Publications by authors named "Tavan Janvilisri"

57 Publications

The repertoire of ABC proteins in .

Comput Struct Biotechnol J 2021 8;19:2905-2920. Epub 2021 May 8.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

ATP-binding cassette (ABC) transporters belong to one of the largest membrane protein superfamilies, which function in translocating substrates across biological membranes using energy from ATP hydrolysis. Currently, the classification of ABC transporters in is not complete. Therefore, the sequence-function relationship of all ABC proteins encoded within the genome was analyzed. Identification of protein domains associated with the ABC system in the 630 reference genome revealed 226 domains: 97 nucleotide-binding domains (NBDs), 98 transmembrane domains (TMDs), 30 substrate-binding domains (SBDs), and one domain with features of an adaptor protein. Gene organization and transcriptional unit analyses indicated the presence of 78 ABC systems comprising 28 importers and 50 exporters. Based on NBD sequence similarity, ABC transporters were classified into 12 sub-families according to their substrates. Interestingly, all ABC exporters, accounting for 64% of the total ABC systems, are involved in antibiotic resistance. Based on analysis of ABC proteins from 49 strains, the majority of core NBDs are predicted to be involved in multidrug resistance systems, consistent with the ability of this organism to survive exposure to an array of antibiotics. Our findings herein provide another step toward a better understanding of the function and evolutionary relationships of ABC proteins in this pathogen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.csbj.2021.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144104PMC
May 2021

SW178 sp. nov., an intestinal bacterium of feral chicken.

PeerJ 2021 27;9:e11050. Epub 2021 Apr 27.

Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, United States.

A Gram-positive, coccobacillus, white raised and circular with an entire edge colony, and obligately anaerobic bacterium, strain SW178 was isolated from the cecum content of feral chickens in Brookings, South Dakota, USA. The most closely related strain based on 16S rRNA gene sequence analysis of strain SW178 was ATCC 27756 ( ATCC 27756) with 96.94% similarity. The genome of strain SW178 is 3.18 Mbp with G+C content of 46.9 mol%. The optimal temperature and pH for growth in modified brain heart infusion (BHI-M) medium were 45 °C and pH 7.5, respectively. The sole carbon sources of the strain were dextrin, L-fucose, D-galacturonic, α-D-glucose, L-rhamnose and D-sorbitol. The primary cellular fatty acids were C, C and C dimethyl acetal (DMA). Based on the genotypic and phenotypic comparison, we proposed that strain SW178 belong to the genus in the family as a novel species, in which the name is proposed. The type strain is SW178 (= DSM 109242 = CCOS 1886).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.11050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086573PMC
April 2021

Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma.

Pharmaceuticals (Basel) 2021 Jan 11;14(1). Epub 2021 Jan 11.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ph14010051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826774PMC
January 2021

Reversal of cisplatin sensitization and abrogation of cisplatin-enriched cancer stem cells in 5-8F nasopharyngeal carcinoma cell line through a suppression of Wnt/β-catenin-signaling pathway.

Mol Cell Biochem 2021 Apr 9;476(4):1663-1672. Epub 2021 Jan 9.

Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand.

Nasopharyngeal carcinoma (NPC) is one of the rare cancers in western countries but predominant in Southeast Asian countries including Thailand. One major cause for failure of NPC chemotherapeutic treatments is reportedly correlated with the elevation of cancer stem cell (CSC) fractions. Thus, this present study aims to investigate the effect of cisplatin (CDDP) treatment on the enrichment of cancer stem-like cells (CSCs) and its associated signaling pathway in EBV-negative NPC cells. Cisplatin-pretreated 5-8F NPC cells (5-8F CDDP) were first generated by treating the cells with 0.5 μM cisplatin for 48 h. After the instant treatment, 5-8F CDDP showed increased IC values, demonstrating a decrease in CDDP sensitization. Besides, the proportion of NPC cells with cancer stem-like phenotypes comprising side population (SP), key stemness-related gene expressions including SOX2, ALDH1, CD24 was significantly enhanced. Additionally, 5-8F CDDP displayed the upregulation of β-catenin gene, suggesting its association with the CSC-initiating mechanism. Furthermore, a tankyrase inhibitor for Wnt/β-catenin pathway, XAV939, substantially reduced CSCs and retrieved the cisplatin sensitivity in 5-8F CDDP. This confirms that the Wnt/β-catenin signaling is accountable for rising of the CSC population in EBV-negative NPC. Finally, the combined treatment of CDDP and XAV939 exhibited lower 5-8F CDDP cell viability compared to the treatment of CDDP alone, suggesting the reversal of cisplatin sensitization. In conclusion, the enhancement of CSCs in 5-8F NPC cells caused by the instant cisplatin treatment is initially mediated through the upregulation of β-catenin and activation of Wnt/β-catenin signaling pathway. As a result, a primary chemotherapeutic treatment with closely monitoring the targeted Wnt/β-catenin signaling pathway could potentially prevent the development of CSCs and improve the treatment efficiency in NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-020-04045-6DOI Listing
April 2021

Rapid detection of Clostridium perfringens in food by loop-mediated isothermal amplification combined with a lateral flow biosensor.

PLoS One 2021 7;16(1):e0245144. Epub 2021 Jan 7.

Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand.

