PMID: 

Science. 2004 Sep 17 ;305(5691):1736-9. PMID: 15375259

Abstract Title: 

Inflammatory exposure and historical changes in human life-spans.

Abstract: 

Most explanations of the increase in life expectancy at older ages over history emphasize the importance of medical and public health factors of a particular historical period. We propose that the reduction in lifetime exposure to infectious diseases and other sources of inflammation–a cohort mechanism–has also made an important contribution to the historical decline in old-age mortality. Analysis of birth cohorts across the life-span since 1751 in Sweden reveals strong associations between early-age mortality and subsequent mortality in the same cohorts. We propose that a"cohort morbidity phenotype"represents inflammatory processes that persist from early age into adult life.

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PMID: 

Curr Opin Neurol. 2016 06 ;29(3):362-71. PMID: 27023738

Abstract Title: 

Vaccine-associated inflammatory diseases of the central nervous system: from signals to causation.

Abstract: 

PURPOSE OF REVIEW: As the most cost-effective intervention in preventive medicine and as a crucial element of any public health program, vaccination is used extensively with over 90% coverage in many countries. As approximately 5-8% of the population in developed countries suffer from an autoimmune disorder, people with an autoimmune disease are most likely to be exposed to some vaccines before or after the disease onset. In fact, a number of inflammatory disorders of the central nervous system have been associated with the administration of various vaccines. These adverse events, be they spurious associations or genuine reactions to the vaccine, may lead to difficulties in obtaining public trust in mass vaccination programs. There is, thus, an urgent need to understand whether vaccination triggers or enhances autoimmune responses.RECENT FINDINGS: By reviewing vaccine-associated inflammatory diseases of the central nervous system, this study describes the current knowledge on whether the safety signal was coincidental, as in the case of multiple sclerosis with several vaccines, or truly reflected a causal link, as in narcolepsy with cataplexy following pandemic H1N1 influenza virus vaccination.SUMMARY: The lessons learnt emphasize a central role of thorough, ideally prospective, epidemiological studies followed, if the signal is deemed plausible or real, by immunological investigations.

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PMID: 

Biol Trace Elem Res. 2007 Jun ;116(3):329-48. PMID: 17709913

Abstract Title: 

Involvement of oxidative stress in the impairment in biliary secretory function induced by intraperitoneal administration of aluminum to rats.

Abstract: 

We have shown that aluminum (Al) induces cholestasis associated with multiple alterations in hepatocellular transporters involved in bile secretory function, like Mrp2. This work aims to investigate whether these harmful effects are mediated by the oxidative stress caused by the metal. For this purpose, the capability of the antioxidant agent, vitamin E, to counteract these alterations was studied in male Wistar rats. Aluminum hydroxide (or saline in controls) was administered ip (27 mg/kg body weight, three times a week, for 90 d). Vitamin E (600 mg/kg body weight) was coadministered, sc. Al increased lipid peroxidation (+50%) and decreased hepatic glutation levels (-43%) and the activity of glutation peroxidase (-50%) and catalase (-88%). Vitamin E counteracted these effects total or partially. Both plasma and hepatic Al levels reached at the end of the treatment were significantly reduced by vitamin E (-40% and -44%, respectively; p

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PMID: 

Expert Rev Vaccines. 2014 Mar ;13(3):417-27. Epub 2014 Feb 6. PMID: 24502690

Abstract Title: 

The Yin-Yang arms of vaccines: disease-fighting power versus tissue-destructive inflammation.

Abstract: 

The disease-fighting power of vaccines has defeated many pathogens and has been credited with global reduction of mortality and morbidity. However, most vaccine developments focus on the enhancement of effector responses with systemic inflammation and the consequences overlooked. Recent evidence shows that systemic inflammatory phenotypes, acute or chronic, are both detrimental and should be avoided if possible. Since noninvasive vaccination by painless delivery of nasal vaccines and skin patch vaccines could elicit potent protective immunity without inducing systemic inflammation, it can be predicted that vaccinology will increasingly see the abandonment of the 'needle-injection' paradigm for vaccine development. The findings that specific viral particles could rapidly remodel the tissue environment postinfection in favor of some pathogens with the capacity to suppress others illustrate the pressing need for a deeper understanding of the underlying mechanisms in order to unlock the full potential of immunological intervention.

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PMID: 

Int J Biochem Cell Biol. 2005 Aug ;37(8):1727-37. Epub 2005 Apr 26. PMID: 15878691

Abstract Title: 

Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro.

