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PMID: 

Biol Trace Elem Res. 2013 Feb ;151(2):171-80. Epub 2012 Nov 29. PMID: 23192845

Abstract Title: 

Toxicological status of children with autism vs. neurotypical children and the association with autism severity.

Abstract: 

This study investigates both the level of toxic metals in children with autism and the possible association of those toxic metals with autism severity. This study involved 55 children with autism ages 5-16 years compared to 44 controls with similar age and gender. The study included measurements of toxic metals in whole blood, red blood cells (RBC), and urine. The autism group had higher levels of lead in RBC (+41 %, p = 0.002) and higher urinary levels of lead (+74 %, p = 0.02), thallium (+77 %, p = 0.0001), tin (+115 %, p = 0.01), and tungsten (+44 %, p = 0.00005). However, the autism group had slightly lower levels of cadmium in whole blood (-19 %, p = 0.003). A stepwise, multiple linear regression analysis found a strong association of levels of toxic metals with variation in the degree of severity of autism for all the severity scales (adjusted R(2) of 0.38-0.47, p<0.0003). Cadmium (whole blood) and mercury (whole blood and RBC) were the most consistently significant variables. Overall, children with autism have higher average levels of several toxic metals, and levels of several toxic metals are strongly associated with variations in the severity of autism for all three of the autism severity scales investigated.

PMID: 

J Toxicol. 2009 ;2009:532640. Epub 2009 Aug 26. PMID: 20107587

Abstract Title: 

The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels.

Abstract: 

This study investigated the relationship of children's autism symptoms with their toxic metal body burden and red blood cell (RBC) glutathione levels. In children ages 3-8 years, the severity of autism was assessed using four tools: ADOS, PDD-BI, ATEC, and SAS. Toxic metal body burden was assessed by measuring urinary excretion of toxic metals, both before and after oral dimercaptosuccinic acid (DMSA). Multiple positive correlations were found between the severity of autism and the urinary excretion of toxic metals. Variations in the severity of autism measurements could be explained, in part, by regression analyses of urinary excretion of toxic metals before and after DMSA and the level of RBC glutathione (adjusted R(2) of 0.22-0.45, P

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PMID: 

Molecules. 2019 Apr 5 ;24(7). Epub 2019 Apr 5. PMID: 30959759

Abstract Title: 

Antioxidant and Anti-Diabetic Activities of Polysaccharides from Guava Leaves.

Abstract: 

Guava (L., Myrtaceae) leaves have been used as a folk herbal tea to treat diabetes for a long time in Asia and North America. In this study, we isolated polysaccharides from guava leaves (GLP), and evaluated its antioxidant activity in vitro and anti-diabetic effects on diabetic mice induced by streptozotocin combined with high-fat diet. The results indicated that GLP exhibited good DPPH, OH, and ABTS free-radical scavenging abilities, and significantly lowered fasting blood sugar, total cholesterol, total triglycerides, glycated serum protein, creatinine, and malonaldehyde. Meanwhile, it significantly increased the total antioxidant activity and superoxide dismutase (SOD) enzyme activity in diabetic mice, as well as ameliorated the damage of liver, kidney, and pancreas. Thus, polysaccharides from guava leaves could be explored as a potential antioxidant or anti-diabetic agents for functional foods or complementary medicine.

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PMID: 

J Autoimmun. 2013 Dec ;47:1-16. Epub 2013 Nov 13. PMID: 24238833

Abstract Title: 

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects.

Abstract: 

In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance.

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PMID: 

Nutrients. 2019 Jul 3 ;11(7). Epub 2019 Jul 3. PMID: 31277259

Abstract Title: 

Guava () Fruit Extract Prepared by Supercritical COExtraction Inhibits Intestinal Glucose Resorption in a Double-Blind, Randomized Clinical Study.