Clostridium perfringens is a key anaerobic pathogen causing food poisoning. Definitive detection by standard culture method is time-consuming and labor intensive. Current rapid commercial test kits are prohibitively expensive. It is thus necessary to develop rapid and cost-effective detection tool. Here, loop-mediated isothermal amplification (LAMP) in combination with a lateral-flow biosensor (LFB) was developed for visual inspection of C. perfringens-specific cpa gene. The specificity of the developed test was evaluated against 40 C. perfringens and 35 other bacterial strains, which showed no cross-reactivity, indicating 100% inclusivity and exclusivity. LAMP-LFB detection limit for artificially contaminated samples after enrichment for 16 h was 1-10 CFU/g sample, which was comparable to the commercial real-time PCR kit. The detection performance of LAMP-LFB was also compared to culture-based method using 95 food samples, which revealed the sensitivity (SE), specificity (SP) and Cohen's kappa coefficient (κ) of 88.0% (95% CI, 75.6%-95.4%), 95.5% (95% CI, 84.8%-99.4%) and 0.832 (95% CI, 0.721-0.943), respectively. Area under the receiver operating characteristic (ROC) curve was 0.918 (95% CI, 0.854-0.981), indicating LAMP-LFB as high relative accuracy test. In conclusion, LAMP-LFB assay is a low-cost qualitative method and easily available for routine detection of C. perfringens in food samples, which could serve as an alternative to commercial test kit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245144PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790239PMC
May 2021

Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells.

Cancer Res Treat 2021 Apr 7;53(2):457-470. Epub 2020 Oct 7.

Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.

Purpose: The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in patients with advanced CCA, the outcome of the standard-of-care chemotherapy treatment for CCA, gemcitabine/cisplatin, is discouraging so we determined the effect of other ErbB receptor inhibitors alone or in conjunction with chemotherapy in CCA cells.

Materials And Methods: ErbB receptor expression was determined in CCA patient tissues by immunohistochemistry and digital-droplet polymerase chain reaction, and in primary cells and cell lines by immunoblot. Effects on cell viability and cell cycle distribution of combination therapy using ErbB inhibitors with chemotherapeutic drugs was carried out in CCA cell lines. 3D culture of primary CCA cells was then adopted to evaluate the drug effect in a setting that more closely resembles in vivo cell environments.

Results: CCA tumors showed higher expression of all ErbB receptors compared with resection margins. Primary and CCA cell lines had variable expression of erbB receptors. CCA cell lines showed decreased cell viability when treated with chemotherapeutic drugs (gemcitabine and 5-fluorouracil) but also with ErbB inhibitors, particularly afatinib, and with a combination. Sequential treatment of gemcitabine with afatinib was particularly effective. Co-culture of CCA primary cells with cancer-associated fibroblasts decreased sensitivity to chemotherapies, but sensitized to afatinib.

Conclusion: Afatinib is a potential epidermal growth factor receptor targeted drug for CCA treatment and sequential treatment schedule of gemcitabine and afatinib could be explored in CCA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2020.585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053863PMC
April 2021

Taxono-genomics description of SW165 sp. nov., a new anaerobic bacterium isolated from cecum of feral chicken.

F1000Res 2020 8;9:1103. Epub 2020 Sep 8.

Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, 57007, USA.

The microbial community residing in the animal gastrointestinal tract play a crucial role in host health. Because of the high complexity of gut microbes, many microbes remain unclassified. Deciphering the role of each bacteria in health and diseases is only possible after its culture, identification, and characterization. During the culturomics study of feral chicken cecal sample, we cultured a possible novel strain SW165 . For the possible novel strain SW165 , phenotypic characterization was performed using colony morphology, Gram staining, growth in different temperature and pH and motility. Biochemical assays included carbon source utilization, enzymatic activity, cellular fatty acids and short chain fatty acid production. 16S rRNA sequencing and whole genome sequencing and comparison was performed for genetic analysis. This strain was isolated from cecal content of feral chickens in Brookings, South Dakota, USA. Phylogenetic analyses based on 16S rRNA gene sequence revealed that the closest valid neighbor was DSM 13989 (96.33% similarity) within the family . Cells were Gram-strain-positive and obligately anaerobic bacilli in chains. The optimum temperature and pH for the growth of the microorganism were 37-45 C and pH 6.0-7.5 respectively.  This strain produced acetic acid as the primary fermentation product. Major fatty acids were C , C , C DMA and summed feature 1 (C at 12-13 and C aldehyde). Strain SW165 exhibited a genome size of 2.43 Mbp with a G+C content of 67.59 mol%, which is the second highest G+C content among members of the genus . The digital DNA-DNA hybridization and OrthoANI values between SW165 and DSM 13989 were only 17.6 ± 5.3 and 74.35%, respectively. Based on the phenotypic, biochemical, and genomic analyses, we propose the new species of the genus and name it SW165 sp. nov., (=DSM 107283 =CCOS 1887) as the type strain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/f1000research.25823.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520715PMC
April 2021

Lectin affinity chromatography and quantitative proteomic analysis reveal that galectin-3 is associated with metastasis in nasopharyngeal carcinoma.