Abstract: 

Recent epidemiological observations suggest that acetaminophen (paracetamol) may contribute to asthma morbidity. Impaired endogenous antioxidant defences may have a role in the pathogenesis of a number of inflammatory pulmonary diseases, including asthma. We studied the effect of acetaminophen on the intracellular level of reduced glutathione (GSH) with and without inhibitors of cytochrome P450 or prostaglandin H synthetase, and TNF-alpha, IL-6 and IL-8 protein production in human alveolar macrophages and type II pneumocytes in vitro. Following a 20 h incubation with acetaminophen, cytotoxicity was apparent from>or = 5 and>or = 10 mM in macrophages and type II pneumocytes, respectively. A time- and concentration-dependent decrease of intracellular GSH occurred after acetaminophen (0.05-1 mM) exposure (1-4 h) in pulmonary macrophages (up to 53%) and type II pneumocytes (up to 34%). Diethyldithiocarbamic acid, potassium ethyl xanthate, and indomethacin decreased significantly acetaminophen-induced GSH depletion in the two cell types tested, suggesting the involvement of cytochrome P450 (mainly CYP2E1) and/or prostaglandin H synthetase. In macrophages, acetaminophen decreased the secretion of TNF-alpha (at 4 and 24 h, concentration-related) and IL-6 (at 24 h, at 0.1 mM), and did not affect significantly IL-8 production. These in vitro observations demonstrate that clinically relevant concentrations of acetaminophen decreased: (i) intracellular GSH in human pulmonary macrophages and type II pneumocytes and (ii) the secretion of TNF-alpha and possibly IL-6 by human pulmonary macrophages. These findings provide experimental plausibility to the challenging observations that frequent use of APAP may be a risk factor for asthma morbidity.

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PMID: 

Neurotherapeutics. 2019 Dec 16. Epub 2019 Dec 16. PMID: 31845175

Abstract Title: 

Tanshinone IIA Ameliorates CNS Autoimmunity by Promoting the Differentiation of Regulatory T Cells.

Abstract: 

Tanshinone IIA (TSA), an important natural lipophilic diterpene compound from the traditional Chinese herb Salvia miltiorrhiza Bunge, has long been widely used for the prevention and treatment of various diseases because of its anti-inflammatory activities; however, the anti-inflammatory mechanism remains unknown. In the present work, we examined the effects of TSA on experimental autoimmune encephalomyelitis (EAE), a model of autoreactive T/B cell-mediated central nervous system (CNS) autoimmunity. The data showed that TSA significantly attenuates the severity of EAE when administered at the pre-onset and peak of clinical disease. In vivo, the protective effects of TSA on EAE mice are correlated with diminished inflammatory infiltration, demyelination, and GM-CSF-producing CD4T cells in the spinal cord and selectively increased regulatory T (Treg) cell frequencies in both the spinal cord and spleen. We further confirm that TSA can promote the polarization of naïve CD4T cells into Treg cells both by targeting dendritic cells (DCs) to drive transforming growth factorβ1 (TGF-β1) upregulation and by directly targeting naïve CD4T cells in vitro. Most importantly, we showed that TSA-induced Treg cells display an effective suppressive activity at a level comparable to TGF-β1-polarized Treg Cells in vitro and in vivo. Taken together, our data provide evidence that TSA can promote Treg cell differentiation, and TSA may have a promising application as a therapeutic agent for the treatment of neuroinflammatory diseases.

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PMID: 

Phytother Res. 2019 Dec 4. Epub 2019 Dec 4. PMID: 31802554

Abstract Title: 

The effect of nettle (Urtica dioica) supplementation on the glycemic control of patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Abstract: 

Type 2 diabetes mellitus (T2DM) is a major health problem, worldwide, that is associated with increased morbidity and mortality. Several randomized controlled clinical trials (RCTs) have investigated the effect of nettle (Urtica dioica) supplementation on markers of glycemic status in patients with T2DM, with conflicting results. Therefore, the present study assessed the effect of nettle on some glycemic parameters in patients with T2DM. A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science, from database inception up to June 2019, to identify RCTs investigating the effect of nettle supplementation on glycemic markers, including fasting blood sugar (FBS) concentrations, insulin levels, homeostasis model assessment-estimated insulin resistance index, and glycosylated hemoglobin percentage in adults with T2DM. The Cochrane Collaboration tool was used to assess the methodological quality of the included studies. Results of this meta-analysis were reported based on the random effects model. Eight RCTs, comprising 401 participants, were included in the present systematic review and meta-analysis. Based on the Cochrane Collaboration risk of bias tool, five studies were considered as good quality, one was fair, and two studies were poor, respectively. The results of the meta-analysis revealed a significant reduction in FBS concentrations (weighted mean difference [WMD]: -18.01 mg/dl, 95% confidence interval [CI]: -30.04 to -5.97, p

