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Article ; Online: Retraction Note: Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity.

Sidahmed, Heyam Mohamed Ali / Azizan, Ainnul Hamidah Syahadah / Mohan, Syam / Abdulla, Mahmood Ameen / Abdelwahab, Siddig Ibrahim / Taha, Manal Mohamed Elhassan / Hadi, A Hamid A / Ketuly, Kamal Aziz / Hashim, Najihah Mohd / Loke, Mun Fai / Vadivelu, Jamuna

BMC complementary medicine and therapies

2024 Volume 24, Issue 1, Page(s) 166

Language	English
Publishing date	2024-04-19
Publishing country	England
Document type	Retraction of Publication
ISSN	2662-7671
ISSN (online)	2662-7671
DOI	10.1186/s12906-024-04475-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Polymorphism of virulence genes and biofilm associated with in vitro induced resistance to clarithromycin in Helicobacter pylori.

Rosli, Naim Asyraf / Al-Maleki, Anis Rageh / Loke, Mun Fai / Chua, Eng Guan / Alhoot, Mohammed Abdelfatah / Vadivelu, Jamuna

Gut pathogens

2023 Volume 15, Issue 1, Page(s) 52

Abstract: Background: Clarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori ... ...

Abstract	Background: Clarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori strains that have evolved antibiotic resistance can help create a more effective and individualised antibiotic treatment plan. However, little is understood about the genetic reprogramming linked to clarithromycin exposure and the emergence of antibiotic resistance in H. pylori. Therefore, this study aims to identify compensatory mutations and biofilm formation associated with the development of clarithromycin resistance in H. pylori. Clarithromycin-sensitive H. pylori clinical isolates were induced to develop clarithromycin resistance through in vitro exposure to incrementally increasing concentration of the antibiotic. The genomes of the origin sensitive isolates (S), isogenic breakpoint (B), and resistant isolates (R) were sequenced. Single nucleotide variations (SNVs), and insertions or deletions (InDels) associated with the development of clarithromycin resistance were identified. Growth and biofilm production were also assessed. Results: The S isolates with A2143G mutation in the 23S rRNA gene were successfully induced to be resistant. According to the data, antibiotic exposure may alter the expression of certain genes, including those that code for the Cag4/Cag protein, the vacuolating cytotoxin domain-containing protein, the sel1 repeat family protein, and the rsmh gene, which may increase the risk of developing and enhances virulence in H. pylori. Enhanced biofilm formation was detected among R isolates compared to B and S isolates. Furthermore, high polymorphism was also detected among the genes associated with biofilm production. Conclusions: Therefore, this study suggests that H. pylori may acquire virulence factors while also developing antibiotic resistance due to clarithromycin exposure.
Language	English
Publishing date	2023-10-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2478277-4
ISSN	1757-4749
ISSN	1757-4749
DOI	10.1186/s13099-023-00579-4
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Article ; Online: Exposure of Helicobacter pylori to clarithromycin in vitro resulting in the development of resistance and triggers metabolic reprogramming associated with virulence and pathogenicity.

Rosli, Naim Asyraf / Al-Maleki, Anis Rageh / Loke, Mun Fai / Tay, Sun Tee / Rofiee, Mohd Salleh / Teh, Lay Kek / Salleh, Mohd Zaki / Vadivelu, Jamuna

PloS one

2024 Volume 19, Issue 3, Page(s) e0298434

Abstract: In H. pylori infection, antibiotic-resistance is one of the most common causes of treatment failure. Bacterial metabolic activities, such as energy production, bacterial growth, cell wall construction, and cell-cell communication, all play important ... ...