Sci Rep 2020 10 5;10(1):16462. Epub 2020 Oct 5.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Nasopharyngeal carcinoma (NPC) is a serious cancer in East and Southeast Asia. Patients are often diagnosed at advanced stages, rendering treatment failure due to high potential of metastasis. This study identified lectin-binding glycoproteins with a potential role in NPC metastasis. Cell lysate and culture medium in highly metastatic 5-8F, and lowly-metastatic 6-10B NPC cell lines were fractionated by ConA- and WGA-affinity chromatography, and subjected to GeLC-MS/MS. A total of 232 and 197 proteins were identified in ConA-enriched fraction of 5-8F and 6-10B cell lysates respectively. In WGA-enriched fraction, 65 and 164 proteins were found in 5-8F and 6-10B cell lysates respectively. Proteins identified in culture medium for both cell lines were 223 and 85 for ConA-enriched fraction, and 94 and 124 for WGA-enriched fraction from 5-8F and 6-10B respectively. Differentially expressed proteins were functionally categorized into cell-cell adhesion, extracellular matrix, glycolysis, protein homeostasis and/or glycosylation enzymes, and lipid metabolism. Interestingly, Galectin-3 (Gal-3) was highly expressed in 5-8F cells but was lowly expressed in 6-10B cells. The Gal-3 knockdown in 5-8F cells, Gal-3 overexpression in 6-10B cells and treatment with Gal-3 inhibitor revealed that Gal-3 was responsible for metastatic phenotypes including adhesion, migration and invasion. So Galectin-3 may serve as a potential target for NPC therapeutic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-73498-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536187PMC
October 2020

Epstein-Barr Virus Mediated Signaling in Nasopharyngeal Carcinoma Carcinogenesis.

Cancers (Basel) 2020 Aug 28;12(9). Epub 2020 Aug 28.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Nasopharyngeal carcinoma (NPC) is one of the most common tumors occurring in China and Southeast Asia. Etiology of NPC seems to be complex and involves many determinants, one of which is Epstein-Barr virus (EBV) infection. Although evidence demonstrates that EBV infection plays a key role in NPC carcinogenesis, the exact relationship between EBV and dysregulation of signaling pathways in NPC needs to be clarified. This review focuses on the interplay between EBV and NPC cells and the corresponding signaling pathways, which are modulated by EBV oncoproteins and non-coding RNAs. These altered signaling pathways could be critical for the initiation and progression of NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12092441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565514PMC
August 2020

Dysregulation of microRNA in cholangiocarcinoma identified through a meta-analysis of microRNA profiling.

World J Gastroenterol 2020 Aug;26(29):4356-4371

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Background: In the past decades, the potential of microRNA (miRNA) in cancer diagnostics and prognostics has gained a lot of interests. In this study, a meta-analysis was conducted upon the pooled miRNA microarray data of cholangiocarcinoma (CCA).

Aim: To identify differentially expressed (DE) miRNAs and perform functional analyses in order to gain insights to understanding miRNA-target interactions involved in tumorigenesis pathways of CCA.

Methods: Raw data from 8 CCA miRNA microarray datasets, consisting of 443 samples in total, were integrated and statistically analyzed to identify DE miRNAs comparison of levels of miRNA expression between CCA and normal bile duct samples using -tests ( < 0.001). The 10-fold cross validation was performed in order to increase the robustness of the -test results.

Results: Our data showed 70 up-regulated and 48 down-regulated miRNAs in CCA. Gene Ontology and pathway enrichment analyses revealed that mRNA targets of DE miRNAs were significantly involved in several biological processes. The most prominent dysregulated pathways included phosphatidylinositol-3 kinases/Akt, mitogen-activated protein kinase and Ras signaling pathways.

Conclusion: DE miRNAs found in our meta-analysis revealed dysregulation in major cancer pathways involved in the development of CCA. These results indicated the necessity of understanding the miRNA-target interactions and the significance of dysregulated miRNAs in terms of diagnostics and prognostics of cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v26.i29.4356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422534PMC
August 2020

In vitro analysis of the anticancer activity of binary toxin in human cancer cell lines.

3 Biotech 2020 Aug 31;10(8):365. Epub 2020 Jul 31.

Institute of Molecular Biosciences, Mahidol University, Salaya, Phuttamonthon, Nakhon Pathom, 73170 Thailand.

Binary or Bin toxin produced by is composed of BinA (42 kDa) and BinB (51 kDa) subunits. These work together to exert maximal toxicity against mosquito larvae via pore formation and induction of apoptosis. The C-terminal domains in both subunits are homologous to those of aerolysin-type β pore-forming toxins, including parasporin-2 (PS2). The latter is one of the toxins that exhibits specific cytotoxicity against human cancer cells. The present study investigates the possible anticancer activity of Bin toxin using PS2 as a control. We demonstrate that treatment with a high concentration of trypsin-activated Bin inhibits cell proliferation in human cancer cells A549, Caco-2, HepG2, HK-1 and KKU-M055. In the most susceptible cells, HK-1, Bin toxin exposure led to morphological alterations, decreased migration, decreased adhesion activity and apoptosis induction. Although these effects necessitated high concentrations, they suggest that Bin toxin may be optimized as a novel potential cancer-therapeutic agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13205-020-02361-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394974PMC
August 2020

Isolation and characterization of thermophilic cellulose and hemicellulose degrading bacterium, Thermoanaerobacterium sp. R63 from tropical dry deciduous forest soil.

PLoS One 2020 23;15(7):e0236518. Epub 2020 Jul 23.

Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand.

Thermophilic microorganisms and their enzymes have been utilized in various industrial applications. In this work, we isolated and characterized thermophilic anaerobic bacteria with the cellulose and hemicellulose degrading activities from a tropical dry deciduous forest in northern Thailand. Out of 502 isolated thermophilic anaerobic soil bacteria, 6 isolates, identified as Thermoanaerobacterium sp., displayed an ability to utilize a wide range of oligosaccharides and lignocellulosic substrates. The isolates exhibited significant cellulase and xylanase activities at high temperature (65°C). Among all isolates, Thermoanaerobacterium sp. strain R63 exhibited remarkable hydrolytic properties with the highest cellulase and xylanase activities at 1.15 U/mg and 6.17 U/mg, respectively. Extracellular extract of Thermoanaerobacterium sp. strain R63 was thermostable with an optimal temperature at 65°C and could exhibit enzymatic activities on pH range 5.0-9.0. Our findings suggest promising applications of these thermoanaerobic bacteria and their potent enzymes for industrial purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236518PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377481PMC
September 2020

CRISPR/Cas9-mediated double knockout of SRPK1 and SRPK2 in a nasopharyngeal carcinoma cell line.

