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PMID: 

Pharmacol Res. 2020 Feb ;152:104579. Epub 2019 Nov 30. PMID: 31790820

Abstract Title: 

Pharmacological, non-pharmacological and stem cell therapies for the management of autism spectrum disorders: A focus on human studies.

Abstract: 

In the last decade, the prevalence of autism spectrum disorders (ASD) has dramatically escalated worldwide. Currently available drugs mainly target some co-occurring symptoms of ASD, but are not effective on the core symptoms, namely impairments in communication and social interaction, and the presence of restricted and repetitive behaviors. On the other hand, transplantation of hematopoietic and mesenchymal stem cells in ASD children has been shown promising to stimulate the recruitment, proliferation, and differentiation of tissue-residing native stem cells, reducing inflammation, and improving some ASD symptoms. Moreover, several comorbidities have also been associated with ASD, such as immune dysregulation, gastrointestinal issues and gut microbiota dysbiosis. Non-pharmacological approaches, such as dietary supplementations with certain vitamins, omega-3 polyunsaturated fatty acids, probiotics, some phytochemicals (e.g., luteolin and sulforaphane), or overall diet interventions (e.g., gluten free and casein free diets) have been considered for the reduction of such comorbidities and the management of ASD. Here, interventional studies describing pharmacological and non-pharmacological treatments in ASD children and adolescents, along with stem cell-based therapies, are reviewed.

PMID: 

World J Stem Cells. 2019 Nov 26 ;11(11):990-1004. PMID: 31768225

Abstract Title: 

Ameliorating liver fibrosis in an animal model using the secretome released from miR-122-transfected adipose-derived stem cells.

Abstract: 

BACKGROUND: Recently, the exclusive use of mesenchymal stem cell (MSC)-secreted molecules, called secretome, rather than cells, has been evaluated for overcoming the limitations of cell-based therapy, while maintaining its advantages. However, the use of naïve secretome may not fully satisfy the specificity of each disease. Therefore, it appears to be more advantageous to use the functionally reinforced secretome through a series of processes involving physico-chemical adjustments or genetic manipulation rather than to the use naïve secretome.AIM: To determine the therapeutic potential of the secretome released from miR-122-transfected adipose-derived stromal cells (ASCs).METHODS: We collected secretory materials released from ASCs that had been transfected with antifibrotic miR-122 (MCM) and compared their antifibrotic effects with those of the naïve secretome (CM). MCM and CM were intravenously administered to the mouse model of thioacetamide-induced liver fibrosis, and their therapeutic potentials were compared.RESULTS: MCM infusion provided higher therapeutic potential in terms of: (A) Reducing collagen content in the liver; (B) Inhibiting proinflammatory cytokines; and (C) Reducing abnormally elevated liver enzymes than the infusion of the naïve secretome. The proteomic analysis of MCM also indicated that the contents of antifibrotic proteins were significantly elevated compared to those in the naïve secretome.CONCLUSION: We could, thus, conclude that the secretome released from miR-122-transfected ASCs has higher antifibrotic and anti-inflammatory properties than the naïve secretome. Because miR-122 transfection into ASCs provides a specific way of potentiating the antifibrotic properties of ASC secretome, it could be considered as an enhanced method for reinforcing secretome effectiveness.

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PMID: 

Front Pharmacol. 2019 ;10:1551. Epub 2020 Jan 21. PMID: 32038239

Abstract Title: 

Luteolin Exerts NeuroprotectionModulation of the p62/Keap1/Nrf2 Pathway in Intracerebral Hemorrhage.

Abstract: 

Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establishandmodels of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss. Also,, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch-like enoyl-coenzyme A hydratase (ECH)-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury, as indicatedtetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in bothandmodels of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

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PMID: 

Nan Fang Yi Ke Da Xue Xue Bao. 2011 Oct ;31(10):1641-8. PMID: 22027761

Abstract Title: 

1,3,4-tri-O-galloyl-6-O-caffeoyl-β-D-glucopyranose, a new anti-proliferative ellagitannin, regulates the expression of microRNAs in HepG(2) cancer cells.