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PMID: 

Acta Sci Pol Technol Aliment. 2019 Jul-Sep;18(3):317-332. PMID: 31569913

Abstract Title: 

Effects of exercise and stevia on renal ischemia/reperfusion injury in rats.

Abstract: 

BACKGROUND: The present work was designed to study the effects of methanolic stevia extracts and aerobic exercise and combination of both on renal I/R injury in male rats.METHODS: 60 adult male Sprague-Dawley rats were subdivided into five equal groups as sham, control, exercise, stevia, and stevia plus exercise group. After 5 weeks of exercise and stevia, animals were exposed to 45 min of left renal ischemia and right nephrectomy followed by reperfusion. Serum creatinine, creatinine clearance, fractional Na excretion (FENa+), malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT) levels in kidney tissues were measured. Also, renal histopathology and the expression of caspase-3 by immunohistochemical examination were done.RESULTS: The results showed that stevia, exercise or combination of stevia and exercise caused a significant decrease in serum level of creatinine (p

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PMID: 

J Food Biochem. 2019 Nov 3:e13087. Epub 2019 Nov 3. PMID: 31680279

Abstract Title: 

Stevia residue extract alone and combination with allopurinol attenuate hyperuricemia in fructose-PO-induced hyperuricemic mice.

Abstract: 

The current project was designed to utilize flavonoids and chlorogenic acids enriched stevia residue extract (STVRE) against hyperuricemia (HU). The in vitro results showed that STVRE potently and synergistically inhibits Xanthine oxidase (XO) with allopurinol. The AFM results predicted that STVRE compounds bind with XO and alter its structure which further prevents the entrance of substrate with XO. These in vitro results were further confirmed in fructose-PO-induced hyperuricemic mice model. The results showed that supplementation of STVRE with allopurinol significantly attenuated HU, oxidative stress, and inflammation caused by UA via inhibiting the production of uric acid and lowering cyclooxygenase-2, tumor necrosis factor-alpha, prostaglandin E2, interleukin-6, and interleukin 1-beta levels in serum and renal tissues. Moreover, STVRE and allopurinol treatment attenuated, tubular dilation, infiltration of inflammatory cells, improved structure disorder of podocyte, and foot process fusion, and decreased glomerular basement membrane thickness. These findings suggested that STVRE can be used as an antihyperuricemic agent along with allopurinol. PRACTICAL APPLICATIONS: The results of present study showed that STVRE has a beneficial effect against fructose-PO-induced hyperuricemia by decreasing uric acid level, xanthine oxidase activity, improving oxidative stress and inflammation. These findings suggested that by-product of stevia (STVRE) enriched with polyphenolic compounds can be used as a functional ingredient against hyperuricemia and related diseases.

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PMID: 

Nutrients. 2019 Dec 12 ;11(12). Epub 2019 Dec 12. PMID: 31842388

Abstract Title: 

Effects of Stevia Extract on Postprandial Glucose Response, Satiety and Energy Intake: A Three-Arm Crossover Trial.

Abstract: 

: Non-nutritive sweeteners (NNS) are suggested to lower energy intake in the diet, but they have been paradoxically involved in the epidemic of obesity and Type 2 diabetes. Stevia is the least studied sweetener. This study aims to investigate the effect of stevia on postprandial glucose levels, appetite and food intake.METHODS: 30 participants (20 females/10 males; 26.1 (10.56) years; body mass index (BMI) 23.44 (3.42) Kg/m) took part in a three-arm crossover trial where they received preloads of water, sugar (60 g) and stevia (1 g) on three different days, followed by an ad libitum pizza lunch. Breakfast was standardised. A one-day diet diary was collected on each test day. Visual analogue scales (VAS) were used to assess subjective feelings of appetite. Blood glucose samples were collected at 30-min intervals until 120 min post lunch.RESULTS: Energy intake did not significantly differ between preloads for ad libitum meals (= 0.78) and overall day (= 0.33). VAS scores for hunger and desire to eat (DTE) were lower following stevia preload compared to water (

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