Abstract: 

Inhibition of intestinal glucose resorption can serve as an effective strategy for the prevention of an increase in blood glucose levels. We have recently shown that various extracts prepared from guava () inhibit sodium-dependent glucose cotransporter 1 (SGLT1)- and glucose transporter 2 (GLUT2)-mediated glucose transport in vitro (Caco-2 cells) and in vivo (C57BL/6N mice). However, the efficacy in humans remains to be confirmed. For this purpose, we conducted a parallelized, randomized clinical study with young healthy adults. Thirty-one volunteers performed an oral glucose tolerance test (OGTT) in which the control group received a glucose solution and the intervention group received a glucose solution containing a guava fruit extract prepared by supercritical COextraction. The exact same extract was used for our previous in vitro and in vivo experiments. Blood samples were collected prior to and up to two hours after glucose consumption to quantitate blood glucose and insulin levels. Our results show that, in comparison to the control group, consumption of guava fruit extract resulted in a significantly reduced increase in postprandial glucose response over the basal fasting plasma glucose levels after 30 min (Δ control 2.60 ± 1.09 mmol/L versus Δ intervention 1.96 ± 0.96 mmol/L;= 0.039) and 90 min (Δ control 0.44 ± 0.74 mmol/L versus Δ intervention -0.18 ± 0.88 mmol/L;= 0.023). In addition, we observed a slightly reduced, but non-significant insulin secretion (Δ control 353.82 ± 183.31 pmol/L versus Δ intervention 288.43 ± 126.19 pmol/L,= 0.302). Interestingly, storage time and repeated freeze-thawing operations appeared to negatively influence the efficacy of the applied extract. Several analytical methods (HPLC-MS, GC-MS, and NMR) were applied to identify putative bioactive compounds in the COextract used. We could assign several substances at relevant concentrations including kojic acid (0.33 mg/mL) and 5-hydroxymethylfurfural (2.76 mg/mL). Taken together, this clinical trial and previous in vitro and in vivo experiments confirm the efficacy of our guava fruit extract in inhibiting intestinal glucose resorption, possibly in combination with reduced insulin secretion. Based on these findings, the development of food supplements or functional foods containing this extract appears promising for patients with diabetes and for the prevention of insulin resistance. Trial registration: 415-E/2319/15-2018 (Ethics Commissions of Salzburg).

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PMID: 

Food Funct. 2019 Jul 17 ;10(7):4189-4198. PMID: 31250851

Abstract Title: 

Identification of a new benzophenone from Psidium guajava L. leaves and its antineoplastic effects on human colon cancer cells.

Abstract: 

Psidium guajava L. leaves have a long history of being consumed as herbal teas in many countries. The aim of this study was to identify compounds with anticancer potentials from Psidium guajava L. leaves. Utilizing various extraction and chromatographical techniques, we have isolated one new (2) and two known compounds (1, 3). Structural analyses by the spectroscopic methods of TOF-MS, 1H NMR, 13C NMR, HSQC, and HMBC identified these three compounds as guavinoside E (1), 3,5-dihydroxy-2,4-dimethyl-1-O-(6'-O-galloyl-β-d-glucopyranosyl)-benzophenone (2), and guavinoside B (3). Cell viability assays showed that compounds 2 and 3 inhibited the growth of HCT116 human colon cancer cells in a dose-dependent manner, where compound 2 was more potent than compound 3. Based on flow cytometry analysis, compound 2 showedstronger activity in inducing cellular apoptosis in cancer cells than compound 3. Furthermore, compounds 2 and 3 modulated expression levels of key proteins involved in cell proliferation and apoptotic signaling. Specifically, compound 2 increased the levels of p53, p-ERK1/2, p-JNK, and cleaved caspases 8 and 9, and compound 3 increased the levels of p53 and cleaved caspase 8. Overall, this study provided identities of three bioactive compounds from P. guajava L. leaves and their anti-cancer effects against human colon cancer cells, which could facilitate the utilization of these compounds andP. guajava L. leaves as potential chemoprevention agents against colon carcinogenesis.

