Enteroaggregative Escherichia coli (EAEC) is an evolving enteric pathogen that causes acute and chronic diarrhea in developed and industrialized nations in children. EAEC epidemiology and the importance of atypical EAEC (aEAEC) isolation in childhood diarrhea are not well documented in the Indian setting. A comparative analysis was undertaken to evaluate virulence, phylogeny, and antibiotic sensitivity among typical tEAEC versus aEAEC. A total of 171 EAEC isolates were extracted from a broad surveillance sample of diarrheal (N = 1210) and healthy children (N = 550) across North India. Polymerase chain reaction (PCR) for the aggR gene (master regulator gene) was conducted to differentiate tEAEC and aEAEC. For 21 virulence genes, we used multiplex PCR to classify possible virulence factors among these strains. Phylogenetic classes were identified by a multiplex PCR for chuA, yjaA, and a cryptic DNA fragment, TspE4C2. Antibiotic susceptibility was conducted by the disc diffusion method as per CLSI guidelines. EAEC was associated with moderate to severe diarrhea in children. The prevalence of EAEC infection (11.4%) was higher than any other DEC group (p = 0.002). tEAEC occurrence in the diarrheal group was higher than in the control group (p = 0.0001). tEAEC strain harbored more virulence genes than aEAEC. astA, aap, and aggR genes were most frequently found in the EAEC from the diarrheal population. Within tEAEC, this gene combination was present in more than 50% of strains. Also, 75.8% of EAEC strains were multidrug-resistant (MDR). Phylogroup D (43.9%) and B1 (39.4%) were most prevalent in the diarrheal and control group, respectively. Genetic analysis revealed EAEC variability; the comparison of tEAEC and aEAEC allowed us to better understand the EAEC virulence repertoire. Further microbiological and epidemiological research is required to examine the pathogenicity of not only typical but also atypical EAEC.

Background:Lung cancer is a leading cause of cancer death. There has been found a substantial gap in the understanding of lung cancer genesis at the molecular level. We developed urethane (ethyl carbamate) induced lung tumor mice model to understand the mechanism and molecules involved in the cancer genesis. There might be many molecules involved, but we subsequently emphasized here the study of alternation in the expression of NF-κB, Stat3, and inflammatory cytokines interleukin-1β and interleukin-6 to hypothesize that the microenvironment created by these molecules is promoting tumor formation.Materials and Methods:7–8 week old Balb/c mice of either sex were given intraperitoneal (i.p.) injection of urethane (1g/kgbw) for eight consecutive weeks. Histopathological analysis was done to detect abnormality or invasions occurred in the lung tissues. Automated cell counter was used to count the number of inflammatory cells. The expression of NF-κB, Stat3, and IL-1β was observed at translational level by western blot, while the expression of IL-1β and IL-6 was observed at transcriptional level by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) method. Secretion of IL-1β and IL-6 in the blood was measured by enzyme-linked immunosorbent assay (ELISA) method at different time intervals.Results:Histopathological analysis showed various lung cancer stages hyperplasia, atypical adenomatous hyperplasia, and adenocarcinoma. Increased population of inflammatory cells, persistant expression of NF-κB, Stat3, pStat3, and IL-1β at translational level, while at transcriptional level constitutive enhanced expression of IL-1β and IL-6 followed by increased secretion of IL-1β and IL-6 in the blood were observed in urethane-injected mice in comparison to phosphate buffer saline (PBS) injected mice at 12, 24, and 36 weeksConclusions:Overexpression of key molecules such as NF-κB, Stat3, pStat3, IL-1β, and IL-6 might have caused chronic inflammation, leading to the progression of lung cancer.

Polyphenolic compounds of Achyranthes aspera (PCA) extract is evaluated for anti-cancerous and cytokine based immunomodulatory effects. The PCA extract contains known components of phenolic acid and flavonoids such as mixture of quinic acid, chlorogenic acid, kaempferol, quercetin and chrysin along with many unknown components. PCA has been orally feed to urethane (ethyl carbamate) primed lung cancerous mice at a dosage of 100 mg/kg body weight for 30 consecutive days. 100 mg powder of A. aspera contains 2.4 mg phenolic acid and 1.1 mg flavonoid (2:1 ratio). Enhanced activities and expression of antioxidant enzymes GST, GR, CAT, SOD, while down regulated expression and activation of LDH enzymes in PCA feed urethane primed lung cancerous tissues as compared to PCA non-feed urethane primed lung cancerous tissues were observed. PCA feed urethane primed lung tissues showed down regulated expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α along with TFs, NF-κB and Stat3 while the expression of pro-apoptotic proteins Bax and p53 were enhanced in PCA feed urethane primed lung tissues. FTIR and CD spectroscopy data revealed that PCA resisted the urethane mediated conformational changes of DNA which is evident by the shift in guanine and thymine bands in FTIR from 1,708 to 1,711 cm(-1) and 1,675 to 1,671 cm(-1), respectively in PCA feed urethane primed lung cancerous tissues DNA in comparison to urethane primed lung cancerous tissues DNA. The present study suggests that PCA components have synergistic anti-cancerous and cytokine based immunomodulatory role and DNA conformation restoring effects. However, more research is required to show the effects of each component separately and in combination for effective therapeutic use to cure and prevent lung cancer including other cancers.

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