Cancer Rep (Hoboken) 2020 04 27;3(2):e1224. Epub 2019 Nov 27.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

Background: Serine-arginine protein kinase (SRPK) is a regulator of alternative splicing events via phosphorylation of splicing factor proteins. Oncogenic roles of SRPK1 and SRPK2 have been reported in various types of cancer. To date, only SRPK1/2 specific inhibitors and small interfering RNA (siRNA) have been used for halting their function momentarily; however, there is no attempt to generate SRPK1/2 stable knockout cancer cells as a tool to investigate their roles in tumorigenesis.

Aim: Our objective is therefore to establish a nasopharyngeal carcinoma (NPC) cell line with stable SRPK1 or SRPK2 knockout and SRPK1/2 double knockout as a model to investigate their potential roles in NPC.

Methods And Results: CNE1 was selected as a representative of NPC cell lines to create single and double knockout of SRPK1/2 proteins. SRPK1/2 KO plasmid with cas9, green fluorescent protein (GFP), and gRNA expression was cotransfected with SRPK1/2 homology-directed repair (HDR) plasmid containing puromycin resistance, red fluorescent protein (RFP), and 5' and 3' arm sequence for homologous recombination to CNE1 cells. The transfected CNE1 cells with GFP and RFP expression were sorted through fluorescence-activated cell sorting for further treatment with puromycin containing medium. This step generated stable single knockout of SRPK1 and SRPK2. The SRPK2 knockout NPC cells were used as a precursor for double knockout generation via transfection with Cre plasmid for excision of inserted material to generate puromycin-sensitive SRPK2 knockout clone. The puromycin-sensitive SRPK2 knockout cells were transfected with SRPK1 KO/HDR plasmid and treated with puromycin-containing medium. The puromycin-resistant cells of SRPK1/2 stable double knockout were expanded, and the corresponding protein expression was confirmed by western immunoblotting analysis.

Conclusion: Single and double knockout of SRPK1/2 were established using clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated 9 (Cas9) system in an NPC cell line as a model for investigation of their splicing mechanism in NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cnr2.1224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941449PMC
April 2020

Repurposing a platelet aggregation inhibitor ticagrelor as an antimicrobial against Clostridioides difficile.

Sci Rep 2020 04 16;10(1):6497. Epub 2020 Apr 16.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Drug resistance in Clostridioides difficile becomes a public health concern worldwide, especially as the hypervirulent strains show decreased susceptibility to the first-line antibiotics for C. difficile treatment. Therefore, the simultaneous discovery and development of new compounds to fight this pathogen are urgently needed. In order to determinate new drugs active against C. difficile, we identified ticagrelor, utilized for the prevention of thrombotic events, as exhibiting potent growth-inhibitory activity against C. difficile. Whole-cell growth inhibition assays were performed and compared to vancomycin and metronidazole, followed by determining time-kill kinetics against C. difficile. Activities against biofilm formation and spore germination were also evaluated. Leakage analyses and electron microscopy were applied to confirm the disruption of membrane structure. Finally, ticagrelor's ability to synergize with vancomycin and metronidazole was determined using checkerboard assays. Our data showed that ticagrelor exerted activity with a MIC range of 20-40 µg/mL against C. difficile. This compound also exhibited an inhibitory effect on biofilm formation and spore germination. Additionally, ticagrelor did not interact with vancomycin nor metronidazole. Our findings revealed for the first time that ticagrelor could be further developed as a new antimicrobial agent for fighting against C. difficile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-63199-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162883PMC
April 2020

Lapatinib sensitivity in nasopharyngeal carcinoma is modulated by SIRT2-mediated FOXO3 deacetylation.

BMC Cancer 2019 Nov 14;19(1):1106. Epub 2019 Nov 14.

Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, W12 0NN, UK.

Background: Chemoresistance is an obstacle to the successful treatment of nasopharyngeal carcinoma (NPC). Lapatinib is a targeted tyrosine kinase inhibitor therapeutic drug also used to treat NPC, but high doses are often required to achieve a result. To investigate the mechanism for the development of Lapatinib resistance, we characterised a number of NPC cell lines to determine the role of FOXO3 and sirtuins in regulating NPC resistance.

Methods: Sulforhodamine B (SRB) assays, Clonogenic assays, Protein extraction, quantification and western blotting, RT qPCR, Co-immunoprecipitation assay.

