: 

J Psychopharmacol. 2020 Feb ;34(2):167-180. Epub 2020 Jan 16. PMID: 31941394

Abstract Title: 

Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression.

Abstract: 

BACKGROUND: Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed actions of antidepressants, we recently found increased amygdala responsiveness to fearful faces one day after open-label treatment with psilocybin (25 mg) in 19 patients with treatment-resistant depression, which correlated with treatment efficacy.AIMS: Aiming to further unravel the therapeutic mechanisms of psilocybin, the present study extends this basic activation analysis. We hypothesised changed amygdala functional connectivity, more precisely decreased amygdala-ventromedial prefrontal cortex functional connectivity, during face processing after treatment with psilocybin.METHODS: Psychophysiological interaction analyses were conducted on functional magnetic resonance imaging data from a classic face/emotion perception task, with the bilateral amygdala and ventromedial prefrontal cortex time-series as physiological regressors. Average parameter estimates (beta weights) of significant clusters were correlated with clinical outcomes at one week.RESULTS: Results showed decreased ventromedial prefrontal cortex-right amygdala functional connectivity during face processing post- (versus pre-) treatment; this decrease was associated with levels of rumination at one week. This effect was driven by connectivity changes in response to fearful and neutral (but not happy) faces. Independent whole-brain analyses also revealed a post-treatment increase in functional connectivity between the amygdala and ventromedial prefrontal cortex to occipital-parietal cortices during face processing.CONCLUSION: These results are consistent with the idea that psilocybin therapy revives emotional responsiveness on a neural and psychological level, which may be a key treatment mechanism for psychedelic therapy. Future larger placebo-controlled studies are needed to examine the replicability of the current findings.

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PMID: 

PLoS Pathog. 2019 10 ;15(10):e1008080. Epub 2019 Oct 28. PMID: 31658304

Abstract Title: 

Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies.

Abstract: 

Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10-3 subs/site/year and 8.9 x 10-4 subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.

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PMID: 

Proc Natl Acad Sci U S A. 2020 Jan 21. Epub 2020 Jan 21. PMID: 31964815

Abstract Title: 

Transformative experience and social connectedness mediate the mood-enhancing effects of psychedelic use in naturalistic settings.

Abstract: 

Past research suggests that use of psychedelic substances such as LSD or psilocybin may have positive effects on mood and feelings of social connectedness. These psychological effects are thought to be highly sensitive to context, but robust and direct evidence for them in a naturalistic setting is scarce. In a series of field studies involving over 1,200 participants across six multiday mass gatherings in the United States and the United Kingdom, we investigated the effects of psychedelic substance use on transformative experience, social connectedness, and positive mood. This approach allowed us to test preregistered hypotheses with high ecological validity and statistical precision. Controlling for a host of demographic variables and the use of other psychoactive substances, we found that psychedelic substance use was significantly associated with positive mood-an effect sequentially mediated by self-reported transformative experience and increased social connectedness. These effects were particularly pronounced for those who had taken psychedelic substances within the last 24 h (compared to the last week). Overall, this research provides robust evidence for positive affective and social consequences of psychedelic substance use in naturalistic settings.

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PMID: 

J Infect Dis. 2019 Jul 19 ;220(4):594-602. PMID: 30972418

Abstract Title: 

Early Measles Vaccination During an Outbreak in the Netherlands: Short-Term and Long-Term Decreases in Antibody Responses Among Children Vaccinated Before 12 Months of Age.

Abstract: 

BACKGROUND: The majority of infants will not be protected by maternal antibodies until their first measles vaccination, between 12 and 15 months of age. This provides incentive to reduce the age at measles vaccination, but immunological consequences are insufficiently understood, and long-term effects are largely unknown.METHODS: A total of 79 infants who received early measles vaccination between 6 and 12 months age and a second dose at 14 months of age were compared to 44 children in a control group who received 1 dose at 14 months of age. Measles virus-specific neutralizing antibody concentrations and avidity were determined up to 4 years of age.RESULTS: Infants who first received measles vaccination before 12 months of age had a long-term decrease in the concentration and avidity of measles virus-specific neutralizing antibodies, compared with infants in the control group. For 11.1% of children with a first dose before 9 months of age, antibody levels at 4 years of age had dropped below the cutoff for clinical protection.CONCLUSIONS: Early measles vaccination provides immediate protection in the majority of infants but yields a long-term decrease in neutralizing antibody responses, compared to vaccination at a later age. Additional vaccination at 14 months of age does not improve this. Over the long term, this may result in an increasing number of children susceptible to measles.

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PMID: 

Vaccine. 2018 10 1 ;36(41):6039-6042. Epub 2018 Sep 5. PMID: 30195487

Abstract Title: 

Non-live pentavalent vaccines after live measles vaccine may increase mortality.

Abstract: 

Live measles vaccine (MV) may have beneficial off-target/non-specific effects (NSEs) reducing child mortality beyond prevention of measles infection. In contrast, the non-live pentavalent (Diphtheria-Tetanus-Pertussis-H. influenzae Type B-Hepatitis B) vaccine has no beneficial NSEs. The NSEs are strongest for the most recent vaccine. Hence, sequence of vaccination may affect survival. In Guinea-Bissau, we followed 7094 measles-vaccinated children prospectively from first home visit after 9 months (when MV is scheduled) to 5 years of age. We compared survival by sequence of MV and third Pentavalent vaccine (Penta3; scheduled at 3½ months) in Cox proportional-hazards models. Compared with being vaccinated in-sequence (Penta3-then-MV), having received out-of-sequence Penta3-after-MV before the visit was associated with an adjusted Hazard Ratio (aHR) of 1.19 (95%CI: 0.84-1.69); Receiving missing Penta doses on the visit date tended to be associated with higher mortality (aHR = 1.87 (0.96-3.65)) while not receiving missing doses of Penta was not (aHR = 0.93 (0.57-1.54)), test for interaction p = 0.09.

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