Abstract	In H. pylori infection, antibiotic-resistance is one of the most common causes of treatment failure. Bacterial metabolic activities, such as energy production, bacterial growth, cell wall construction, and cell-cell communication, all play important roles in antimicrobial resistance mechanisms. Identification of microbial metabolites may result in the discovery of novel antimicrobial therapeutic targets and treatments. The purpose of this work is to assess H. pylori metabolomic reprogramming in order to reveal the underlying mechanisms associated with the development of clarithromycin resistance. Previously, four H. pylori isolates were induced to become resistant to clarithromycin in vitro by incrementally increasing the concentrations of clarithromycin. Bacterial metabolites were extracted using the Bligh and Dyer technique and analyzed using metabolomic fingerprinting based on Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-Q-ToF-MS). The data was processed and analyzed using the MassHunter Qualitative Analysis and Mass Profiler Professional software. In parental sensitivity (S), breakpoint isolates (B), and induced resistance isolates (R) H. pylori isolates, 982 metabolites were found. Furthermore, based on accurate mass, isotope ratios, abundances, and spacing, 292 metabolites matched the metabolites in the Agilent METLIN precise Mass-Personal Metabolite Database and Library (AM-PCDL). Several metabolites associated with bacterial virulence, pathogenicity, survival, and proliferation (L-leucine, Pyridoxone [Vitamine B6], D-Mannitol, Sphingolipids, Indoleacrylic acid, Dulcitol, and D-Proline) were found to be elevated in generated resistant H. pylori isolates when compared to parental sensitive isolates. The elevated metabolites could be part of antibiotics resistance mechanisms. Understanding the fundamental metabolome changes in the course of progressing from clarithromycin-sensitive to breakpoint to resistant in H. pylori clinical isolates may be a promising strategy for discovering novel alternatives therapeutic targets.
MeSH term(s)	Helicobacter pylori ; Clarithromycin/pharmacology ; Virulence ; Metabolic Reprogramming ; Anti-Infective Agents
Chemical Substances	Clarithromycin (H1250JIK0A) ; Anti-Infective Agents
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0298434
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Article ; Online: SARS-CoV-2 Spike Protein and Mouse Coronavirus Inhibit Biofilm Formation by

Loke, Mun Fai / Yadav, Indresh / Lim, Teck Kwang / van der Maarel, Johan R C / Sham, Lok-To / Chow, Vincent T

International journal of molecular sciences

2022 Volume 23, Issue 6

Abstract: The presence of co-infections or superinfections with bacterial pathogens in COVID-19 patients is associated with poor outcomes, including increased morbidity and mortality. We hypothesized that SARS-CoV-2 and its components interact with the biofilms ... ...

Abstract	The presence of co-infections or superinfections with bacterial pathogens in COVID-19 patients is associated with poor outcomes, including increased morbidity and mortality. We hypothesized that SARS-CoV-2 and its components interact with the biofilms generated by commensal bacteria, which may contribute to co-infections. This study employed crystal violet staining and particle-tracking microrheology to characterize the formation of biofilms by
MeSH term(s)	Animals ; Antibiosis ; Biofilms ; Coinfection ; Coronavirus/physiology ; Gene Expression Regulation, Bacterial ; Humans ; Mice ; Microbial Interactions ; SARS-CoV-2/physiology ; Serogroup ; Spike Glycoprotein, Coronavirus/metabolism ; Staphylococcus aureus/classification ; Staphylococcus aureus/physiology ; Streptococcus pneumoniae/classification ; Streptococcus pneumoniae/physiology
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-03-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23063291
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Article ; Online: LC-MS analysis reveals biological and metabolic processes essential for Candida albicans biofilm growth.

Munusamy, Komathy / Loke, Mun Fai / Vadivelu, Jamuna / Tay, Sun Tee

Microbial pathogenesis

2020 Volume 152, Page(s) 104614

Abstract: Candidiasis is the most common fungal infection associated with high morbidity and mortality among immunocompromised patients. The ability to form biofilm is essential for Candida albicans pathogenesis and drug resistance. In this study, the planktonic ... ...

Abstract	Candidiasis is the most common fungal infection associated with high morbidity and mortality among immunocompromised patients. The ability to form biofilm is essential for Candida albicans pathogenesis and drug resistance. In this study, the planktonic cell and biofilm proteomes of C. albicans SC5314 strain analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS) were compared. In total, 280 and 449 proteins are annotated from the planktonic cell and biofilm proteomes, respectively. The biofilm proteome demonstrated significantly higher proportion of proteins associated with the endomembrane system, mitochondrion and cytoplasm than planktonic proteome. Among proteins detected, 143 and 207 biological processes are annotated, of which, 38 and 102 are specific to the planktonic cell and biofilm proteomes, respectively, while 105 are common biological processes. The specific biological processes of C. albicans planktonic cell proteome are associated with cell polarity, energy metabolism and nucleotide (purine) metabolism, oxido-reduction coenzyme metabolic process, monosaccharide and amino acid (methionine) biosynthesis, regulation of anatomical structure morphogenesis and cell cycling, and single organism reproduction. Meanwhile, regulation of cellular macromolecule biosynthesis and metabolism, transcription and gene expression are major biological processes specifically associated with C. albicans biofilm proteome. Biosynthesis of leucine, isoleucine, and thiocysteine are highlighted as planktonic-related pathways, whereas folate metabolism, fatty acid metabolism and biosynthesis of amino acids (lysine, serine and glycine) are highlighted as biofilm-related pathways. In summary, LC-MS-based proteomic analysis reveals different adaptative strategies of C. albicans via specific biological and metabolic processes for planktonic cell and biofilm lifestyles. The mass spectrometry data are available via ProteomeXchange with identifiers PXD007830 (for biofilm proteome) and PXD007831 (for planktonic cell proteome).
MeSH term(s)	Antifungal Agents ; Biofilms ; Biological Phenomena ; Candida albicans ; Chromatography, Liquid ; Humans ; Proteomics ; Tandem Mass Spectrometry
Chemical Substances	Antifungal Agents
Language	English
Publishing date	2020-11-14
Publishing country	England
Document type	Journal Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2020.104614
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Article ; Online: SARS-CoV-2 Spike Protein and Mouse Coronavirus Inhibit Biofilm Formation by Streptococcus pneumoniae and Staphylococcus aureus