Results: To explore novel treatment strategies, we first characterized the Lapatinib-sensitivity of a panel of NPC cell lines by SRB and clonogenic cytotoxic assays and found that the metastatic NPC (C666-1 and 5-8F) cells are highly resistant whereas the poorly metastatic lines (6-10B, TW01 and HK-1) are sensitive to Lapatinib. Western blot analysis of the Lapatinib-sensitive 6-10B and resistant 5-8F NPC cells showed that the expression of phosphorylated/inactive FOXO3 (P-FOXO3;T32), its target FOXM1 and its regulator SIRT2 correlate negatively with Lapatinib response and sensitivity, suggesting that SIRT2 mediates FOXO3 deacetylation to promote Lapatinib resistance. In agreement, clonogenic cytotoxic assays using wild-type and foxo1/3/4 mouse embryonic fibroblasts (MEFs) showed that FOXO1/3/4-deletion significantly attenuates Lapatinib-induced cytotoxicity, confirming that FOXO proteins are essential for mediating Lapatinib response. SRB cell viability assays using chemical SIRT inhibitors (i.e. sirtinol, Ex527, AGK2 and AK1) revealed that all SIRT inhibitors can reduce NPC cell viability, but only the SIRT2-specific inhibitors AK1 and AGK2 further enhance the Lapatinib cytotoxicity. Consistently, clonogenic assays demonstrated that the SIRT2 inhibitors AK1 and AGK2 as well as SIRT2-knockdown increase Lapatinib cytotoxicity further in both the sensitive and resistant NPC cells. Co-immunoprecipitation studies showed that besides Lapatinib treatment, SIRT2-pharmaceutical inhibition and silencing also led to an increase in FOXO3 acetylation. Importantly, SIRT2 inhibition and depletion further enhanced Lapatinib-mediated FOXO3-acetylation in NPC cells.

Conclusion: Collectively, our results suggest the involvement of SIRT2-mediated FOXO3 deacetylation in Lapatinib response and sensitivity, and that SIRT2 can specifically antagonise the cytotoxicity of Lapatinib through mediating FOXO3 deacetylation in both sensitive and resistant NPC cells. The present findings also propose that SIRT2 can be an important biomarker for metastatic and Lapatinib resistant NPC and that targeting the SIRT2-FOXO3 axis may provide novel strategies for treating NPC and for overcoming chemoresistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-019-6308-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854897PMC
November 2019

Downregulation of ABCA1 and ABCG1 transporters by simvastatin in cholangiocarcinoma cells.

Oncol Lett 2019 Nov 17;18(5):5173-5184. Epub 2019 Sep 17.

Department of Biology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Disturbances in cholesterol homeostasis of the bile duct epithelium, including transport interruption and the hyperaccumulation of intracellular cholesterol can lead to the initiation and progression of cholangiocarcinoma (CCA). Statins, which are lipid-lowering drugs, have been previously documented to exhibit anti-cancer properties. The role of statins in CCA cell cholesterol transport through the expression and function of ATP-binding cassette (ABC) A1 and ABCG1 was investigated in the current study. In four CCA cell lines, ABCA1 and ABCG1 expression was identified. However, neither ABCG5 nor ABCG8 expression was observed. Immunocytochemistry revealed that the expression of ABCA1 was localized in the proximity of the nucleus, while ABCG1 was more dispersed throughout the cytoplasm of KKU-100 cells. A cholesterol efflux assay was performed using bodipy cholesterol, and the translocation of cholesterol via ABCA1 and ABCG1 to Apo-A1 and high density lipoprotein was confirmed, respectively. Simvastatin and atorvastatin demonstrated the inhibitory effects on CCA cell viability. A reduction in intracellular lipid level and a lower expression of ABCA1 and ABCG1 were observed in KKU-100 cells under simvastatin treatment. The pre-exposure of KKU-100 cells to cholesterol diminished the statin effect. Furthermore, when KKU-100 cells were pre-loaded with cholesterol, ABCA1 and ABCG1-mediated exports were unaffected even though they were treated with simvastatin. The results of the current study indicated the limitations of the use of statin in CCA therapy, particularly under hypercholesterolemia conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2019.10874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781495PMC
November 2019

Andrographolide Inhibits Cholangiocarcinoma Cell Migration by Down-Regulation of Claudin-1 the p-38 Signaling Pathway.

Front Pharmacol 2019 25;10:827. Epub 2019 Jul 25.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

Andrographolide, a bioactive phytochemical from , is emerging as a promising anticancer agent against various cancers. This study aims to investigate anticancer activities of andrographolide against cholangiocarcinoma (CCA) and to understand the underlying mechanism. The anti-proliferative activity of andrographolide was evaluated in a range of cholangiocarcinoma (CCA) cell lines including HuCCA-1, KKU-100, KKU-M213, and RMCCA-1. The anti-migration activity and the corresponding mechanism were studied in highly metastatic KKU-M213 cells. The results indicated that andrographolide significantly inhibited the proliferation of CCA cells with the 50% inhibitory growth concentration (IC) of ∼120 µM. Andrographolide also inhibited CCA cell migration and invasion. Our further explorations demonstrated that andrographolide decreased the expression of claudin-1, a major tight junction protein, while it up-regulated the expression of Snail, a transcriptional repressor of claudin-1. Moreover, andrographolide induced the phosphorylation of Jun N-terminus kinase (JNK) and p-38 Mitogen-activated protein kinase (MAPK). Treatment with the p-38-specific inhibitor recovered the claudin-1 expression and migration ability of CCA cells. This work demonstrated the potential anticancer effects of andrographolide, indicating that andrographolide could inhibit CCA cell migration suppression of claudin-1 through the activation of p-38 MAPK signaling pathway. This compound would be useful for development of alternative therapeutic agent for CCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2019.00827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669233PMC
July 2019

Editorial: Alternative Therapeutic Approaches For Multidrug Resistant .

Front Microbiol 2019 31;10:1216. Epub 2019 May 31.

