No abstract

Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan® miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-α, IL-1β, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1α were increased, and IFN-γ expression was decreased after radiation, whereas, IL-6, IFN-γ, TNF-α, IL-1β, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1α were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up-regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down-regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment.

Matrix metalloproteinases (MMPs) play a crucial role in developing different types of lung diseases, e.g., pulmonary arterial hypertension (PAH). Green tea polyphenolic catechins such as EGCG and ECG have been shown to ameliorate various types of diseases including PAH. Our present study revealed that among the four green tea catechins (EGCG, ECG, EC, and EGC), EGCG and ECG inhibit pro-/active MMP-2 activities in pulmonary artery smooth muscle cell (PASMC) culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-2 with the green tea catechins by computational methods. In silico analysis revealed a strong interaction of pro-/active MMP-2 with EGCG/ECG, and galloyl group has been observed to be responsible for this interaction. The in silico analysis corroborated our experimental observation that EGCG and ECG are active in preventing both the proMMP-2 and MMP-2 activities. Importantly, these two catechins appeared to be better inhibitors for proMMP-2 in comparison to MMP-2 as revealed by gelatin zymogram and also by molecular docking studies. In many type of cells, activation of proMMP-2 occurs via an increase in the level of MT1-MMP (MMP-14). We, therefore, determined the interactions of MT1-MMP with the green tea catechins by molecular docking analysis. The study revealed a strong interaction of MT1-MMP with EGCG/ECG, and galloyl group has been observed to be responsible for the interaction.

Shigella strains that were untypable by commercially available antisera were isolated from children ,5 years of age with acute diarrhoea in Kolkata. These strains were subsequently identified as Shigella dysenteriae provisional serovar 204/96 (n53), Shigella dysenteriae provisional serovar E23507 (n51), Shigella dysenteriae provisional serovar I9809-73 (n51), Shigella dysenteriae provisional serovar 93-119 (n51), Shigella flexneri provisional serovar 88-893 (n56) and Shigella boydii provisional serovar E16553 (n51). In this study, characterization of those provisional serovars of Shigella was performed with respect to their antimicrobial resistance, plasmids, virulence genes and PFGE profiles. The drug resistant strains (n510) of Shigella identified in this study possessed various antibiotic resistance genetic markers like catA (for chloramphenicol resistance); tetA and tetB (for tetracycline resistance); dfrA1 and sul2 (for co-trimoxazole resistance); aadA1, strA and strB (for streptomycin resistance) and bla OXA-1 (for ampicillin resistance). Class 1 and/or class 2 integrons were present in eight resistant strains. Three study strains were pan-susceptible. A single mutation in the gyrA gene (serine to leucine at codon 83) was present in four quinolone resistant strains. The virulence gene ipaH (invasion plasmid antigen H) was uniformly present in all strains in this study, but the stx (Shiga toxin) and set1 (Shigella enterotoxin 1) genes were absent. Other virulence genes like ial (invasion associated locus) and sen (Shigella enterotoxin 2) were occasionally present. A large plasmid of 212 kb and of incompatibility type IncFIIA was present in the majority of the strains (n510) and diversity was noticed in the smaller plasmid profiles of these strains even within the same provisional serovars. PFGE profile analysis showed the presence of multiple unrelated clones among the isolates of provisional Shigella serovars. To the best of our knowledge, this is the first report on the phenotypic and molecular characterization of provisional serovars of Shigella isolates from Kolkata, India.

Summaryobjectives Shigellosis is a major public health problem, and increasing antimicrobial resistance has complicated its treatment. We report isolation frequency, plasmid profiles and antimicrobial resistance of Shigella subtypes in Kolkata, India, from a prospective hospital-based study.methods Fresh stool or rectal swabs were collected from children (<5 years) attending the Diarrhea Treatment Unit of a governmental paediatric referral hospital in Kolkata. Samples were processed following standard methods over a 7-year period from January 2001 to December 2007.results Of 4478 samples collected, 516 (11.5%) were positive for Shigella spp. S. flexneri (312; 6.9%) was the most frequently isolated serogroup, ranking before S. sonnei (123, 2.7%), S. dysenteriae (48, 1.1%) and S. boydii (33, 0.7%). Although 10 subtypes of S. flexneri were identified, the common ones circulating locally were S. flexneri 2a (179), S. flexneri 6 (38) and S. flexneri 3a (36). Knowledge of Shigella subtypes is important for vaccine development. The majority of Shigella isolates (81.0%) were multidrug (two or more antimicrobial classes) resistant and showed high minimum inhibitory concentration (MIC) with commonly used drugs like ampicillin, tetracycline, co-trimoxazole and nalidixic acid. conclusion Long-term surveillance of Shigellae and their antimicrobial resistance are mandatory in endemic areas to formulate treatment policy until any suitable candidate vaccine is available to control the disease.