Mun Fai Loke / Indresh Yadav / Teck Kwang Lim / Johan R. C. van der Maarel / Lok-To Sham / Vincent T. Chow

International Journal of Molecular Sciences, Vol 23, Iss 3291, p

2022 Volume 3291

Abstract	The presence of co-infections or superinfections with bacterial pathogens in COVID-19 patients is associated with poor outcomes, including increased morbidity and mortality. We hypothesized that SARS-CoV-2 and its components interact with the biofilms generated by commensal bacteria, which may contribute to co-infections. This study employed crystal violet staining and particle-tracking microrheology to characterize the formation of biofilms by Streptococcus pneumoniae and Staphylococcus aureus that commonly cause secondary bacterial pneumonia. Microrheology analyses suggested that these biofilms were inhomogeneous soft solids, consistent with their dynamic characteristics. Biofilm formation by both bacteria was significantly inhibited by co-incubation with recombinant SARS-CoV-2 spike S1 subunit and both S1 + S2 subunits, but not with S2 extracellular domain nor nucleocapsid protein. Addition of spike S1 and S2 antibodies to spike protein could partially restore bacterial biofilm production. Furthermore, biofilm formation in vitro was also compromised by live murine hepatitis virus, a related beta-coronavirus. Supporting data from LC-MS-based proteomics of spike–biofilm interactions revealed differential expression of proteins involved in quorum sensing and biofilm maturation, such as the AI-2E family transporter and LuxS, a key enzyme for AI-2 biosynthesis. Our findings suggest that these opportunistic pathogens may egress from biofilms to resume a more virulent planktonic lifestyle during coronavirus infections. The dispersion of pathogens from biofilms may culminate in potentially severe secondary infections with poor prognosis. Further detailed investigations are warranted to establish bacterial biofilms as risk factors for secondary pneumonia in COVID-19 patients.
Keywords	Streptococcus pneumoniae ; Staphylococcus aureus ; biofilm ; COVID-19 ; SARS-CoV-2 ; coronavirus ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Candida species and oral mycobiota of patients clinically diagnosed with oral thrush.

Karajacob, Alexandria Sonia / Azizan, Nuramirah Binti / Al-Maleki, Anis Rageh Mohammad / Goh, Joanne Pei En / Loke, Mun Fai / Khor, Hui Min / Ho, Gwo Fuang / Ponnampalavanar, Sasheela / Tay, Sun Tee

PloS one

2023 Volume 18, Issue 4, Page(s) e0284043

Abstract: Overgrowth of Candida yeasts in the oral cavity may result in the development of oral thrush in immunocompromised individuals. This study analyzed the diversity and richness of the oral mycobiota of patients clinically diagnosed with oral thrush (OT), ... ...