Biotechnology Institute, University of Minnesota, Saint Paul, MN, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2019.01216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554321PMC
May 2019

Gut Microbial Dynamics during Conventionalization of Germfree Chicken.

mSphere 2019 03 27;4(2). Epub 2019 Mar 27.

Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA

A gnotobiotic (chicken) model was developed to study the dynamics of intestinal microflora from hatching to 18 days of age employing metagenomics. Intestinal samples were collected from a local population of feral chickens and administered orally to germfree 3-day-old chicks. Animals were euthanized on days 9 and 18 postinoculation, and intestinal samples were collected and subjected to metagenomic analysis. On day 18, the five most prevalent phyla were (43.03 ± 3.19%), (38.51 ± 2.67%), (6.77 ± 0.7%), (6.38 ± 0.7%), and (2.71 ± 0.55%). Principal-coordinate analysis showed that the day 18 variables clustered more closely than the day 9 variables, suggesting that the microbial communities had changed temporally. The Morista-Horn index values ranged from 0.7 to 1, indicating that the communities in the inoculum and in the day 9 and day 18 samples were more similar than dissimilar. The predicted functional profiles of the microbiomes of the inoculum and the day 9 and day 18 samples were also similar (values of 0.98 to 1). These results indicate that the gnotobiotic chicks stably maintained the phylogenetic diversity and predicted metabolic functionality of the inoculum community. The domestic chicken is the cornerstone of animal agriculture worldwide, with a flock population exceeding 40 billion birds/year. It serves as an economically valuable source of protein globally. The microbiome of poultry has important effects on chicken growth, feed conversion, immune status, and pathogen resistance. The aim of our research was to develop a gnotobiotic chicken model appropriate for the study chicken gut microbiota function. Our experimental model shows that young germfree chicks are able to colonize diverse sets of gut bacteria. Therefore, besides the use of this model to study mechanisms of gut microbiota interactions in the chicken gut, it could be also used for applied aspects such as determining the safety and efficacy of new probiotic strains derived from chicken gut microbiota.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSphere.00035-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437271PMC
March 2019

Probiotic Activity of Enterococcus faecium and Lactococcus lactis Isolated from Thai Fermented Sausages and Their Protective Effect Against Clostridium difficile.

Probiotics Antimicrob Proteins 2020 06;12(2):641-648

Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

Lactic acid bacteria, Enterococcus faecium and Lactococcus lactis, previously isolated from Thai fermented sausages were elucidated their probiotic properties especially in the control of Clostridium difficile 630. Both isolates survived in simulated gastric solution at pH 3 followed in simulated intestinal solution at pH 8. The presence of skimmed milk also helped the bacteria to survive through acidic and alkaline in gastrointestinal conditions. The adhesion properties of both isolates were tested using a human colon adenocarcinoma cell line. The result showed that both isolates exhibited desirable probiotic properties which adhered to Caco-2 cells. The neutralized cell-free supernatant of both isolates demonstrated that no cytotoxicity toward Caco-2 cells vice versa cell-free supernatant of C. difficile 630 toward Caco-2 cell demonstrated high toxicity. The immunomodulation effect in response to bacterial neutralized cell-free supernatant and cell-free supernatant was also studied. The expression level of pro-inflammatory cytokine of Caco-2 cell which are tumor necrosis factor-α and interleukin-8 was evaluated using quantitative reverse transcriptase PCR. Both isolates were able to diminish the expression level of TNF-α and IL-8 induced by the cell-free supernatant of C. difficile 630. Hence, these isolates would be able to improve the gut health through counteracting the C. difficile-associated intestinal inflammation in human cell lines. These results may contribute to the development of the isolates using as probiotics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12602-019-09536-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306037PMC
June 2020

Antimicrobial Effect of Asiatic Acid Against Is Associated With Disruption of Membrane Permeability.

Front Microbiol 2018 7;9:2125. Epub 2018 Sep 7.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

Antibiotic resistance is a major concern in , the causative agent of antibiotic-associated diarrhea. Reduced susceptibility to first- and second-line agents is widespread, therefore various attempts have been made to seek alternative preventive and therapeutic strategies against this pathogen. In this work, the antimicrobial properties of asiatic acid were evaluated against . Asiatic acid displayed substantial inhibitory effects on 19 isolates collected from different sources with minimal inhibitory concentrations ranging from 10 to 20 μg/ml. Time kill analysis and minimal bactericidal concentration revealed potential bactericidal activity of this compound. Asiatic acid induced membrane damages and alterations in morphological ultrastructure in , thereby causing the leakage of intracellular substances. Moreover, asiatic acid also displayed an inhibitory effect on cell motility, but did not interfere with biofilm formation and spore germination. Analysis of drug combination showed no synergistic effect between asiatic acid and vancomycin/metronidazole. Altogether, asiatic acid exhibited strong antimicrobial activity against vegetative cells and could serve as an alternative resource for tackling .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2018.02125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137100PMC
September 2018

Characterization of Bacteriophages Infecting Clinical Isolates of .

Front Microbiol 2018 31;9:1701. Epub 2018 Jul 31.

Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand.

is recognized as a problematic pathogen, causing severe enteric diseases including antibiotic-associated diarrhea and pseudomembranous colitis. The emergence of antibiotic resistant has driven a search for alternative anti-infection modalities. A promising strategy for controlling bacterial infection includes the use of bacteriophages and their gene products. Currently, knowledge of phages active against is still relatively limited by the fact that the isolation of phages for this organism is a technically demanding method since bacterial host themselves are difficult to culture. To isolate and characterize phages specific to , a genotoxic agent, mitomycin C, was used to induce temperate phages from 12 clinical isolates of . Five temperate phages consisting of ΦHR24, ΦHN10, ΦHN16-1, ΦHN16-2, and ΦHN50 were successfully induced and isolated. Spotting assays were performed against a panel of 92 isolates to screen for susceptible bacterial hosts. The results revealed that all the phages obtained in this work displayed a relatively narrow host range of 0-6.5% of the tested isolates. Electron microscopic characterization revealed that all isolated phages contained an icosahedral head connected to a long contractile tail, suggesting that they belonged to the family. Restriction enzyme analysis indicated that these phages possess unique double-stranded DNA genome. Further electron microscopic characterization revealed that the ΦHN10 absorbed to the bacterial surface via attachment to cell wall, potentially interacting with S-layer protein. Bacteriophages isolated from this study could lead to development of novel therapeutic agents and detection strategies for .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2018.01701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079236PMC
July 2018

Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells.

Phytomedicine 2017 Dec 28;36:59-67. Epub 2017 Sep 28.

Department of Anatomy, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. Electronic address:

Background: Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastatic disease, is highly prevalent in Thailand as a consequence of liver fluke infection. Recently, we extracted sulfated galactans (SG) from Gracilaria fisheri (G. fisheri), a south east Asian seaweed, and found it exhibited anti-proliferation effect on CCA cells.

Purpose: In the present study, we evaluated the anti-migration activity of SG on CCA cells and its underlined mechanism.

Methods: CCA cells were treated with SG alone or drugs targeting to epidermal growth factor (EGF) receptor (EGFR) or pretreated with SG prior to incubation with EGF. Anti-migration activity was determined using a scratch wound-healing assay and zymography. Immunofluorescence staining and western blotting were used to investigate EGFR signaling mediators.

Results: Under basal condition, SG reduced the migration rate of CCA, which was correlated with a decrease in the active-form of matrix metalloproteinases-9. SG decreased expression of phosphorylated focal adhesion kinase (FAK), but increased expression of E-cadherin to promote cells stasis. Moreover, phosphorylation of EGFR and extracellular signal-regulated kinases (ERK), known to stimulate growth of cancer cells, was blocked in a comparable way to EGFR inhibitors Cetuximab and Erlotinib. Pretreatment cells with SG attenuated EGF induced phosphorylation of EGFR, ERK and FAK.

Conclusion: This study reveals that SG from G. fisheri retards migration of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on MAPK/ERK signal transduction pathway. Our findings suggest that there may be a therapeutic potential of SG in CCA treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2017.09.014DOI Listing
December 2017

CD2068 potentially mediates multidrug efflux in Clostridium difficile.

Sci Rep 2017 08 30;7(1):9982. Epub 2017 Aug 30.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Clostridium difficile is a major cause of antibiotic-associated diarrhea and the treatment thereof becomes more difficult owing to a rise of multidrug resistant strains. ATP-binding cassette (ABC) transporters are known to play a crucial role in the resistance to multiple antibiotics. In this study, the potential contribution of an ABC transporter in C. difficile multidrug resistance was investigated. The expression level of the cd2068 gene in C. difficile encoding an ABC transporter was up-regulated following the exposure to certain antibiotics compared to the control cells. Heterologous expression of CD2068 in Escherichia coli revealed that it mediated the efflux of fluorescent substrates and conferred resistance to multiple drugs. The CD2068-associated ATPase activity in membrane vesicles was also stimulated by various antibiotics. Furthermore, the insertional inactivation of the cd2068 gene in C. difficile led to a significant increase in susceptibility to antibiotics, which could be genetically complemented, supporting that CD2068 was directly associated to the drug resistance. These results demonstrate the potential role for the ABC transporter CD2068 in the resistance mechanism against multiple drugs in C. difficile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-10155-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577244PMC
August 2017

Microfluidics: innovative approaches for rapid diagnosis of antibiotic-resistant bacteria.

Essays Biochem 2017 02 3;61(1):91-101. Epub 2017 Mar 3.

Department of Biology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

The emergence of antibiotic-resistant bacteria has become a major global health concern. Rapid and accurate diagnostic strategies to determine the antibiotic susceptibility profile prior to antibiotic prescription and treatment are critical to control drug resistance. The standard diagnostic procedures for the detection of antibiotic-resistant bacteria, which rely mostly on phenotypic characterization, are time consuming, insensitive and often require skilled personnel, making them unsuitable for point-of-care (POC) diagnosis. Various molecular techniques have therefore been implemented to help speed up the process and increase sensitivity. Over the past decade, microfluidic technology has gained great momentum in medical diagnosis as a series of fluid handling steps in a laboratory can be simplified and miniaturized on to a small platform, allowing marked reduction of sample amount, high portability and tremendous possibility for integration with other detection technologies. These advantages render the microfluidic system a great candidate to be developed into an easy-to-use sample-to-answer POC diagnosis suitable for application in remote clinical settings. This review provides an overview of the current development of microfluidic technologies for the nucleic acid based and phenotypic-based detections of antibiotic resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/EBC20160059DOI Listing
February 2017

Insights into drug resistance mechanisms in .

