Accumulated evidence suggests a physiological relationship between the transcription factor NRF3 (NFE2L3) and cancers. Under physiological conditions, NRF3 is repressed by its endoplasmic reticulum (ER) sequestration. In response to unidentified signals, NRF3 enters the nucleus and modulates gene expression. However, molecular mechanisms underlying the nuclear translocation of NRF3 and its target gene in cancer cells remain poorly understood. We herein report that multiple regulation of NRF3 activities controls cell proliferation. Our analyses reveal that under physiological conditions, NRF3 is rapidly degraded by the ER-associated degradation (ERAD) ubiquitin ligase HRD1 and valosin-containing protein (VCP) in the cytoplasm. Furthermore, NRF3 is also degraded by β-TRCP, an adaptor for the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase in the nucleus. The nuclear translocation of NRF3 from the ER requires the aspartic protease DNA-damage inducible 1 homolog 2 (DDI2) but does not require inhibition of its HRD1-VCP-mediated degradation. Finally, NRF3 mediates gene expression of the cell cycle regulator U2AF homology motif kinase 1 (UHMK1) for cell proliferation. Collectively, our study provides us many insights into the molecular regulation and biological function of NRF3 in cancer cells.
In developing countries, the occurrence of antibiotic resistance is increasing day by day and antibiotic resistant microorganisms are being found in almost every environmental setting. Plasmids are considered as the main vector in the procurement and propagation of antibiotic resistance in many microorganisms such as Escherichia coli ( E. coli). The goal of this study was to examine the antibiotic resistance and screening of plasmid in E. coli strains which were previously identified from human sewage samples. During this study antibiotic susceptibility of E. coli isolates were determined by Kirby-Bauer disk diffusion method against 5 antibiotics (ampicilin, ceftriaxone, amoxicillin, ciprofloxacin, azithromycin). Furthermore, plasmid extraction of each isolate was done according to the protocol of FavorPrepTMPlasmid Mini Kit and plasmid profiling was done by agarose gel electrophoresis. In antibiotic sensitivity test, all E. coli strains showed resistance to ampicilin, amoxicillin, and ceftriaxone. In the plasmid profiling, it was revealed that all the isolates of E. coli harbored plasmids. The plasmid sizes ranged from approximately 1.5 to 15 kb. The findings of this study prove the consequences of antibiotic resistance as well as relationship of plasmid with antibiotic resistance which necessitates proper surveillance on antibiotic usage in the developing countries.
Antibiotic-resistance genes carried by coliforms in drinking water is a concerning issue for public health in Bangladesh. This research was carried out to identify coliforms in drinking water and to understand the importance of the int1 gene of coliforms in the spread of resistance to bacterial antibiotics through consumption of contaminated water. A total of 31 drinking water samples were collected from restaurants ( n = 18), health center ( n = 9), and residences ( n = 4) located in Chattogram City, Bangladesh. The isolation and identification of coliforms was performed on selective media with a combination of biochemical and molecular analysis. PCR amplification of the LacZ, uidA and int1 genes was carried out for the identification of the coliform and fecal coliform and antibiotic resistant gene, respectively. Antimicrobial susceptibility test was performed according to the Kirby-Bauer disk diffusion method with McFarland standard against three selective antibiotics including co-trimoxazole, ciprofloxacin, and ampicillin. Of 31 drinking water samples, coliforms were detected within 32% ( n = 10) of the water samples, nine samples were collected in restaurants and one sample in a residence. But no coliform was detected in the drinking water of the health center. Among the identified coliforms, the prevalence of fecal coliforms and the int1 gene was 60% ( n = 6) and 40% ( n = 4), relatively. All isolates containing the int1 microbial-resistance gene were resistant to ampicillin.This study shows that drinking water consumed in different restaurants located in Chattogram, Bangladesh is contaminated by antibiotic-resistant gene bearing coliforms that not only increase the risk of water-borne disease, but also may be the major cause of antibiotic resistance transmission in this part of Bangladesh.
Typhoid is a major public health concern. Even though antibiotics are usually used to treat typhoid fever, the spread of multi drug resistant Salmonella typhi is making antibiotics much less effective. This study was conducted to assess the prevalence of multidrug-resistant Salmonella typhi from the clinical samples. During this study, 154 blood samples of suspected typhoid patients were collected from the hospital and diagnostic center located in Chattogram City, Bangladesh. Isolation and identification of Salmonella typhi was done by both biochemical tests. PCR analysis was also done for the confirmation of biochemical result. Antimicrobial susceptibility test was performed according to the Kirby-Bauer disk diffusion method against ampicillin, chloramphenicol, cefepime, cotrimoxazole, ceptriaxone, ciprofloxacin, nalidixic acid, and azithtomycin. Out of 154, 21 (13.64%) isolates were identified as Salmonella typhi and the prevalence of typhoid in Chattogram, Bangladesh was 13.64% (n = 21). It was also found that children under the age of 5 are the more vulnerable target of Salmonella typhi infection. Antibiotic resistance profiling revealed 85% isolates were Multi-Drug Resistant (MDR) and highest resistance was found in case of Nalidixic acid. Although, most of the isolated Salmonella typhi were MDR, first generation antibiotics Co-trimoxazile, Chloramphenicol, and Ampicillin were found effective against Salmonella typhi.
Antibiotic resistance due to misuses of antibiotics is currently became potent threat for treating patients suffering from infectious diseases in Bangladesh. It is the high time to develop some alternative placebo for the treatment of infectious diseases especially in Bangladesh. Probiotic especially could be that alternative choice of treatment against infection. The present study was undertaken to examine the potentiality of as probiotic against .During this study, four poor hygienic areas around Chattogram City, Bangladesh were selected through survey and then human stool samples were collected. Isolation and identification of were done with a combination of microbiological and PCR analysis. Probiotic activity of isolated against was determined by co-culture test. Total eight isolates were identified as by microbiological and biochemical test. All the isolates were also confirmed as bacteria, coliform as well as fecal coliform through PCR. In the probiotic activity test, all the identified isolates except one showed significant result as probiotic. This research identified the potentiality of as probiotic to treat shigellosis in Bangladesh. The outcomes of this study might function as a strong background to develop as probiotic against infection in Bangladesh.
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