Abstract	Overgrowth of Candida yeasts in the oral cavity may result in the development of oral thrush in immunocompromised individuals. This study analyzed the diversity and richness of the oral mycobiota of patients clinically diagnosed with oral thrush (OT), follow-up of oral thrush patients after antifungal therapy (AT), and healthy controls (HC). Oral rinse and oral swab samples were collected from 38 OT patients, 21 AT patients, and 41 healthy individuals (HC). Pellet from the oral rinse and oral swab were used for the isolation of oral Candida yeasts on Brilliance Candida Agar followed by molecular speciation. ITS1 amplicon sequencing using Illumina MiSeq was performed on DNA extracted from the oral rinse pellet of 16 OT, 7 AT, and 7 HC oral rinse samples. Trimmed sequence data were taxonomically grouped and analyzed using the CLC Microbial Genomics Module workflow. Candida yeasts were isolated at significantly higher rates from oral rinse and swab samples of OT (68.4%, p < 0.001) and AT (61.9%, p = 0.012) patients, as compared to HC (26.8%). Predominance of Candida albicans specifically, was noted in OT (60.5%, p < 0.001) and AT (42.9%, p = 0.006) vs. HC (9.8%), while non-albicans Candida species was dominant in HC. Analysis of oral mycobiota from OT patients showed the presence of 8 phyla, 222 genera, and 309 fungal species. Low alpha diversity (Shannon index, p = 0.006; Chao-1 biased corrected index, p = 0.01), varied beta diversity (Bray-Curtis, p = 0.01986; Jaccard, p = 0.02766; Weighted UniFrac, p = 0.00528), and increased relative abundance of C. albicans (p = 3.18E-02) was significantly associated with the oral mycobiota of OT vs. HC. This study supported that C. albicans is the main etiological agent in oral thrush and highlights the association of fungal biodiversity with the pathophysiology of oral thrush.
MeSH term(s)	Humans ; Candidiasis, Oral/microbiology ; Candida ; Candida albicans ; Agar ; Antifungal Agents
Chemical Substances	Agar (9002-18-0) ; Antifungal Agents
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0284043
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Article ; Online: Authors' reply.

Koh, Sky Wei Chee / Li, Chun Fai / Loh, John Ser Pheng / Wong, Mun Loke / Loh, Victor Weng Keong

Singapore medical journal

2019 Volume 60, Issue 7, Page(s) 384

MeSH term(s)	Family Practice ; General Practice ; Humans ; Pain ; Pain Management
Language	English
Publishing date	2019-08-01
Publishing country	India
Document type	Letter ; Comment
ZDB-ID	604319-7
ISSN	2737-5935 ; 0037-5675
ISSN (online)	2737-5935
ISSN	0037-5675
DOI	10.11622/smedj.2019079
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Article ; Online: Candida species and oral mycobiota of patients clinically diagnosed with oral thrush.

Alexandria Sonia Karajacob / Nuramirah Binti Azizan / Anis Rageh Mohammad Al-Maleki / Joanne Pei En Goh / Mun Fai Loke / Hui Min Khor / Gwo Fuang Ho / Sasheela Ponnampalavanar / Sun Tee Tay

PLoS ONE, Vol 18, Iss 4, p e

2023 Volume 0284043

Abstract	Overgrowth of Candida yeasts in the oral cavity may result in the development of oral thrush in immunocompromised individuals. This study analyzed the diversity and richness of the oral mycobiota of patients clinically diagnosed with oral thrush (OT), follow-up of oral thrush patients after antifungal therapy (AT), and healthy controls (HC). Oral rinse and oral swab samples were collected from 38 OT patients, 21 AT patients, and 41 healthy individuals (HC). Pellet from the oral rinse and oral swab were used for the isolation of oral Candida yeasts on Brilliance Candida Agar followed by molecular speciation. ITS1 amplicon sequencing using Illumina MiSeq was performed on DNA extracted from the oral rinse pellet of 16 OT, 7 AT, and 7 HC oral rinse samples. Trimmed sequence data were taxonomically grouped and analyzed using the CLC Microbial Genomics Module workflow. Candida yeasts were isolated at significantly higher rates from oral rinse and swab samples of OT (68.4%, p < 0.001) and AT (61.9%, p = 0.012) patients, as compared to HC (26.8%). Predominance of Candida albicans specifically, was noted in OT (60.5%, p < 0.001) and AT (42.9%, p = 0.006) vs. HC (9.8%), while non-albicans Candida species was dominant in HC. Analysis of oral mycobiota from OT patients showed the presence of 8 phyla, 222 genera, and 309 fungal species. Low alpha diversity (Shannon index, p = 0.006; Chao-1 biased corrected index, p = 0.01), varied beta diversity (Bray-Curtis, p = 0.01986; Jaccard, p = 0.02766; Weighted UniFrac, p = 0.00528), and increased relative abundance of C. albicans (p = 3.18E-02) was significantly associated with the oral mycobiota of OT vs. HC. This study supported that C. albicans is the main etiological agent in oral thrush and highlights the association of fungal biodiversity with the pathophysiology of oral thrush.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Proteomics Analysis Revealed that Crosstalk between

Khosravi, Yalda / Loke, Mun Fai / Goh, Khean Lee / Vadivelu, Jamuna

Frontiers in microbiology

2016 Volume 7, Page(s) 1462

Abstract: Helicobacter ... ...

Abstract	Helicobacter pylori
Language	English
Publishing date	2016-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2016.01462
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