Abstract: 

OBJECTIVE: MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation and apoptosis. 1, 3, 4-tri-O-galloyl-6-O-caffeoyl-β-D-glucopyranose (BJA32515) is a new natural ellagitannin compound extracted from Balanophora Japonica MAKINO. The effect of BJA32515 on the expression of miRNAs in cancer cells has not yet been explored. Objective The present study was carried out to examine the changes in miRNA expression profiles in human HepG(2) hepatocarcinoma cells following BJA32515 exposure.METHODS: The proliferation of BJA32515-exposed HepG(2) cells was assessed using a colorimetric assay (cell counting kit-8). The miRNA expression profile of the cancer cells was analyzed using a miRNA array and quantitative real-time PCR. Apoptosis was assessed by annexin V and propidium iodide staining.RESULTS: BJA32515 inhibited the cell proliferation and increased apoptosis in HepG(2) cancer cells. The exposure to BJA32515 also caused alterations in the miRNA expression profile in the cells, with 33 miRNAs upregulated and 59 down-regulated. The up-regulation of let-7a and miR-29a and the down-regulation of miR-373 and miR-197 were verified by quantitative real-time PCR. CONCLSION: BJA32515-modifed miRNA expression may mediate the antiproliferative effect of this compound in HepG(2) cancer cells.

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PMID: 

Pharm Res. 2010 Jun ;27(6):1027-41. Epub 2010 Mar 20. PMID: 20306121-regulation-of-micrornas-by-natural-agents-an-emerging-field-in-chemoprevention-and-chem

Abstract Title: 

Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research.

Abstract: 

In recent years, microRNAs have received greater attention in cancer research. These small, non-coding RNAs could inhibit target gene expression by binding to the 3' untranslated region of target mRNA, resulting in either mRNA degradation or inhibition of translation. miRNAs play important roles in many normal biological processes; however, studies have also shown that aberrant miRNA expression is correlated with the development and progression of cancers. The miRNAs could have oncogenic or tumor suppressor activities. Moreover, some miRNAs could regulate formation of cancer stem cells and epithelial-mesenchymal transition phenotype of cancer cells which are typically drug resistant. Furthermore, miRNAs could be used as biomarkers for diagnosis and prognosis, and thus miRNAs are becoming emerging targets for cancer therapy. Recent studies have shown that natural agents including curcumin, isoflavone, indole-3-carbinol, 3,3'-diindolylmethane, (-)-epigallocatechin-3-gallate, resveratrol, etc. could alter miRNA expression profiles, leading to the inhibition of cancer cell growth, induction of apoptosis, reversal of epithelial-mesenchymal transition, or enhancement of efficacy of conventional cancer therapeutics. These emerging results clearly suggest that specific targeting of miRNAs by natural agents could open newer avenues for complete eradication of tumors by killing the drug-resistant cells to improve survival outcome in patients diagnosed with malignancies.

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PMID: 

Microb Pathog. 2020 Feb 11 ;142:104056. Epub 2020 Feb 11. PMID: 32058023

Abstract Title: 

Antimicrobial mechanism of luteolin against Staphylococcus aureus and Listeria monocytogenes and its antibiofilm properties.

Abstract: 

Luteolin (LUT) is a naturally occurring compound found in a various of plants. Few recent studies have reported LUT antimicrobial activities against bacterial pathogens, however, the fundamental LUT mediated antimicrobial mechanism has never been elucidated. This study aimed to investigate the antimicrobial activities of LUT and its mode of action against Staphylococcus aureus and Listeria monocytogenes, either as planktonic cells or as biofilms. Here, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of LUT against S. aureus and L. monocytogenes were determined using the broth microdilution method, and the antimicrobial mode of LUT was elucidated by evaluating the variations in both cell membrane integrity and cell morphology. Moreover, the biofilm inhibition was measured by crystal violet staining assay, while its qualitative imaging was achieved by confocal laser scanning microscope and field emission scanning electron microscope. MIC and MBC values of LUT against S. aureus were 16-32 and 32-64 μg/mL, and 32-64 and 64-128 μg/mL for L. monocytogenes. LUT destroyed the cell membrane integrity, as evidenced by a significant increase in the number of non-viable cells, and well-defined variations in cell morphology. Moreover, LUT presented robust inhibitory effects on the biofilm formation,enhanced antibiotics diffusion within biofilms and killed efficiently mono- and dual-species biofilm cells. Overall, LUT demonstrates potent antimicrobial properties on planktonic and biofilm cells, and the biofilm formation, and thus has the potential use as a natural food preservative in foods.

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PMID: 

Oncol Res. 2019 Jul 12 ;27(7):773-778. Epub 2018 Mar 14. PMID: 29540256

Abstract Title: 

Luteolin Suppresses Teratoma Cell Growth and Induces Cell Apoptosis via Inhibiting Bcl-2.