Essays Biochem 2017 02 3;61(1):81-88. Epub 2017 Mar 3.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

The incidence of infection has been elevated and becoming common in hospitals worldwide. Although antibiotics usually serve as the primary treatment for bacterial infection including infection, limitations and failures have been evident due to drug resistance. Antibiotic resistance in has been recognized as one of the most important factors to promote the infection and increase the level of severity and the recurrence rate. Several outbreaks in many countries have been linked to the emergence of hypervirulent drug-resistant strains. This pathogen harbours various mechanisms against the actions of antibiotics. The present study highlights three main drug-resistant strategies in including drug inactivation, target modification and efflux pump. Other mechanisms that potentially contribute to drug-resistant traits in this organism are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/EBC20160062DOI Listing
February 2017

Meta-analysis of gene expression profiles identifies differential biomarkers for hepatocellular carcinoma and cholangiocarcinoma.

Tumour Biol 2016 Sep 22;37(9):12755-12766. Epub 2016 Jul 22.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the members of hepatobiliary diseases. Both types of cancer often exert high levels of similarity in terms of phenotypic characteristics, thus leading to difficulties in HCC and CCA differential diagnoses. In this study, a transcriptome meta-analysis was performed on HCC and CCA microarray data to identify differential transcriptome networks and potential biomarkers for HCC and CCA. Raw data from nine gene expression profiling datasets, consisting of 1,185 samples in total, were methodologically compiled and analyzed. To evaluate differentially expressed (DE) genes in HCC and CCA, the levels of gene expression were compared between cancer and its normal counterparts (i.e., HCC versus normal liver and CCA versus normal bile duct) using t test (P < 0.05) and k-fold validation. A total of 226 DE genes were specific to HCC, 249 DE genes specific to CCA, and 41 DE genes in both HCC and CCA. Gene ontology and pathway enrichment analyses revealed different patterns between functional transcriptome networks of HCC and CCA. Cell cycle and glycolysis/gluconeogenesis pathways were exclusively dysregulated in HCC whereas complement and coagulation cascades as well as glycine, serine, and threonine metabolism were prodominantly differentially expressed in CCA. Our meta-analysis revealed distinct dysregulation in transcriptome networks between HCC and CCA. Certain genes in these networks were discussed in the context of HCC and CCA transition, unique characteristics of HCC and CCA, and their potentials as HCC and CCA differential biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13277-016-5186-8DOI Listing
September 2016

Multidrug resistance in Clostridium perfringens isolated from diarrheal neonatal piglets in Thailand.

Anaerobe 2016 Apr 2;38:88-93. Epub 2016 Jan 2.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address:

Clostridium perfringens causes diarrhea in neonatal piglets, thereby affecting commercial swine farming. The objective of this study was to determine the prevalence and characterize antimicrobial resistance in C. perfringens isolated from diarrheal neonatal piglets in Thailand. A total of 260 rectal swab samples were collected from 13 farms and were subjected to C. perfringens isolation. A total of 148 samples were PCR-positive for C. perfringens toxin genes, from which 122 were recovered. All isolates were cpb2-encoding C. perfringens type A and enterotoxin gene negative. Most of the isolates were susceptible to ampicillin, bacitracin, chlorotetracycline, doxycycline, and oxytetracycline with MIC50 values ranging from 0.32 to 8 μg/ml. The high resistance rates were observed for ceftiofur, enrofloxacin, erythromycin, lincomycin, and tylosin. Among resistant isolates, 82% were resistant to more than one type of antibiotics. The distinct pattern of multiple drug resistance in C. perfringens was observed in different regions, potentially reflecting the farm specific usage of these agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anaerobe.2015.12.012DOI Listing
April 2016

Inactivation of Clostridium difficile spores by microwave irradiation.

Anaerobe 2016 Apr 4;38:14-20. Epub 2015 Nov 4.

Center for Emerging and Neglected Infectious Diseases, Mahidol University, Nakhon Pathom, 73170, Thailand; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400 Thailand. Electronic address:

Spores are a potent agent for Clostridium difficile transmission. Therefore, factors inhibiting spores have been of continued interest. In the present study, we investigated the influence of microwave irradiation in addition to conductive heating for C. difficile spore inactivation in aqueous suspension. The spores of 15 C. difficile isolates from different host origins were exposed to conductive heating and microwave irradiation. The complete inhibition of spore viability at 10(7) CFU/ml was encountered following microwave treatment at 800 W for 60 s, but was not observed in the conductive-heated spores at the same time-temperature exposure. The distinct patterns of ultrastructural alterations following microwave and conductive heat treatment were observed and the degree of damages by microwave was in the exposure time-dependent manner. Microwave would therefore be a simple and time-efficient tool to inactivate C. difficile spores, thus reducing the risk of C. difficile transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anaerobe.2015.10.015DOI Listing
April 2016

An Omics Perspective on Molecular Biomarkers for Diagnosis, Prognosis, and Therapeutics of Cholangiocarcinoma.

Int J Genomics 2015 2;2015:179528. Epub 2015 Sep 2.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy arising from the epithelial bile duct. The lack of early diagnostic biomarkers as well as therapeutic measures results in severe outcomes and poor prognosis. Thus, effective early diagnostic, prognostic, and therapeutic biomarkers are required to improve the prognosis and prolong survival rates in CCA patients. Recent advancement in omics technologies combined with the integrative experimental and clinical validations has provided an insight into the underlying mechanism of CCA initiation and progression as well as clues towards novel biomarkers. This work highlights the discovery and validation of molecular markers in CCA identified through omics approaches. The possible roles of these molecules in various cellular pathways, which render CCA carcinogenesis and progression, will also be discussed. This paper can serve as a reference point for further investigations to yield deeper understanding in the complex feature of this disease, potentially leading to better approaches for diagnosis, prognosis, and therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/179528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572471PMC
September 2015