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1.
PLoS One ; 16(1): e0245038, 2021.
Article in English | MEDLINE | ID: mdl-33439913

ABSTRACT

BACKGROUND: Ischemic stroke is one of the non-communicable diseases that contribute to the significant number of deaths worldwide. However, the relationship between microbiome and ischemic stroke remained unknown. Hence, the objective of this study was to perform systematic review on the relationship between human microbiome and ischemic stroke. METHODS: A systematic review on ischemic stroke was carried out for all articles obtained from databases until 22nd October 2020. Main findings were extracted from all the eligible studies. RESULTS: Eighteen eligible studies were included in the systematic review. These studies suggested that aging, inflammation, and different microbial compositions could contribute to ischemic stroke. Phyla Firmicutes and Bacteroidetes also appeared to manipulate post-stroke outcome. The important role of microbiota-derived short-chain fatty acids and trimethylamine N-oxide in ischemic stroke were also highlighted. CONCLUSIONS: This is the first systematic review that investigates the relationship between microbiome and ischemic stroke. Aging and inflammation contribute to differential microbial compositions and predispose individuals to ischemic stroke.


Subject(s)
Fatty Acids, Volatile/metabolism , Ischemic Stroke/microbiology , Microbiota/physiology , Bacteroidetes/isolation & purification , Firmicutes/isolation & purification , Humans , Ischemic Stroke/metabolism
2.
J Zhejiang Univ Sci B ; 20(1): 59-70, 2019.
Article in English | MEDLINE | ID: mdl-30614230

ABSTRACT

Globally, peptide-based anticancer therapies have drawn much attention. Marine organisms are a reservoir of anticancer peptides that await discovery. In this study, we aimed to identify cytotoxic oligopeptides from Sarcophyton glaucum. Peptides were purified from among the S. glaucum hydrolysates produced by alcalase, chymotrypsin, papain, and trypsin, guided by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay on the human cervical cancer (HeLa) cell line for cytotoxicity evaluation. Purification techniques adopted were membrane ultrafiltration, gel filtration chromatography, solid phase extraction (SPE), and reversed-phase high-performance liquid chromatography (RP-HPLC). Purified peptides were identified by de novo peptide sequencing. From papain hydrolysate, three peptide sequences were identified: AGAPGG, AERQ, and RDTQ (428.45, 502.53, and 518.53 Da, respectively). Peptides synthesized from these sequences exhibited cytotoxicity on HeLa cells with median effect concentration (EC50) values of 8.6, 4.9, and 5.6 mmol/L, respectively, up to 5.8-fold stronger than the anticancer drug 5-fluorouracil. When tested at their respective EC50, AGAPGG, AERQ, and RDTQ showed only 16%, 25%, and 11% cytotoxicity to non-cancerous Hek293 cells, respectively. In conclusion, AERQ, AGAPGG, and RDTQ are promising candidates for future development as peptide-based anticancer drugs.


Subject(s)
Anthozoa/chemistry , Cytotoxins/isolation & purification , Marine Toxins/isolation & purification , Oligopeptides/isolation & purification , Amino Acid Sequence , Animals , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Chromatography, Gel , Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Cytotoxins/pharmacology , Drug Discovery , HEK293 Cells , HeLa Cells , Humans , Hydrolysis , Marine Toxins/pharmacology , Oligopeptides/pharmacology , Solid Phase Extraction , Tandem Mass Spectrometry
3.
Trop Life Sci Res ; 27(2): 73-90, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27688852

ABSTRACT

Probiotics are live microorganisms that can be found in fermented foods and cultured milk, and are widely used for the preparation of infant food. They are well-known as "health friendly bacteria", which exhibit various health beneficial properties such as prevention of bowel diseases, improving the immune system, for lactose intolerance and intestinal microbial balance, exhibiting antihypercholesterolemic and antihypertensive effects, alleviation of postmenopausal disorders, and reducing traveller's diarrhoea. Recent studies have also been focused on their uses in treating skin and oral diseases. In addition to that, modulation of the gut-brain by probiotics has been suggested as a novel therapeutic solution for anxiety and depression. Thus, this review discusses on the current probiotics-based products in Malaysia, criteria for selection of probiotics, and evidences obtained from past studies on how probiotics have been used in preventing intestinal disorders via improving the immune system, acting as an antihypercholesterolemic factor, improving oral and dermal health, and performing as anti-anxiety and anti-depressive agents.

4.
J Biochem ; 147(2): 201-11, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19819899

ABSTRACT

Oligopeptidase B from Trypanosoma brucei (Tb OPB) is a virulence factor and therapeutic target in African sleeping sickness. Three glutamic acid residues at positions 607, 609 and 610 of the catalytic domain are highly conserved in the OPB subfamily. In this study, the roles of Glu(607), Glu(609) and Glu(610) in Tb OPB were investigated by site-directed mutagenesis. A striking effect on k(cat)/K(m) was obtained following mutation of Glu(607) to glutamine. In contrast, the heat stability of Tb OPB decreased markedly following the single mutation of Glu(610) to glutamine, although this mutation had significantly less effect on catalytic properties compared with the Glu(607) mutation. Although no differences were found in the tertiary and secondary structures between wild-type (WT) OPB and the E610Q mutant prior to heat treatment, the E610Q mutant is inactivated more rapidly than WT OPB following heat treatment in a manner correlating with its attendant structural changes. Trypsin digestion showed that the boundary regions between the beta-propeller and catalytic domain of the E610Q mutant are unfolded with heat treatment. It is concluded that Glu(607) is essential for the catalytic activity of Tb OPB and that Glu(610) plays a critical role in stabilization rather than catalytic activity despite their close proximity.


Subject(s)
Glutamic Acid/physiology , Protozoan Proteins/metabolism , Serine Endopeptidases/metabolism , Trypanosoma brucei brucei/enzymology , Adrenocorticotropic Hormone/metabolism , Animals , Calorimetry, Differential Scanning , Circular Dichroism , Enzyme Activation/drug effects , Enzyme Stability/drug effects , Glucagon/metabolism , Glutamic Acid/chemistry , Glutamic Acid/genetics , Hot Temperature , Mutagenesis, Site-Directed , Mutation , Protozoan Proteins/chemistry , Protozoan Proteins/genetics , Salts/pharmacology , Serine Endopeptidases/chemistry , Serine Endopeptidases/genetics , Trypanosoma brucei brucei/genetics , Trypsin/metabolism , Urea/pharmacology
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