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PMID: 

Indian J Clin Biochem. 2019 Jul ;34(3):324-329. Epub 2018 Apr 11. PMID: 31391723

Abstract Title: 

Leaf Extracts and Their Quercetin Protect HepG2 Cell Lines Against CCLInduced Cytotoxicity.

Abstract: 

The present study was carried out to evaluate the in vitro cytoprotective effects ofand their isolated quercetin fraction to reduce the CCl(carbon tetrachloride) induced toxicity in HepG2 cell lines (Hepatocellular carcinoma G2). Silymarin was used as a standard drug to compare the protective effects of plant extracts in infected cell lines. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay, cell viability assay, leakage parameters [Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Lactate dehydrogenase (LDH)], lipid peroxidation and reduced glutathione (GSH) levels were used to find out the protection of human derived HepG2 cells against CCl-induced damage. The levels of cytotoxicity, viability and GSH were reduced. While the activities of AST, ALT, LDH and lipid peroxidation was increased in CCl-treated groups. The treatment ofand their isolated quercetin fractions (100, 200, 300 µg/mL) decreased the elevated levels of all these parameters. The results of the present study suggest that the ethanolic extract ofleaf and their isolated quercetin fractions can able to reduce the CCl-induced cytotoxicity in HepG2 cell lines.

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PMID: 

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Aug ;27(4):1094-1103. PMID: 31418363

Abstract Title: 

[Efficacy of Quercetin-sensitized Adriamycin for Treatment of Refractory Acute Leukemia].

Abstract: 

OBJECTIVE: To investigate the chemotherapeutic efficency of quercetin sensitized adriamycin.METHOD: CCK-8 was used to detect the inhibitory effect of different doses of adriamycin, quercetin and quercetin combined with adriamycin on the proliferation of primary leukemia cells from patients with clinically refractory acute leukemia. Quercetin, adriamycin and their combination were used to treat non-irradiated T-ALL leukemia mice to observe the changes of survival curve and myocardial injury.RESULT: There was no significant difference in the inhibition rate of primary leukemia cell proliferation between the adriamycin concentration group (6, 0.6 and 0.06μg/ml) and the adriamycin half-dose (3, 0.3 and 0.03 μg/ml) plus quercetin (0.25 mmol/L) group at three different time points (24, 48 and 72 hours). There was a significant difference in the inhibition rate of primary leukemia cell proliferation among the drug concentration groups, and the inhibition rate of primary leukemia cell proliferation was time-and concentration-dependent (r=0.995、r=1.000、r=0.984、r=0.993、r=0.999、r=0.960). In vivo experiments showed that the survival time of non-irradiated T-ALL leukemia mice treated with low-dose adriamycin combined with quercetin was not significantly prolonged compared with the high-dose adriamycin treatment group. The survival time of non-irradiated T-ALL leukemia mice treated with high dose of adriamycin and quercetin was significantly prolonged (P＜0.05). Compared with adriamycin group, the SOD activity in adriamycin combined with quercetin group increased significantly and the MDA content decreased. The results of transcriptome sequencing analysis showed that the expression of Ighv1-84 and Igkv6-14 in adriamycin combined quercetin group and quercetin group was lower than that in adriamycin group. The Ms4a1, Podx1, Mecom, Sh3bgr12, Bex4 and Tdrp expression in adriamycin combined quercetin group and adriamycin group were higher than that in quercetin group, while Crabp1 expression was lower.CONCLUSION: Quercetin can inhibit the proliferation of primary leukemia cells in a time-dependent manner. Quercetin combined with adriamycin inhibit the proliferation of primary leukemia cells significantly, and had synergistic and additive effects on the proliferation of primary leukemia cells, and the inhibiting effect of quercetin combined with adriamycin is concentration-and time-dependent. Quercetin combined with high-dose adriamycin can significantly prolong the survival time of non-irradiated T-ALL leukemia mice and reduce the myocardial damage caused by adriamycin.

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