Abstract: 

Luteolin, which is found in plant foods, has a range of therapeutic applications. In order to examine the potential roles of luteolin in ovarian teratocarcinoma, the human ovarian teratocarcinoma cell line PA-1 was selected for functional experiments in vitro and in vivo. We demonstrated that luteolin inhibited the proliferation and colony formation of PA-1 cells in vitro. The flow cytometry results suggested that luteolin induced apoptosis of PA-1 cells in a dose-dependent manner. Immunofluorescence and qRT-PCR results showed that the expression of B-cell lymphoma-2 (Bcl-2) was decreased in luteolin-treated cells, whereas the expression of Bcl-2-associated X (Bax) was increased compared with that in the control group. In addition, luteolin inhibited the tumor growth of ovarian teratocarcinoma cells in a xenograft model. All the results suggested that luteolin induced cell apoptosis and inhibited tumor growth of PA-1 cells.

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PMID: 

Benef Microbes. 2020 Feb 19 ;11(1):79-89. Epub 2020 Jan 14. PMID: 32066253

Abstract Title: 

probiotics improved the gut microbiota profile of aAlzheimer's disease model and alleviated neurodegeneration in the eye.

Abstract: 

Alzheimer's disease (AD) is a progressive disease and one of the most common forms of neurodegenerative disorders. Emerging evidence is supporting the use of various strategies that modulate gut microbiota to exert neurological and psychological changes. This includes the utilisation of probiotics as a natural and dietary intervention for brain health. Here, we showed the potential AD-reversal effects ofprobiotics through feeding to ourAD model. The administration ofstrains was able to rescue the rough eye phenotype (REP) seen in AD-induced, with a more prominent effect observed upon the administration ofDR7 (DR7). Furthermore, we analysed the gut microbiota of the AD-inducedand found elevated levels of. The administration of DR7 restored the gut microbiota diversity of AD-inducedwith a significant reduction in's relative abundance, accompanied by an increase ofand. Through functional predictive analyses,was predicted to be positively correlated with neurodegenerative disorders, such as Parkinson's, Huntington's and Alzheimer's diseases, whilewas negatively correlated with these neurodegenerative disorders. Altogether, our data exhibited DR7's ability to ameliorate the AD effects in our AD-induced. Thus, we propose thatbe used as a potential biomarker for AD.

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PMID: 

Prev Nutr Food Sci. 2019 Dec ;24(4):434-441. Epub 2019 Dec 31. PMID: 31915639

Abstract Title: 

Probiotic BSH Activity and Anti-Obesity Potential ofStrain TCI378 Isolated from Korean Kimchi.

Abstract: 

(.) is a human probiotic beneficial for the prevention and improvement of disease, yet properties of differentstrains are diverse. To obtain astrain that possesses greater potential against gastrointestinal dysfunction, we isolatedTCI378 (TCI378) from naturally fermented Korean kimchi. TCI378 has shown potential as probiotic since it can survive at pH 3.0 and in the presence of 0.3% bile acid. The bile salt hydrolase activity of TCI378 was shown by formation of opaque granular white colonies on solid de Man Rogosa Sharpe (MRS) medium supplemented with taurodeoxycholic acid, and its cholesterol-lowering ability in MRS medium supplemented with cholesterol. The metabolites of TCI378 from liquid culture in MRS medium prevented emulsification of bile salts. Moreover, both the metabolites of TCI378 and the dead bacteria reduced oil droplet accumulation in 3T3-L1, as detected by Oil red O staining. The expressions of adipocyte-specific genesandwere suppressed by the metabolites of TCI378, indicating TCI378 may have anti-obesity effects in adipocytes. Thesedata show the potential of the prophylactic applications of TCI378 and its metabolites for reducing fat and lowering cholesterol.

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PMID: 

Int J Mol Sci. 2020 Feb 12 ;21(4). Epub 2020 Feb 12. PMID: 32059401

Abstract Title: 

Probiotic Properties and Neuroprotective Effects ofKU200793 Isolated from Korean Fermented Foods.

Abstract: 

The purpose of this study was to evaluate the probiotic characteristics and neuroprotective effects of bacteria isolated from Korean fermented foods. Three bacterial strains (KU200060,KU200171, andKU200793) showed potential probiotic properties, such as high tolerance against artificial gastric juice and bile salts, sensitivity to antibiotics, nonproduction of carcinogenic enzymes, and high adhesion to intestinal cells. Heat-killedKU200060 andKU200793 showed higher antioxidant activity than heat-killedKU200171. The conditioned medium (CM) was used to evaluate the reaction between HT-29 cells and each heat-killed strain. All CMs protected SH-SY5Y cells from 1-methyl-4-phenylpyridinium (MPP)-induced toxicity. The expression of brain-derived neurotropic factor (BDNF) mRNA in HT-29 cells treated with CM containing heat-killedKU200793 was the highest. The CM significantly reduced the Bax/Bclratio and increased BDNF mRNA expression in SH-SY5Y cells treated with MPP. These results indicate thatKU200793 can be used as a prophylactic functional food, having probiotic potential and neuroprotective effects.

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